WO2024263856A1

WO2024263856A1 - Oral formulations comprising avatrombopag and related uses

Info

Publication number: WO2024263856A1
Application number: PCT/US2024/034931
Authority: WO
Inventors: Brian D. JAMIESON
Original assignee: AkaRx Inc
Current assignee: AkaRx Inc
Priority date: 2023-06-23
Filing date: 2024-06-21
Publication date: 2024-12-26
Anticipated expiration: 2025-12-23
Also published as: CO2025015967A2; AU2024311302A1

Abstract

The present disclosure provides pharmaceutical formulation comprising avatrombopag, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.

Description

ORAL FORMULATIONS COMPRISING AVATROMBOPAG AND RELATED USES

RELATED APPLICATIONS

[0001] This application claims the benefit of and priority to U.S. Provisional Application No. 63/509,862, filed June 23, 2023, the contents of which are incorporated herein by reference in their entireties.

BACKGROUND

[0002] Thrombocytopenia is a potentially serious condition characterized by a deficiency of platelets in the circulatory system. It is associated with an increased risk of bleeding, particularly from small capillaries, resulting in thrombocytopenic purpura. The causes of thrombocytopenia include decreases in platelet production in the bone marrow and decreases in platelet survival in the blood. There are specific disease-related thrombocytopenias, such as immune (idiopathic) thrombocytopenic purpura (ITP) and thrombocytopenias caused by the indirect effect of other diseases on the bone marrow, including malignancies and infections such as hepatitis. Currently, management of thrombocytopenia is primarily based on platelet transfusion. Despite the effectiveness of transfusion, approximately 30% of transfusions are associated with serious complications, including alloimmunization, febrile and allergic reactions, circulatory overload, acute pulmonary injury and bacterial or viral infections. In the 15 to 25% of patients who require repeated platelet transfusions, the platelet response is inadequate due to human leukocyte antigen (HLA) alloimmunization. Therefore, a safe thrombopoietic agent that can lessen or eliminate the need for platelet transfusion would benefit patient health and could significantly lower health-care costs. There is thus a need for novel formulations of thrombopoietic agents.

SUMMARY

[0003] The present disclosure provides solid particle formulations, comprising: avatrombopag or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.

[0004] In certain aspects, the present disclosure provides methods of preparing a. dispersed particle formulation, comprising dispersing the particle formulation disclosed herein in a media. [0005] In certain aspects, the present disclosure provides dispersed particle formulations, being prepared by the method disclosed herein. [0006] In certain aspects, the present disclosure provides methods of treating or preventing a disease in a subject, comprising administering to the subject the dispersed particle formulation disclosed herein. [0007] In certain aspects, the present disclosure provides uses of the dispersed particle formulation disclosed herein in the manufacture of a medicament for treating or preventing a disease in a subject. [0008] In certain aspects, the present disclosure provides the dispersed particle formulation disclosed herein for use in treating or preventing a disease in a subject. [0009] In certain aspects, the present disclosure provides methods of treating a disease in a subject, comprising administering to the subject the dispersed particle formulation disclosed herein. [0010] In certain aspects, the present disclosure provides uses of the dispersed particle formulation disclosed herein in the manufacture of a medicament for treating a disease in a subject. [0011] In certain aspects, the present disclosure provides the dispersed particle formulation disclosed herein for use in treating a disease in a subject. [0012] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. In the specification, the singular forms also include the plural unless the context clearly dictates otherwise. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, suitable methods and materials are described below. All publications, patent applications, patents and other references mentioned herein are incorporated by reference. The references cited herein are not admitted to be prior art to the claimed invention. In the case of conflict, the present specification, including definitions, will control. In addition, the materials, methods and examples are illustrative only and are not intended to be limiting. In the case of conflict between the chemical structures and names of the compounds disclosed herein, the chemical structures will control. [0013] Other features and advantages of the disclosure will be apparent from the following detailed description and claims. BRIEF DESCRIPTION OF FIGURES [0014] FIG.1 is a graph that illustrates the dissolution profiles for capsule of avatrombopag powder for oral suspension, 10 mg. [0015] FIG.2 is a graph that illustrates the dissolution profiles of capsules of avatrombopag for oral suspension, 10 mg from development and clinical batches. [0016] FIG.3 is a flow chart that illustrates the manufacturing process. [0017] FIG.4 is a bar graph that shows the particle size distribution of avatrombopag granules. DETAILED DESCRIPTION [0018] As used herein, “avatrombopag” refers to a compound having the following structure:

which may be identified by CAS No.570406-98-3, and/or by IUPAC name 1-[3-Chloro-5-[[4- (4-chlorothiophen-2-yl)-5-(4-cyclohexylpiperazin-1-yl)-1,3-thiazol-2-yl]carbamoyl]pyridin- 2-yl]piperidine-4-carboxylic acid. [0019] Without wishing to be bound by theory, it is noted that a tablet formulation of avatrombopag may not be appropriate for a subject who cannot or will not swallow a tablet. Further, an IV route of administration of avatrombopag may not be a preferred route for out- patient use and may be difficult to develop due to solubility. Therefore, the formulation of the present disclosure may be an age-appropriate formulation of avatrombopag that could allow for administration of avatrombopag to a subject between the ages of 1 month and <18 years who cannot swallow tablets, or a subject of any age who is not able to swallow a tablet, or is unwilling to swallow a tablet. [0020] In certain aspects, the present disclosure provides solid particle formulations, comprising: avatrombopag, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients. [0021] In certain embodiments, the formulation is substantially free from lactose. Solid Particle [0022] In certain embodiments, the solid particle is a powder or granule. [0023] In certain embodiments, the solid particle is a granule. [0024] In certain embodiments, the population of solid particles has an average diameter of about 100 µm to about 1000 µm. In certain embodiments, the population of solid particles has an average diameter of about 100 µm to about 900 µm. In certain embodiments, the population of solid particles has an average diameter of about 100 µm to about 800 µm. In certain embodiments, the population of solid particles has an average diameter of about 100 µm to about 700 µm. In certain embodiments, the population of solid particles has an average diameter of about 100 µm to about 600 µm. In certain embodiments, the population of solid particles has an average diameter of about 100 µm to about 500 µm. In certain embodiments, the population of solid particles has an average diameter of about 100 µm to about 400 µm. In certain embodiments, the population of solid particles has an average diameter of about 100 µm to about 300 µm. In certain embodiments, the population of solid particles has an average diameter of about 100 µm to about 200 µm. In certain embodiments, the population of solid particles has an average diameter of about 200 µm to about 1000 µm. In certain embodiments, the population of solid particles has an average diameter of about 200 µm to about 900 µm. In certain embodiments, the population of solid particles has an average diameter of about 200 µm to about 800 µm. In certain embodiments, the population of solid particles has an average diameter of about 200 µm to about 700 µm. In certain embodiments, the population of solid particles has an average diameter of about 200 µm to about 600 µm. In certain embodiments, the population of solid particles has an average diameter of about 200 µm to about 500 µm. In certain embodiments, the population of solid particles has an average diameter of about 200 µm to about 400 µm. In certain embodiments, the population of solid particles has an average diameter of about 200 µm to about 300 µm. In certain embodiments, the population of solid particles has an average diameter of about 300 µm to about 1000 µm. In certain embodiments, the population of solid particles has an average diameter of about 300 µm to about 900 µm. In certain embodiments, the population of solid particles has an average diameter of about 300 µm to about 800 µm. In certain embodiments, the population of solid particles has an average diameter of about 300 µm to about 700 µm. In certain embodiments, the population of solid particles has an average diameter of about 300 µm to about 600 µm. In certain embodiments, the population of solid particles has an average diameter of about 300 µm to about 500 µm. In certain embodiments, the population of solid particles has an average diameter of about 300 µm to about 400 µm. In certain embodiments, the population of solid particles has an average diameter of about 400 µm to about 1000 µm. In certain embodiments, the population of solid particles has an average diameter of about 400 µm to about 900 µm. In certain embodiments, the population of solid particles has an average diameter of about 400 µm to about 800 µm. In certain embodiments, the population of solid particles has an average diameter of about 400 µm to about 700 µm. In certain embodiments, the population of solid particles has an average diameter of about 400 µm to about 600 µm. In certain embodiments, the population of solid particles has an average diameter of about 400 µm to about 500 µm. In certain embodiments, the population of solid particles has an average diameter of about 500 µm to about 1000 µm. In certain embodiments, the population of solid particles has an average diameter of about 500 µm to about 900 µm. In certain embodiments, the population of solid particles has an average diameter of about 500 µm to about 800 µm. In certain embodiments, the population of solid particles has an average diameter of about 500 µm to about 700 µm. In certain embodiments, the population of solid particles has an average diameter of about 500 µm to about 600 µm. In certain embodiments, the population of solid particles has an average diameter of about 600 µm to about 1000 µm. In certain embodiments, the population of solid particles has an average diameter of about 600 µm to about 900 µm. In certain embodiments, the population of solid particles has an average diameter of about 600 µm to about 800 µm. In certain embodiments, the population of solid particles has an average diameter of about 600 µm to about 700 µm. In certain embodiments, the population of solid particles has an average diameter of about 700 µm to about 1000 µm. In certain embodiments, the population of solid particles has an average diameter of about 700 µm to about 900 µm. In certain embodiments, the population of solid particles has an average diameter of about 700 µm to about 800 µm. In certain embodiments, the population of solid particles has an average diameter of about 800 µm to about 1000 µm. In certain embodiments, the population of solid particles has an average diameter of about 800 µm to about 900 µm. In certain embodiments, the population of solid particles has an average diameter of about 900 µm to about 1000 µm. [0025] In certain embodiments, the population of solid particles has an average diameter of about 300 µm. In certain embodiments, the population of solid particles has an average diameter of about 350 µm. In certain embodiments, the population of solid particles has an average diameter of about 400 µm. In certain embodiments, the population of solid particles has an average diameter of about 450 µm. In certain embodiments, the population of solid particles has an average diameter of about 500 µm. In certain embodiments, the population of solid particles has an average diameter of about 550 µm. In certain embodiments, the population of solid particles has an average diameter of about 600 µm. In certain embodiments, the population of solid particles has an average diameter of about 650 µm. In certain embodiments, the population of solid particles has an average diameter of about 700 µm. In certain embodiments, the population of solid particles has an average diameter of about 750 µm. In certain embodiments, the population of solid particles has an average diameter of about 800 µm. In certain embodiments, the population of solid particles has an average diameter of about 850 µm. [0026] In certain embodiments, the population of solid particles has a bulk density of about 0.54 g/mL to about 0.78 g/mL. In certain embodiments, the population of solid particles has a bulk density of about 0.54 g/mL to about 0.74 g/mL. In certain embodiments, the population of solid particles has a bulk density of about 0.54 g/mL to about 0.70 g/mL. In certain embodiments, the population of solid particles has a bulk density of about 0.54 g/mL to about 0.66 g/mL. In certain embodiments, the population of solid particles has a bulk density of about 0.54 g/mL to about 0.62 g/mL. In certain embodiments, the population of solid particles has a bulk density of about 0.54 g/mL to about 0.58 g/mL. In certain embodiments, the population of solid particles has a bulk density of about 0.58 g/mL to about 0.78 g/mL. In certain embodiments, the population of solid particles has a bulk density of about 0.58 g/mL to about 0.74 g/mL. In certain embodiments, the population of solid particles has a bulk density of about 0.58 g/mL to about 0.70 g/mL. In certain embodiments, the population of solid particles has a bulk density of about 0.58 g/mL to about 0.66 g/mL. In certain embodiments, the population of solid particles has a bulk density of about 0.58 g/mL to about 0.62 g/mL. In certain embodiments, the population of solid particles has a bulk density of about 0.62 g/mL to about 0.78 g/mL. In certain embodiments, the population of solid particles has a bulk density of about 0.62 g/mL to about 0.74 g/mL. In certain embodiments, the population of solid particles has a bulk density of about 0.62 g/mL to about 0.70 g/mL. In certain embodiments, the population of solid particles has a bulk density of about 0.62 g/mL to about 0.66 g/mL. In certain embodiments, the population of solid particles has a bulk density of about 0.66 g/mL to about 0.78 g/mL. In certain embodiments, the population of solid particles has a bulk density of about 0.66 g/mL to about 0.74 g/mL. In certain embodiments, the population of solid particles has a bulk density of about 0.66 g/mL to about 0.70 g/mL. In certain embodiments, the population of solid particles has a bulk density of about 0.70 g/mL to about 0.78 g/mL. In certain embodiments, the population of solid particles has a bulk density of about 0.70 g/mL to about 0.74 g/mL. In certain embodiments, the population of solid particles has a bulk density of about 0.74 g/mL to about 0.78 g/mL. [0027] In certain embodiments, the population of solid particles has a bulk density of about 0.58 g/mL. In certain embodiments, the population of solid particles has a bulk density of about 0.60 g/mL. In certain embodiments, the population of solid particles has a bulk density of about 0.61 g/mL. In certain embodiments, the population of solid particles has a bulk density of about 0.62 g/mL. In certain embodiments, the population of solid particles has a bulk density of about 0.63 g/mL. In certain embodiments, the population of solid particles has a bulk density of about 0.64 g/mL. In certain embodiments, the population of solid particles has a bulk density of about 0.65 g/mL. In certain embodiments, the population of solid particles has a bulk density of about 0.66 g/mL. In certain embodiments, the population of solid particles has a bulk density of about 0.68 g/mL. In certain embodiments, the population of solid particles has a bulk density of about 0.70 g/mL. In certain embodiments, the population of solid particles has a bulk density of about 0.72 g/mL. Avatrombopag [0028] In certain embodiments, the formulation comprises avatrombopag. [0029] In certain embodiments, the formulation comprises a pharmaceutically acceptable salt of avatrombopag. [0030] In certain embodiments, the pharmaceutically acceptable salt of avatrombopag is avatrombopag maleate salt. [0031] In certain embodiments, the pharmaceutically acceptable salt of avatrombopag is avatrombopag monomaleate salt. [0032] In certain embodiments, the formulation comprises avatrombopag maleate salt. [0033] In certain embodiments, the formulation comprises avatrombopag monomaleate salt. [0034] In certain embodiments, the formulation comprises a population of solid particles of avatrombopag or a pharmaceutically acceptable salt thereof. [0035] In certain embodiments, the formulation comprises a population of solid particles of avatrombopag. [0036] In certain embodiments, the formulation comprises a population of solid particles of the pharmaceutically acceptable salt of avatrombopag. [0037] In certain embodiments, the formulation comprises a population of solid particles of avatrombopag maleate salt. [0038] In certain embodiments, the formulation comprises a population of solid particles of monomaleate salt. [0039] In certain embodiments, the avatrombopag or a pharmaceutically acceptable salt thereof is present in an amount ranging from about 5.0% w/w to about 18.0% w/w. In certain embodiments, the avatrombopag or a pharmaceutically acceptable salt thereof is present in an amount ranging from about 5.0% w/w to about 16.0% w/w. In certain embodiments, the avatrombopag or a pharmaceutically acceptable salt thereof is present in an amount ranging from about 5.0% w/w to about 14.0% w/w. In certain embodiments, the avatrombopag or a pharmaceutically acceptable salt thereof is present in an amount ranging from about 5.0% w/w to about 12.0% w/w. In certain embodiments, the avatrombopag or a pharmaceutically acceptable salt thereof is present in an amount ranging from about 5.0% w/w to about 10.0% w/w. In certain embodiments, the avatrombopag or a pharmaceutically acceptable salt thereof is present in an amount ranging from about 5.0% w/w to about 8.0% w/w. [0040] In certain embodiments, the avatrombopag or a pharmaceutically acceptable salt thereof is present in an amount ranging from about 7.0% w/w to about 18.0% w/w. In certain embodiments, the avatrombopag or a pharmaceutically acceptable salt thereof is present in an amount ranging from about 7.0% w/w to about 16.0% w/w. In certain embodiments, the avatrombopag or a pharmaceutically acceptable salt thereof is present in an amount ranging from about 7.0% w/w to about 14.0% w/w. In certain embodiments, the avatrombopag or a pharmaceutically acceptable salt thereof is present in an amount ranging from about 7.0% w/w to about 12.0% w/w. In certain embodiments, the avatrombopag or a pharmaceutically acceptable salt thereof is present in an amount ranging from about 7.0% w/w to about 10.0% w/w. In certain embodiments, the avatrombopag or a pharmaceutically acceptable salt thereof is present in an amount ranging from about 7.0% w/w to about 8.0% w/w. [0041] In certain embodiments, the avatrombopag or a pharmaceutically acceptable salt thereof is present in an amount ranging from about 9.0% w/w to about 18.0% w/w. In certain embodiments, the avatrombopag or a pharmaceutically acceptable salt thereof is present in an amount ranging from about 9.0% w/w to about 16.0% w/w. In certain embodiments, the avatrombopag or a pharmaceutically acceptable salt thereof is present in an amount ranging from about 9.0% w/w to about 14.0% w/w. In certain embodiments, the avatrombopag or a pharmaceutically acceptable salt thereof is present in an amount ranging from about 9.0% w/w to about 12.0% w/w. In certain embodiments, the avatrombopag or a pharmaceutically acceptable salt thereof is present in an amount ranging from about 9.0% w/w to about 10.0% w/w. [0042] In certain embodiments, the avatrombopag or a pharmaceutically acceptable salt thereof is present in an amount ranging from about 11.0% w/w to about 18.0% w/w. In certain embodiments, the avatrombopag or a pharmaceutically acceptable salt thereof is present in an amount ranging from about 11.0% w/w to about 16.0% w/w. In certain embodiments, the avatrombopag or a pharmaceutically acceptable salt thereof is present in an amount ranging from about 11.0% w/w to about 14.0% w/w. In certain embodiments, the avatrombopag or a pharmaceutically acceptable salt thereof is present in an amount ranging from about 11.0% w/w to about 12.0% w/w. [0043] In certain embodiments, avatrombopag is present in an amount of about 10.0% w/w, or avatrombopag monomaleate is present in an amount of about 11.8% w/w. Pharmaceutically Acceptable Excipients [0044] In certain embodiments, the solid particle formulation comprises one or more pharmaceutically acceptable excipients. Diluent [0045] In certain embodiments, the formulation comprises a diluent. [0046] In some embodiments, the diluent is selected from of lactose, sucrose (e.g., Dipac®), dextrose, dextrates, maltodextrin, mannitol, xylitol (e.g., Xylitab®), sorbitol, cyclodextrins, calcium phosphate, calcium sulfate, starches, modified starches, cellulose, microcrystalline cellulose (e.g., Avicel®), microcellulose, and talc. [0047] In certain embodiments, the diluent comprises microcrystalline cellulose. In certain embodiments, the diluent comprises mannitol. In certain embodiments, the diluent comprises microcrystalline cellulose and mannitol. [0048] In certain embodiments, the diluent is present in an amount ranging from about 66.0 w/w% to about 86.0 w/w%. In certain embodiments, the diluent is present in an amount ranging from about 66.0 w/w% to about 82.0 w/w%. In certain embodiments, the diluent is present in an amount ranging from about 66.0 w/w% to about 78.0 w/w%. In certain embodiments, the diluent is present in an amount ranging from about 66.0 w/w% to about 74.0 w/w%. In certain embodiments, the diluent is present in an amount ranging from about 66.0 w/w% to about 70.0 w/w%. In certain embodiments, the diluent is present in an amount ranging from about 70.0 w/w% to about 86.0 w/w%. In certain embodiments, the diluent is present in an amount ranging from about 70.0 w/w% to about 82.0 w/w%. In certain embodiments, the diluent is present in an amount ranging from about 70.0 w/w% to about 78.0 w/w%. In certain embodiments, the diluent is present in an amount ranging from about 70.0 w/w% to about 74.0 w/w%. In certain embodiments, the diluent is present in an amount ranging from about 74.0 w/w% to about 86.0 w/w%. In certain embodiments, the diluent is present in an amount ranging from about 74.0 w/w% to about 82.0 w/w%. In certain embodiments, the diluent is present in an amount ranging from about 74.0 w/w% to about 78.0 w/w%. In certain embodiments, the diluent is present in an amount ranging from about 78.0 w/w% to about 86.0 w/w%. In certain embodiments, the diluent is present in an amount ranging from about 78.0 w/w% to about 82.0 w/w%. [0049] In certain embodiments, the diluent is present in an amount of about 66.0 w/w%. In certain embodiments, the diluent is present in an amount of about 68.0 w/w%. In certain embodiments, the diluent is present in an amount of about 70.0 w/w%. In certain embodiments, the diluent is present in an amount of about 72.0 w/w%. In certain embodiments, the diluent is present in an amount of about 74.0 w/w%. In certain embodiments, the diluent is present in an amount of about 76.0 w/w%. In certain embodiments, the diluent is present in an amount of about 78.0 w/w%. In certain embodiments, the diluent is present in an amount of about 80.0 w/w%. In certain embodiments, the diluent is present in an amount of about 82.0 w/w%. In certain embodiments, the diluent is present in an amount of about 84.0 w/w%. In certain embodiments, the diluent is present in an amount of about 86.0 w/w%. [0050] In certain embodiments, the diluent is present in an amount of about 77.2±20.0 w/w%, about 77.2±15.0 w/w%, about 77.2±10.0 w/w%, about 77.2±9.0 w/w%, about 77.2±8.0 w/w%, about 77.2±7.0 w/w%, about 77.2±6.0 w/w%, about 77.2±5.0 w/w%, about 77.2±4.0 w/w%, about 77.2±3.0 w/w%, about 77.2±2.0 w/w%, or about 77.2±1.0 w/w% (e.g., about 77.2 w/w%). [0051] In certain embodiments, the diluent comprises microcrystalline cellulose, and the microcrystalline cellulose is present in an amount of about 28.0% w/w. [0052] In certain embodiments, the diluent comprises mannitol, and the mannitol is present in an amount of about 49% w/w. [0053] In certain embodiments, the diluent comprises microcrystalline cellulose and mannitol, the microcrystalline cellulose is present in an amount of about 28.0% w/w, and the mannitol is present in an amount of about 49% w/w. Binder [0054] In certain embodiments, the formulation comprises a binder. [0055] In certain embodiments, the binder is selected from polyvinylpyrrolidone (PVP) (e.g., PVP Kl 5, PVP K19, PVP K25, PVP K30, Povidone® CL, Kollidon® CL, Polyplasdone® XL- 10, and Povidone® K-12), cross-linked polyvinyl N-pyrrolidone (crospovidone), hydroxy propyl cellulose (HPC), hydroxy propyl methyl cellulose (HPMC), microcrystalline cellulose (MCC), sodium carboxy methyl cellulose, methylcellulose, lactose, sucrose, sorbitol, xylitol, mannitol, starch, sodium alginate, gelatin, and polyethylene glycol (PEG). [0056] In certain embodiments, the binder comprises crospovidone. [0057] In certain embodiments, the binder is present in an amount ranging from about 2.0 w/w% to about 8.0 w/w%. In certain embodiments, the binder is present in an amount ranging from about 2.0 w/w% to about 7.0 w/w%. In certain embodiments, the binder is present in an amount ranging from about 2.0 w/w% to about 6.0 w/w%. In certain embodiments, the binder is present in an amount ranging from about 2.0 w/w% to about 5.0 w/w%. In certain embodiments, the binder is present in an amount ranging from about 2.0 w/w% to about 4.0 w/w%. In certain embodiments, the binder is present in an amount ranging from about 2.0 w/w% to about 3.0 w/w%. In certain embodiments, the binder is present in an amount ranging from about 3.0 w/w% to about 8.0 w/w%. In certain embodiments, the binder is present in an amount ranging from about 3.0 w/w% to about 7.0 w/w%. In certain embodiments, the binder is present in an amount ranging from about 3.0 w/w% to about 6.0 w/w%. In certain embodiments, the binder is present in an amount ranging from about 3.0 w/w% to about 5.0 w/w%. In certain embodiments, the binder is present in an amount ranging from about 3.0 w/w% to about 4.0 w/w%. In certain embodiments, the binder is present in an amount ranging from about 4.0 w/w% to about 8.0 w/w%. In certain embodiments, the binder is present in an amount ranging from about 4.0 w/w% to about 7.0 w/w%. In certain embodiments, the binder is present in an amount ranging from about 4.0 w/w% to about 6.0 w/w%. In certain embodiments, the binder is present in an amount ranging from about 4.0 w/w% to about 5.0 w/w%. In certain embodiments, the binder is present in an amount ranging from about 5.0 w/w% to about 8.0 w/w%. In certain embodiments, the binder is present in an amount ranging from about 5.0 w/w% to about 7.0 w/w%. In certain embodiments, the binder is present in an amount ranging from about 5.0 w/w% to about 6.0 w/w%. In certain embodiments, the binder is present in an amount ranging from about 6.0 w/w% to about 8.0 w/w%. In certain embodiments, the binder is present in an amount ranging from about 6.0 w/w% to about 7.0 w/w%. [0058] In certain embodiments, the binder is present in an amount of about 2.0 w/w%. In certain embodiments, the binder is present in an amount of about 2.5 w/w%. In certain embodiments, the binder is present in an amount of about 3.0 w/w%. In certain embodiments, the binder is present in an amount of about 3.5 w/w%. In certain embodiments, the binder is present in an amount of about 4.0 w/w%. In certain embodiments, the binder is present in an amount of about 4.5 w/w%. In certain embodiments, the binder is present in an amount of about 5.0 w/w%. In certain embodiments, the binder is present in an amount of about 5.5 w/w%. In certain embodiments, the binder is present in an amount of about 6.0 w/w%. In certain embodiments, the binder is present in an amount of about 6.5 w/w%. In certain embodiments, the binder is present in an amount of about 7.0 w/w%. In certain embodiments, the binder is present in an amount of about 7.5 w/w%. In certain embodiments, the binder is present in an amount of about 8.0 w/w%. [0059] In certain embodiments, the binder is present in an amount of about 5.0±3.0 w/w%. In certain embodiments, the binder is present in an amount of about 5.0±2.8 w/w%. In certain embodiments, the binder is present in an amount of about 5.0±2.6 w/w%. In certain embodiments, the binder is present in an amount of about 5.0±2.4 w/w%. In certain embodiments, the binder is present in an amount of about 5.0±2.2 w/w%. In certain embodiments, the binder is present in an amount of about 5.0±2.0 w/w%. In certain embodiments, the binder is present in an amount of about 5.0±1.8 w/w%. In certain embodiments, the binder is present in an amount of about 5.0±1.6 w/w%. In certain embodiments, the binder is present in an amount of about 5.0±1.4 w/w%. In certain embodiments, the binder is present in an amount of about 5.0±1.2 w/w%. In certain embodiments, the binder is present in an amount of about 5.0±1.0 w/w%. In certain embodiments, the binder is present in an amount of about 5.0±0.8 w/w%. In certain embodiments, the binder is present in an amount of about 5.0±0.6 w/w%. In certain embodiments, the binder is present in an amount of about 5.0±0.4 w/w%. In certain embodiments, the binder is present in an amount of about 5.0±0.2 w/w% (e.g., 5.0 w/w%). [0060] In certain embodiments, the binder comprises crospovidone, and the crospovidone is present in an amount of about 5.0% w/w. Disintegrating Agent [0061] In certain embodiments, the formulation comprises a disintegrating agent. [0062] In certain embodiments, the disintegrating agent is selected from natural starch, a pregelatinized starch, a sodium starch, methylcrystalline cellulose, methylcellulose (e.g., Methocel®), croscarmellose, croscarmellose sodium, cross-linked sodium carboxymethy1 cellulose, cross-linked carboxymethyl cellulose, cross-linked croscarmellose, cross-linked starch such as sodium starch glycolate, cross-linked polymer such as crospovidone, cross- linked polyvinylpyrrolidone, sodium alginate, a clay, and a gum. Surfactant [0063] In certain embodiments, the formulation comprises a surfactant. [0064] In certain embodiments, the surfactant comprises sodium lauryl sulfate. [0065] In certain embodiments, the surfactant is present in an amount ranging from about 2.0 w/w% to about 8.0 w/w%. In certain embodiments, the surfactant is present in an amount ranging from about 2.0 w/w% to about 7.0 w/w%. In certain embodiments, the surfactant is present in an amount ranging from about 2.0 w/w% to about 6.0 w/w%. In certain embodiments, the surfactant is present in an amount ranging from about 2.0 w/w% to about 5.0 w/w%. In certain embodiments, the surfactant is present in an amount ranging from about 2.0 w/w% to about 4.0 w/w%. In certain embodiments, the surfactant is present in an amount ranging from about 2.0 w/w% to about 3.0 w/w%. In certain embodiments, the surfactant is present in an amount ranging from about 3.0 w/w% to about 8.0 w/w%. In certain embodiments, the surfactant is present in an amount ranging from about 3.0 w/w% to about 7.0 w/w%. In certain embodiments, the surfactant is present in an amount ranging from about 3.0 w/w% to about 6.0 w/w%. In certain embodiments, the surfactant is present in an amount ranging from about 3.0 w/w% to about 5.0 w/w%. In certain embodiments, the surfactant is present in an amount ranging from about 3.0 w/w% to about 4.0 w/w%. In certain embodiments, the surfactant is present in an amount ranging from about 4.0 w/w% to about 8.0 w/w%. In certain embodiments, the surfactant is present in an amount ranging from about 4.0 w/w% to about 7.0 w/w%. In certain embodiments, the surfactant is present in an amount ranging from about 4.0 w/w% to about 6.0 w/w%. In certain embodiments, the surfactant is present in an amount ranging from about 4.0 w/w% to about 5.0 w/w%. In certain embodiments, the surfactant is present in an amount ranging from about 5.0 w/w% to about 8.0 w/w%. In certain embodiments, the surfactant is present in an amount ranging from about 5.0 w/w% to about 7.0 w/w%. In certain embodiments, the surfactant is present in an amount ranging from about 5.0 w/w% to about 6.0 w/w%. In certain embodiments, the surfactant is present in an amount ranging from about 6.0 w/w% to about 8.0 w/w%. In certain embodiments, the surfactant is present in an amount ranging from about 6.0 w/w% to about 7.0 w/w%. [0066] In certain embodiments, the surfactant is present in an amount of about 2.0 w/w%. In certain embodiments, the surfactant is present in an amount of about 2.5 w/w%. In certain embodiments, the surfactant is present in an amount of about 3.0 w/w%. In certain embodiments, the surfactant is present in an amount of about 3.5 w/w%. In certain embodiments, the surfactant is present in an amount of about 4.0 w/w%. In certain embodiments, the surfactant is present in an amount of about 4.5 w/w%. In certain embodiments, the surfactant is present in an amount of about 5.0 w/w%. In certain embodiments, the surfactant is present in an amount of about 5.5 w/w%. In certain embodiments, the surfactant is present in an amount of about 6.0 w/w%. In certain embodiments, the surfactant is present in an amount of about 6.5 w/w%. In certain embodiments, the surfactant is present in an amount of about 7.0 w/w%. In certain embodiments, the surfactant is present in an amount of about 7.5 w/w%. In certain embodiments, the surfactant is present in an amount of about 8.0 w/w%. [0067] In certain embodiments, the surfactant is present in an amount of about 5.0±3.0 w/w%. In certain embodiments, the surfactant is present in an amount of about 5.0±2.8 w/w%. In certain embodiments, the surfactant is present in an amount of about 5.0±2.6 w/w%. In certain embodiments, the surfactant is present in an amount of about 5.0±2.4 w/w%. In certain embodiments, the surfactant is present in an amount of about 5.0±2.2 w/w%. In certain embodiments, the surfactant is present in an amount of about 5.0±2.0 w/w%. In certain embodiments, the surfactant is present in an amount of about 5.0±1.8 w/w%. In certain embodiments, the surfactant is present in an amount of about 5.0±1.6 w/w%. In certain embodiments, the surfactant is present in an amount of about 5.0±1.4 w/w%. In certain embodiments, the surfactant is present in an amount of about 5.0±1.2 w/w%. In certain embodiments, the surfactant is present in an amount of about 5.0±1.0 w/w%. In certain embodiments, the surfactant is present in an amount of about 5.0±0.8 w/w%. In certain embodiments, the surfactant is present in an amount of about 5.0±0.6 w/w%. In certain embodiments, the surfactant is present in an amount of about 5.0±0.4 w/w%. In certain embodiments, the surfactant is present in an amount of about 5.0±0.2 w/w% (e.g., 5.0 w/w%). [0068] In certain embodiments, the surfactant comprises sodium lauryl sulfate, and the surfactant is present in an amount of about 5.0% w/w. Lubricant [0069] In certain embodiments, the formulation comprises a lubricant. [0070] In certain embodiments, the lubricant comprises magnesium stearate. [0071] In certain embodiments, the lubricant is present in an amount ranging from about 0.1 w/w% to about 3.0 w/w%. In certain embodiments, the lubricant is present in an amount ranging from about 0.1 w/w% to about 2.5 w/w%. In certain embodiments, the lubricant is present in an amount ranging from about 0.1 w/w% to about 2.0 w/w%. In certain embodiments, the lubricant is present in an amount ranging from about 0.1 w/w% to about 1.5 w/w%. In certain embodiments, the lubricant is present in an amount ranging from about 0.1 w/w% to about 1.0 w/w%. In certain embodiments, the lubricant is present in an amount ranging from about 0.1 w/w% to about 0.5 w/w%. In certain embodiments, the lubricant is present in an amount ranging from about 0.5 w/w% to about 3.0 w/w%. In certain embodiments, the lubricant is present in an amount ranging from about 0.5 w/w% to about 2.5 w/w%. In certain embodiments, the lubricant is present in an amount ranging from about 0.5 w/w% to about 2.0 w/w%. In certain embodiments, the lubricant is present in an amount ranging from about 0.5 w/w% to about 1.5 w/w%. In certain embodiments, the lubricant is present in an amount ranging from about 0.5 w/w% to about 1.0 w/w%. In certain embodiments, the lubricant is present in an amount ranging from about 0.8 w/w% to about 3.0 w/w%. In certain embodiments, the lubricant is present in an amount ranging from about 0.8 w/w% to about 2.5 w/w%. In certain embodiments, the lubricant is present in an amount ranging from about 0.8 w/w% to about 2.0 w/w%. In certain embodiments, the lubricant is present in an amount ranging from about 0.8 w/w% to about 1.5 w/w%. In certain embodiments, the lubricant is present in an amount ranging from about 0.8 w/w% to about 1.0 w/w%. In certain embodiments, the lubricant is present in an amount ranging from about 1.2 w/w% to about 3.0 w/w%. In certain embodiments, the lubricant is present in an amount ranging from about 1.2 w/w% to about 2.5 w/w%. In certain embodiments, the lubricant is present in an amount ranging from about 1.2 w/w% to about 2.0 w/w%. In certain embodiments, the lubricant is present in an amount ranging from about 1.2 w/w% to about 1.5 w/w%. In certain embodiments, the lubricant is present in an amount ranging from about 1.5 w/w% to about 3.0 w/w%. In certain embodiments, the lubricant is present in an amount ranging from about 1.5 w/w% to about 2.5 w/w%. In certain embodiments, the lubricant is present in an amount ranging from about 1.5 w/w% to about 2.0 w/w%. [0072] In certain embodiments, the lubricant is present in an amount of about 0.1 w/w%. In certain embodiments, the lubricant is present in an amount of about 0.2 w/w%. In certain embodiments, the lubricant is present in an amount of about 0.3 w/w%. In certain embodiments, the lubricant is present in an amount of about 0.4 w/w%. In certain embodiments, the lubricant is present in an amount of about 0.5 w/w%. In certain embodiments, the lubricant is present in an amount of about 0.6 w/w%. In certain embodiments, the lubricant is present in an amount of about 0.7 w/w%. In certain embodiments, the lubricant is present in an amount of about 0.8 w/w%. In certain embodiments, the lubricant is present in an amount of about 0.9 w/w%. In certain embodiments, the lubricant is present in an amount of about 1.0 w/w%. In certain embodiments, the lubricant is present in an amount of about 1.1 w/w%. In certain embodiments, the lubricant is present in an amount of about 1.2 w/w%. In certain embodiments, the lubricant is present in an amount of about 1.3 w/w%. In certain embodiments, the lubricant is present in an amount of about 1.4 w/w%. In certain embodiments, the lubricant is present in an amount of about 1.5 w/w%. In certain embodiments, the lubricant is present in an amount of about 1.6 w/w%. In certain embodiments, the lubricant is present in an amount of about 1.8 w/w%. In certain embodiments, the lubricant is present in an amount of about 2.0 w/w%. In certain embodiments, the lubricant is present in an amount of about 2.2 w/w%. In certain embodiments, the lubricant is present in an amount of about 2.4 w/w%. In certain embodiments, the lubricant is present in an amount of about 2.6 w/w%. In certain embodiments, the lubricant is present in an amount of about 2.8 w/w%. In certain embodiments, the lubricant is present in an amount of about 3.0 w/w%. [0073] In certain embodiments, the surfactant is present in an amount of about 1.0±0.5 w/w%. In certain embodiments, the surfactant is present in an amount of about 1.0±0.4 w/w%. In certain embodiments, the surfactant is present in an amount of about 1.0±0.3 w/w%. In certain embodiments, the surfactant is present in an amount of about 1.0±0.2 w/w%. In certain embodiments, the surfactant is present in an amount of about 1.0±0.1 w/w% (e.g., 1.0 w/w%). [0074] In certain embodiments, the lubricant comprises magnesium stearate, and the lubricant is present in the particle formulation in an amount of about 1.0% w/w. [0075] In certain embodiments, the one or more pharmaceutically acceptable excipients comprises a diluent, a binder, a surfactant; and a lubricant. Exemplary Embodiments of the Formulations [0076] In certain embodiments, the formulation comprises a diluent, a binder, a surfactant, and a lubricant. [0077] In certain embodiments, the avatrombopag and the diluent are present in the formulation at a ratio of about 12:77. [0078] In certain embodiments, the diluent and the binder are present in the formulation at a ratio of about 77:5. [0079] In certain embodiments, the diluent and the surfactant are present in the formulation at a ratio of about 77:5. [0080] In certain embodiments, the diluent and the lubricant are present in the formulation at a ratio of about 77:1. [0081] In certain embodiments, the diluent, the binder, the surfactant, and the lubricant are present in the formulation at a ratio of about 12:77:5:5:1. [0082] In certain embodiments, the formulation comprises: about 11.8±3.0 w/w% of the avatrombopag monomaleate; about 77.2±20.0 w/w% of the diluent; about 5.0±3.0 w/w% of the binder; about 5.0±3.0 w/w% of the surfactant; and about 1.0±0.5 w/w% of the lubricant. [0083] In certain embodiments, the formulation comprises: about 11.8±3.0 mg of the avatrombopag monomaleate; about 49.2±10.0 mg of mannitol; about 28.0±10.0 mg of microcrystalline cellulose; about 5.0±3.0 mg of Crospovidone Type A; about 5.0±3.0 mg of sodium laurilsulfate; and about 1.0±0.5 mg of magnesium stearate. [0084] In certain embodiments, the formulation comprises: about 11.8 mg of the avatrombopag monomaleate; about 49.2 mg of mannitol; about 28.0 mg of microcrystalline cellulose; about 5.0 mg of Crospovidone Type A; about 5.0 mg of sodium laurilsulfate; and about 1.0 mg of magnesium stearate. Dosage Form [0085] In certain aspects, the present disclosure provides oral dosage forms, comprising the solid particle formulation disclosed herein. [0086] In certain embodiments, the oral dosage form is a capsule. [0087] In certain embodiments, the capsule is configured to be easily opened. Method of Use [0088] In certain aspects, the present disclosure provides methods of preparing a dispersed particle formulation, comprising dispersing the particle formulation disclosed herein in a media. [0089] In certain embodiments, the media is a solid media or a liquid media. [0090] In certain embodiments, the media is an aqueous media. [0091] In certain aspects, the present disclosure provides dispersed particle formulations, being prepared by the method disclosed herein. [0092] In certain aspects, the present disclosure provides methods of treating or preventing a disease in a subject, comprising administering to the subject the dispersed particle formulation disclosed herein. [0093] In certain aspects, the present disclosure provides uses of the dispersed particle formulation disclosed herein in the manufacture of a medicament for treating or preventing a disease in a subject. [0094] In certain aspects, the present disclosure provides the dispersed particle formulation disclosed herein for use in treating or preventing a disease in a subject. [0095] In certain aspects, the present disclosure provides methods of treating a disease in a subject, comprising administering to the subject the dispersed particle formulation disclosed herein. [0096] In certain aspects, the present disclosure provides uses of the dispersed particle formulation disclosed herein in the manufacture of a medicament for treating a disease in a subject. [0097] In certain aspects, the present disclosure provides the dispersed particle formulation disclosed herein for use in treating a disease in a subject. [0098] In certain embodiments, the disease or disorder is thrombocytopenia. [0099] In certain embodiments, thrombocytopenia is idiopathic thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), hemolytic-uremic syndrome (HUS), disseminated intravascular coagulation (DIC), paroxysmal nocturnal hemoglobinuria (PNH), antiphospholipid syndrome, systemic lupus erythematosus (SLE), post transfusion purpura, neonatal alloimmune thrombocytopenia (NAITP), splenic sequestration of platelets due to hypersplenism, dengue fever, thrombocytopenia of myelodysplastic syndromes (MDS), or chemotherapy-induced thrombocytopenia, severe aplastic anemia (SAA), post-hematopoietic stem cell transplant (HSCT), Evan’s syndrome, or genetic thrombocytopenias. [0100] In certain embodiments, the disease or disorder is immune thrombocytopenia (ITP). [0101] In certain embodiments, the patient is a pediatric patient. [0102] In certain embodiments, the patient is less than 18 years old. In certain embodiments, the patient is less than 5 years old. In certain embodiments, the patient is not able to swallow tablets or pills. [0103] In certain embodiments, the patient has had primary ITP for ≥6 months duration or has an insufficient response to previous treatment. [0104] In certain embodiments, the patient has an average of two platelet counts of < 30×10⁹ /L, with no single count of >35×10⁹ /L. Definitions [0105] As used in the specification and appended claims, unless specified to the contrary, the following terms have the meaning indicated below. [0106] The term "about" when used before a numerical value indicates that the value may vary within a reasonable range, such as within ±10%, ±5%, ±3%, or ±1 % of the stated value. [0107] A “subject” to which administration is contemplated includes, but is not limited to, humans (i.e., a male or female of any age group, e.g., a pediatric subject (e.g, infant, child, adolescent) or an adult subject (e.g., young adult, middle aged adult or senior adult) and/or a non-human animal, e.g., a mammal such as primates (e.g., cynomolgus monkeys, rhesus monkeys), cattle, pigs, horses, sheep, goats, rodents, cats, and/or dogs. In certain embodiments, the subject is a human. In certain embodiments, the subject is a patient. In certain embodiments, the subject is a non-human animal. [0108] An “effective amount” means the amount of a compound that, when administered to a subject for treating or preventing a disease, is sufficient to affect such treatment or prevention. The “effective amount” can vary depending on the compound, the disease and its severity, and the age, weight, etc., of the subject to be treated. A “therapeutically effective amount” refers to the effective amount for therapeutic treatment. A “prophylatically effective amount” refers to the effective amount for prophylactic treatment. [0109] “Preventing”, “prevention” or “prophylactic treatment” refers to a reduction in risk of acquiring or developing a disease or disorder (i.e., causing at least one of the clinical symptoms of the disease not to develop in a subject not yet exposed to a disease-causing agent, or in a subject who is predisposed to the disease in advance of disease onset). [0110] The term “prophylaxis” is related to “prevention,” and refers to a measure or procedure, the purpose of which is to prevent, rather than to treat or cure a disease. Non limiting examples of prophylactic measures may include the administration of vaccines; the administration of low molecular weight heparin to hospital patients at risk for thrombosis due, for example, to immobilization, and the administration of an anti-malarial agent such as chloroquine, in advance of a visit to a geographical region where malaria is endemic or the risk of contracting malaria is high. [0111] “Treating” or “treatment” or “therapeutic treatment” of any disease or disorder refers, in one embodiment, to ameliorating the disease or disorder (i.e., arresting the disease or reducing the manifestation, extent or severity of at least one of the clinical symptoms thereof). In another embodiment, “treating” or “treatment” refers to ameliorating at least one physical parameter, which may not be discernible by the subject. In yet another embodiment, “treating” or “treatment” refers to modulating the disease or disorder, either physically, (e.g., stabilization of a discernible symptom), physiologically, (e.g., stabilization of a physical parameter), or both. In a further embodiment, “treating” or “treatment” relates to slowing the progression of the disease. [0112] As used herein, the term “subject in need thereof” refers to a subject having a disease or disorder disclosed herein, or having an increased risk of developing the disease or disorder disclosed herein. A subject in need thereof can be one who has been previously diagnosed or identified as having a disease or disorder disclosed herein. A subject in need thereof can also be one who is suffering from a disease or disorder disclosed herein. Alternatively, a subject in need thereof can be one who has an increased risk of developing such disease or disorder relative to the population at large (i.e., a subject who is predisposed to developing such disease or disorder relative to the population at large). A subject in need thereof can have a refractory or resistant a disease or disorder disclosed herein (i.e., a disease or disorder disclosed herein that does not respond or has not yet responded to treatment). The subject may be resistant at start of treatment or may become resistant during treatment. In some embodiments, the subject in need thereof received and failed all known effective therapies for a disease or disorder disclosed herein. In some embodiments, the subject in need thereof received at least one prior therapy. [0113] As used herein, the term “treating” or “treat” describes the management and care of a patient for the purpose of combating a disease or disorder and includes the administration of a compound of the present disclosure, or a pharmaceutically acceptable salt, polymorph or solvate thereof, to alleviate the symptoms or complications of the disease or disorder, or to eliminate the disease or disorder. The term “treat” can also include treatment of a cell in vitro or an animal model. It is to be appreciated that references to “treating” or “treatment” include the alleviation of established symptoms of a condition. “Treating” or “treatment” of a state, disorder or condition therefore includes: (1) preventing or delaying the appearance of clinical symptoms of the state, disorder or condition developing in a human that may be afflicted with or predisposed to the state, disorder or condition but does not yet experience or display clinical or subclinical symptoms of the state, disorder or condition, (2) inhibiting the state, disorder or condition, i.e., arresting, reducing or delaying the development of the disease or a relapse thereof (in case of maintenance treatment) or at least one clinical or subclinical symptom thereof, or (3) relieving or attenuating the disease, i.e., causing regression of the state, disorder or condition or at least one of its clinical or subclinical symptoms. [0114] As used herein, the term “pharmaceutical composition” is a formulation containing the compounds of the present disclosure in a form suitable for administration to a subject. In one embodiment, the pharmaceutical composition is in bulk or in unit dosage form. The unit dosage form is any of a variety of forms, including, for example, a capsule, an IV bag, a tablet, a single pump on an aerosol inhaler or a vial. In one embodiment, the active compound is mixed under sterile conditions with a pharmaceutically acceptable carrier, and with any preservatives, buffers, or propellants that are required. [0115] As used herein, the term “pharmaceutically acceptable” refers to those compounds, anions, cations, materials, compositions, carriers, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio. [0116] As used herein, the term “pharmaceutically acceptable excipient” means an excipient that is useful in preparing a pharmaceutical composition that is generally safe, non-toxic and neither biologically nor otherwise undesirable, and includes excipient that is acceptable for veterinary use as well as human pharmaceutical use. A “pharmaceutically acceptable excipient” as used in the specification and claims includes both one and more than one such excipient. [0117] The pharmaceutical compositions containing active compounds of the present disclosure may be manufactured in a manner that is generally known, e.g., by means of conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping, or lyophilising processes. Pharmaceutical compositions may be formulated in a conventional manner using one or more pharmaceutically acceptable carriers comprising excipients and/or auxiliaries that facilitate processing of the active compounds into preparations that can be used pharmaceutically. [0118] “Pharmaceutically acceptable salt” refers to a salt of a compound of the disclosure that is pharmaceutically acceptable and that possesses the desired pharmacological activity of the parent compound. In particular, such salts are non-toxic may be inorganic or organic acid addition salts and base addition salts. [0119] In the salt form, it is understood that the ratio of the compound to the cation or anion of the salt can be 1:1, or any ratio other than 1:1, e.g., 3:1, 2:1, 1:2, or 1:3. [0120] As use herein, the phrase “compound of the disclosure” refers to those compounds which are disclosed herein, both generically and specifically. [0121] It will be understood that the compound disclosed herein and any pharmaceutically acceptable salts thereof, comprise stereoisomers, mixtures of stereoisomers, polymorphs of all isomeric forms of said compound. [0122] It will be understood that while the compound disclosed herein may be presented in one particular configuration, such particular configuration is not to be construed as limiting the disclosure to one or another isomer, tautomer, regioisomer or stereoisomer, nor does it exclude mixtures of isomers, tautomers, regioisomers or stereoisomers. In some embodiments, the presentation of a compound herein in a particular configuration intends to encompass, and to refer to, each of the available isomers, tautomers, regioisomers, and stereoisomers of the compound, or any mixture thereof; while the presentation further intends to refer to the specific configuration of the compound. [0123] As used herein, the term “isomerism” means compounds that have identical molecular formulae but differ in the sequence of bonding of their atoms or in the arrangement of their atoms in space. Isomers that differ in the arrangement of their atoms in space are termed “stereoisomers.” Stereoisomers that are not mirror images of one another are termed “diastereoisomers,” and stereoisomers that are non-superimposable mirror images of each other are termed “enantiomers” or sometimes optical isomers. A mixture containing equal amounts of individual enantiomeric forms of opposite chirality is termed a “racemic mixture.” [0124] As used herein, the term “geometric isomer” means the diastereomers that owe their existence to hindered rotation about double bonds or a cycloalkyl linker (e.g., 1,3-cyclobutyl). These configurations are differentiated in their names by the prefixes cis and trans, or Z and E, which indicate that the groups are on the same or opposite side of the double bond in the molecule according to the Cahn-Ingold-Prelog rules. [0125] It is to be understood that the compounds of the present disclosure may be depicted as different chiral isomers or geometric isomers. It is also to be understood that when compounds have chiral isomeric or geometric isomeric forms, all isomeric forms are intended to be included in the scope of the present disclosure, and the naming of the compounds does not exclude any isomeric forms, it being understood that not all isomers may have the same level of activity. [0126] It is to be understood that the structures and other compounds discussed in this disclosure include all atropic isomers thereof. It is also to be understood that not all atropic isomers may have the same level of activity. [0127] As used herein, the term “atropic isomers” are a type of stereoisomer in which the atoms of two isomers are arranged differently in space. Atropic isomers owe their existence to a restricted rotation caused by hindrance of rotation of large groups about a central bond. Such atropic isomers typically exist as a mixture, however as a result of recent advances in chromatography techniques, it has been possible to separate mixtures of two atropic isomers in select cases. [0128] As used herein, the term “tautomer” is one of two or more structural isomers that exist in equilibrium and is readily converted from one isomeric form to another. This conversion results in the formal migration of a hydrogen atom accompanied by a switch of adjacent conjugated double bonds. Tautomers exist as a mixture of a tautomeric set in solution. In solutions where tautomerisation is possible, a chemical equilibrium of the tautomers will be reached. The exact ratio of the tautomers depends on several factors, including temperature, solvent and pH. The concept of tautomers that are interconvertible by tautomerisations is called tautomerism. Of the various types of tautomerism that are possible, two are commonly observed. In keto-enol tautomerism a simultaneous shift of electrons and a hydrogen atom occurs. Ring-chain tautomerism arises as a result of the aldehyde group (-CHO) in a sugar chain molecule reacting with one of the hydroxy groups (-OH) in the same molecule to give it a cyclic (ring-shaped) form as exhibited by glucose. [0129] It is to be understood that the compounds of the present disclosure may be depicted as different tautomers. It should also be understood that when compounds have tautomeric forms, all tautomeric forms are intended to be included in the scope of the present disclosure, and the naming of the compounds does not exclude any tautomer form. It will be understood that certain tautomers may have a higher level of activity than others. [0130] Compounds that have the same molecular formula but differ in the nature or sequence of bonding of their atoms or the arrangement of their atoms in space are termed “isomers”. Isomers that differ in the arrangement of their atoms in space are termed “stereoisomers”. Stereoisomers that are not mirror images of one another are termed “diastereomers” and those that are non-superimposable mirror images of each other are termed “enantiomers”. When a compound has an asymmetric center, for example, it is bonded to four different groups, a pair of enantiomers is possible. An enantiomer can be characterized by the absolute configuration of its asymmetric center and is described by the R- and S-sequencing rules of Cahn and Prelog, or by the manner in which the molecule rotates the plane of polarised light and designated as dextrorotatory or levorotatory (i.e., as (+) or (-)-isomers respectively). A chiral compound can exist as either individual enantiomer or as a mixture thereof. A mixture containing equal proportions of the enantiomers is called a “racemic mixture”. [0131] The compounds of this disclosure may possess one or more asymmetric centers; such compounds can therefore be produced as individual (R)- or (S)-stereoisomers or as mixtures thereof. Unless indicated otherwise, the description or naming of a particular compound in the specification and claims is intended to include both individual enantiomers and mixtures, racemic or otherwise, thereof. The methods for the determination of stereochemistry and the separation of stereoisomers are well-known in the art (see discussion in Chapter 4 of “Advanced Organic Chemistry”, 4th edition J. March, John Wiley and Sons, New York, 2001), for example by synthesis from optically active starting materials or by resolution of a racemic form. Some of the compounds of the disclosure may have geometric isomeric centers (E- and Z- isomers). It is to be understood that the present disclosure encompasses all optical, diastereoisomers and geometric isomers and mixtures thereof that possess inflammasome inhibitory activity. [0132] The present disclosure also encompasses compounds of the disclosure as defined herein which comprise one or more isotopic substitutions. EXAMPLARY EMBODIMENTS EXAMPLARY EMBODIMENT 1. A solid particle formulation, comprising: avatrombopag, having the structure of

, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients. EXAMPLARY EMBODIMENT 2. The solid particle formulation of any one of the preceding exemplary embodiments, wherein the pharmaceutically acceptable salt of avatrombopag is avatrombopag monomaleate. EXAMPLARY EMBODIMENT 3. The solid particle formulation of any one of the preceding exemplary embodiments, wherein the solid particle is a granule. EXAMPLARY EMBODIMENT 4. The solid particle formulation of any one of the preceding exemplary embodiments, wherein the population of solid particles has an average particle diameter of about 400 µm to about 600 µm. EXAMPLARY EMBODIMENT 5. The solid particle formulation of any one of the preceding exemplary embodiments, wherein the population of solid particles has bulk density of about 0.58 g/mL to about 0.66 g/mL. EXAMPLARY EMBODIMENT 6. The solid particle formulation of any one of the preceding exemplary embodiments, wherein the avatrombopag or the pharmaceutically acceptable salt thereof is present in an amount ranging from about 5.0% w/w to about 18.0% w/w. EXAMPLARY EMBODIMENT 7. The solid particle formulation of any one of the preceding exemplary embodiments, wherein the avatrombopag is present in an amount of about 10.0±5% w/w, or the pharmaceutically acceptable salt of avatrombopag is present in an amount of about 11.8±5% w/w. EXAMPLARY EMBODIMENT 8. The solid particle formulation of any one of the preceding exemplary embodiments, wherein one or more pharmaceutically acceptable excipients comprise a diluent, a binder, a surfactant, or a lubricant. EXAMPLARY EMBODIMENT 9. The solid particle formulation of any one of the preceding exemplary embodiments, wherein the diluent is selected from lactose, sucrose (e.g., Dipac®), dextrose, dextrates, maltodextrin, mannitol, xylitol (e.g., Xylitab®), sorbitol, cyclodextrins, calcium phosphate, calcium sulfate, starches, modified starches, cellulose, microcrystalline cellulose (e.g., Avicel®), microcellulose, and talc. EXAMPLARY EMBODIMENT 10. The solid particle formulation of any one of the preceding exemplary embodiments, wherein the diluent is present in an amount ranging from about 70.0 w/w% to about 85.0 w/w%. EXAMPLARY EMBODIMENT 11. The solid particle formulation of any one of the preceding exemplary embodiments, wherein the diluent comprises microcrystalline cellulose and mannitol. EXAMPLARY EMBODIMENT 12. The solid particle formulation of any one of the preceding exemplary embodiments, wherein the diluent comprises microcrystalline cellulose and mannitol, wherein the microcrystalline cellulose is present in an amount of about 30.0±5.0% w/w, and the mannitol is present in an amount of about 49.0±5.0% w/w. EXAMPLARY EMBODIMENT 13. The solid particle formulation of any one of the preceding exemplary embodiments, wherein the binder is selected from polyvinylpyrrolidone (PVP) (e.g., PVP Kl 5, PVP K19, PVP K25, PVP K30, Povidone® CL, Kollidon® CL, Polyplasdone® XL-10, and Povidone® K-12), cross-linked polyvinyl N-pyrrolidone (crospovidone), hydroxy propyl cellulose (HPC), hydroxy propyl methyl cellulose (HPMC), microcrystalline cellulose (MCC), sodium carboxy methyl cellulose, methylcellulose, lactose, sucrose, sorbitol, xylitol, mannitol, starch, sodium alginate, gelatin, and polyethylene glycol (PEG). EXAMPLARY EMBODIMENT 14. The solid particle formulation of any one of the preceding exemplary embodiments, wherein the binder is present in an amount of from about 2.0 w/w% to about 8.0 w/w%. EXAMPLARY EMBODIMENT 15. The solid particle formulation of any one of the preceding exemplary embodiments, wherein the binder comprises crospovidone, and the crospovidone is present in an amount of about 5.0 w/w%. EXAMPLARY EMBODIMENT 16. The solid particle formulation of any one of the preceding exemplary embodiments, wherein the surfactant comprises sodium lauryl sulfate. EXAMPLARY EMBODIMENT 17. The solid particle formulation of claim 16, wherein the surfactant is present in an amount of from about 2.0 w/w% to about 8.0 w/w%. EXAMPLARY EMBODIMENT 18. The solid particle formulation of any one of the preceding exemplary embodiments, wherein the surfactant comprises sodium lauryl sulfate, and the sodium lauryl sulfate is present in an amount of about 5.0 w/w%. EXAMPLARY EMBODIMENT 19. The solid particle formulation of any one of the preceding exemplary embodiments, wherein the lubricant comprises magnesium stearate. EXAMPLARY EMBODIMENT 20. The solid particle formulation of any one of the preceding exemplary embodiments, wherein the lubricant is present in an amount of from about 0.1 w/w% to about 3.0 w/w%. EXAMPLARY EMBODIMENT 21. The solid particle formulation of any one of the preceding exemplary embodiments, wherein the lubricant comprises magnesium stearate, and the magnesium stearate is present in the particle formulation in an amount of about 1.0 w/w%. EXAMPLARY EMBODIMENT 22. The solid particle formulation of any one of the preceding exemplary embodiments, comprising: about 11.8±3.0 w/w% of the avatrombopag monomaleate; about 77.0±20.0 w/w% of the diluent; about 5.0±3.0 w/w% of the binder; about 5.0±3.0 w/w% of the surfactant; and about 1.0±0.9 w/w% of the lubricant. EXAMPLARY EMBODIMENT 23. The solid particle formulation of any one of the preceding exemplary embodiments, comprising: about 11.8±3.0 mg of the avatrombopag monomaleate; about 49.2±10.0 mg of mannitol; about 28.0±10.0 mg of microcrystalline cellulose; about 5.0±3.0 mg of Crospovidone Type A; about 5.0±3.0 mg of sodium laurilsulfate; and about 1.0±0.9 mg of magnesium stearate. EXAMPLARY EMBODIMENT 24. The solid particle formulation of any one of the preceding exemplary embodiments, comprising: about 11.8 mg of the avatrombopag monomaleate; about 49.2 mg of mannitol; about 28.0 mg of microcrystalline cellulose; about 5.0 mg of Crospovidone Type A; about 5.0 mg of sodium laurilsulfate; and about 1.0 mg of magnesium stearate. EXAMPLARY EMBODIMENT 25. The solid particle formulation of any one of the preceding exemplary embodiments, wherein the formulation is substantially free from lactose. EXAMPLARY EMBODIMENT 26. An oral dosage form, comprising the solid particle formulation of any one of the preceding exemplary embodiments. EXAMPLARY EMBODIMENT 27. The oral dosage form of any one of the preceding exemplary embodiments, wherein the oral dosage form is a capsule. EXAMPLARY EMBODIMENT 28. The oral dosage form of any one of the preceding exemplary embodiments, wherein the capsule is configured to be easily opened. EXAMPLARY EMBODIMENT 29. A method of preparing a dispersed particle formulation, comprising dispersing the particle formulation of any one of the preceding exemplary embodiments in a media. EXAMPLARY EMBODIMENT 30. The method of any one of the preceding exemplary embodiments, wherein the media is a solid media or a liquid media. EXAMPLARY EMBODIMENT 31. The method of any one of the preceding exemplary embodiments, wherein the media is an aqueous media. EXAMPLARY EMBODIMENT 32. A dispersed particle formulation, being prepared by the method of any one of the preceding exemplary embodiments. EXAMPLARY EMBODIMENT 33. A method of treating or preventing a disease in a subject, comprising administering to the subject the dispersed particle formulation of any one of the preceding exemplary embodiments. EXAMPLARY EMBODIMENT 34. Use of the dispersed particle formulation of any one of the preceding exemplary embodiments in the manufacture of a medicament for treating or preventing a disease in a subject. EXAMPLARY EMBODIMENT 35. The dispersed particle formulation of any one of the preceding exemplary embodiments for use in treating or preventing a disease in a subject. EXAMPLARY EMBODIMENT 36. The method, use, or particle formulation for use of any one of the preceding exemplary embodiments, wherein the disease or disorder is idiopathic thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), hemolytic- uremic syndrome (HUS), disseminated intravascular coagulation (DIC), paroxysmal nocturnal hemoglobinuria (PNH), antiphospholipid syndrome, systemic lupus erythematosus (SLE), post transfusion purpura, neonatal alloimmune thrombocytopenia (NAITP), splenic sequestration of platelets due to hypersplenism, dengue fever, thrombocytopenia of myelodysplastic syndromes (MDS), or chemotherapy-induced thrombocytopenia). EXAMPLARY EMBODIMENT 37. The method, use, or particle formulation for use of any one of the preceding exemplary embodiments, wherein the disease or disorder is immune thrombocytopenia (ITP). EXAMPLES [0133] In order that the invention described herein may be more fully understood, the following examples are set forth. The examples described in this application are offered to illustrate the formulations and methods provided herein and are not to be construed in any way as limiting their scope. Example 1. Exemplary Capsule Formulations [0134] Capsules of Avatrombopag Powder for Oral Suspension, 10 mg, consist of white/light blue capsules containing white to off-white granules were prepared. Details of the appearance and physical dimensions of the capsules are shown in Table E1. Table E1.

[0135] The qualitative and quantitative compositions of Capsules of Avatrombopag Powder for Oral Suspension, 10 mg are listed in Table E2. Table E2.

NF = National Formulary(U.S.), Ph. Eur. = European Pharmacopoeia, USP = United States Pharmacopeia ^a A_{vatrombopag maleate, 11.787 mg is equivalent to 10.0 mg avatrombopag free base} Example 2. Development of Exemplary Formulations [0136] The exemplary formulation was developed to allow for administration of avatrombopag to patients who cannot or will not swallow tablets. [0137] This drug product consists of granules of drug product contained in a two-piece hard gelatin capsule that is specifically designed to be easily opened by patients and which enables users to dose the contents of a capsule in a consistent manner. This capsule offers a more convenient and simple way to sprinkle drugs on food or in beverages as compared to standard capsules that require sufficient dexterity to open the capsule locking mechanism. Components [0138] A dry granulation process was developed for the formulation using conventional excipients suitable for dry granulation. The excipients for Capsules of Avatrombopag Powder for Oral Suspension, 10 mg, were selected to optimize dissolution of the drug product and are shown in Table E3. Table E3.

[0139] The components of Capsules of Avatrombopag Powder for Oral Suspension, 10 mg, for the proposed clinical studies and intended commercial manufacturing scale are described below. Drug Substance [0140] Avatrombopag maleate was used. Excipients [0141] The compatibility of the drug substance, avatrombopag maleate, with potential excipients was assessed focusing on the stability of the formulation. Binary mixtures of API and the excipients in a ratio of API/excipient (1:10) were prepared and exposed to elevated temperature and humidity conditions for a period of 4 weeks. The samples were analyzed for evidence of avatrombopag degradation. After 4 weeks, no drug substance degradation was observed in mixtures with any excipients used in the formulation for Capsules of Avatrombopag Powder for Oral Suspension, 10 mg. In addition, the stability study for the capsules confirms that avatrombopag maleate is compatible with all the excipients used in the formulation. [0142] All of the excipients used are the subject of monographs in the European Pharmacopoeia (PhEur) and the United States Pharmacopeia (USP). In addition, all the excipients used appear in the United States Food and Drug Administration Inactive Ingredients Database (IID) and the proposed excipient levels will not exceed the maximum potency per unit dose listed in the database for FDA approved drug products. Further, none of the excipients, at the levels proposed, are known to be of special concern for use in formulations. All of the proposed excipients are TSE/BSE free; they are synthetic and do not contain any raw materials derived from animal origin. Capsules of Avatrombopag Powder for Oral Suspension, 10 mg [0143] Avatrombopag Powder for Suspension in a Capsule, 10 mg, was developed. The original capsule for this formulation was difficult to open and, therefore, the formulation was transferred to a sprinkle capsule to ease opening of the dosage unit. [0144] The batch formulas for Capsules of Avatrombopag Powder for Suspension, 10 mg, is provided in Table . Table E4.

^a 1 mg avatrombopag maleate = 0.85 mg avatrombopag ^b 11.788 mg avatrombopag maleate = 10.0 mg avatrombopag [0145] For administration, it is intended that the top portion of the capsule is removed, and the capsule contents are suspended in an appropriate vehicle by the caregiver immediately prior to administration. Therefore, a sprinkle capsule was identified as an appropriate capsule shell. [0146] A sprinkle capsule consists of a two-piece, hard, hypromellose capsule that is specifically designed to be easily opened by patients and which enables users to dose the contents of a capsule in a consistent manner. This capsule would offer a more convenient and simple way to sprinkle drugs on food or in beverages as compared to standard capsules that require sufficient dexterity and strength to reopen the strong capsule locking mechanism. The two-piece Vcaps® Plus hypromellose capsules sourced from Capsugel® are manufactured from non-animal sourced materials and have an innovative closure that needs less force to open so it can be opened much easier and safer. Dissolution Development for Capsules of Avatrombopag Powder for Oral Suspension, 10 mg [0147] The development of dissolution conditions for Capsules of Avatrombopag Powder for Suspension, 10 mg, began by initially assessing the suitability of the dissolution parameters successfully developed for avatrombopag film-coated tablets. The dissolution method parameters developed for the avatrombopag film-coated tablets were not appropriate for the granules due to differences in the physical nature of the capsule granules versus the tablets. Due to the suspension granules immediately settling to the bottom of the vessel in a cone formation at sample introduction, which impeded complete dissolution, the dissolution vessels were upgraded to peak dissolution vessels that contain a “dimple” at the bottom of the vessel to minimize coning of the drug product. In addition, due to the greater surface area of the granules versus the tablets, the paddle speed and surfactant concentration were adjusted to provide a more discriminatory dissolution profile for the granules. [0148] The dissolution profile for Capsules of Avatrombopag Powder for Suspension, 10 mg is provided in Error! Reference source not found.1. Food Compatibility Study [0149] An in vitro food and vehicle compatibility study to assess the integrity, potency, stability, and homogeneity of avatrombopag with various liquids and foods at different consistencies was completed to identify compatible vehicles for administration. [0150] Prior to the food compatibility study, a basic screening was performed according to FDA Guidance “Use of Liquids and/or Soft Foods as Vehicles for Drug Administration: General Considerations for Selection and In Vitro Methods for Product Quality Assessments”, that demonstrated that avatrombopag drug substance is stable in Fed State Simulated Gastric Fluid (FeSSGF). The drug substance was exposed to FeSSGF for 10 minutes and 1 hour. No significant degradation was observed in the sample preparation at initial conditions (control), the 10-minute preparation, or the 1 hour preparation (99.7% and 100.2% of the control, respectively), indicating the drug substance is stable in FeSSGF. [0151] For the food compatibility study, Capsules of Avatrombopag Powder for Oral Suspension, 10 mg, were opened and the granules were transferred to a media bottle. For each food/liquid vehicle, the contents of the capsules were combined with the food vehicles in the proportion of 3 capsules per 5 mL of vehicle. The study evaluated the suitability of the drug product at the time of administration after being exposed to apple sauce, strawberry jelly, Pedialyte^®, and orange juice. Following exposure to the food substance, potency, stability, homogeneity, and dissolution were performed on the drug product/food substance mixture along with a drug product control sample. In addition, an abbreviated food study was performed using bottled water which evaluated the suitability of the drug product at the time of administration after being exposed to the bottled water for 30 minutes. Following exposure to the bottled water for 30 minutes, potency, and stability assessments were completed, and the results were compared to a drug product control sample. [0152] The results indicated that apple sauce, Pedialyte^®, orange juice, strawberry jelly, and water are safe and effective vehicles for delivering avatrombopag drug product to patients. Container Closure [0153] Capsules of Avatrombopag Powder for Suspension, 10 mg, are packaged in 60cc white HDPE bottles with an induction sealed child resistant polypropylene cap. Microbiological Attributes [0154] All excipients used for the manufacturing of Capsules of Avatrombopag Powder for Suspension, 10 mg, are of pharmacopeia quality. In accordance with good manufacturing practice requirements and to ensure a high level of quality control, the finished product specification includes microbiological testing appropriate for an oral formulation using the compendial methods listed below: [0155] USP<61>/ Ph. Eur. 2.6.12. / JP 4.05 Microbiological Examination of Non-sterile Products: Microbial Enumeration Tests. [0156] USP<62>/ Ph. Eur. 2.6.13. / JP 4.05 Microbiological Examination of Non-sterile Products: Tests for Specified Microorganisms. [0157] The limits of microbial enumeration tests are as follows: ^ Total aerobic microbial count: Not more than 10³ CFU/g ^ Total combined yeasts/molds count: Not more than 10² CFU/g The limits of test for specified microorganisms are as follows. ^ Absence of Escherichia coli ^ Absence of Pseudomonas aeruginosa ^ Absence of Staphylococcus aureus Example 3. Manufacture of Exemplary Formulations Batch Formula [0158] The manufacturing formula for batches of Capsules of Avatrombopag Powder for Oral Suspension, 10 mg, at the intended commercial scale (120,000 capsules) is provided in Table . Table E5. Batch Formula for Capsules of Avatrombopag Powder for Oral Suspension, 10 mg

^a Avatrombopag maleate, 11.787 mg = avatrombopag free form, 10 mg Description of Manufacturing Process and Process Controls [0159] The manufacturing process for Capsules of Avatrombopag Powder for Oral Suspension, 10 mg, consist of sieving, blending, lubrication, roller compaction, capsule filling, bulk packaging, and then primary packaging into HDPE bottles. A flow diagram of the manufacturing process of Capsules of Avatrombopag Powder for Oral Suspension, 10 mg, is provided in Error! Reference source not found.3. [0160] The manufacturing process for Capsules of Avatrombopag Powder for Oral Suspension, 10 mg, is outlined below. 1. Blend mannitol in the slant cone blender to coat the blender. Charge Avatrombopag API, Kollidon-CL Crospovidone and Kollidon SLS to the blender and blend. 2. Discharge the mixture from the blender and pass through the Comil. Pass the Microcrystalline Cellulose through the Comil and combine with other materials. 3. Charge the milled materials to the slant cone blender and blend. 4. Sieve the magnesium stearate through a hand screen. Charge the deagglomerated magnesium stearate to a 1 liter amber glass bottle, then fill the bottle approximately ½ full with the blend from step 3. Mix at moderate speed. Sieve the Turbula-mixed material through a screen and charge to the slant cone blender. 5. The blend is discharged and stored in sealed container double lined with polyethylene bags, with a desiccant between the liners, and a desiccant between the outside liner and drum until roller compaction. 6. Perform roller compaction. Make adjustments as necessary to generate ribbons with the target thickness density. 7. Pass the roller compacted ribbons through the Comil. Sieve cut the milled ribbons on a #50 mesh sieve. Collect the milled granules retained on the #50 mesh screen as acceptable granules. Collect the milled granules that pass through the #50 mesh screen for additional roller compaction. 8. Repeat steps 6 – 7 a total of 4 passes, collecting the milled granules retained on the #50 mesh screen as acceptable granules. Charge all acceptable retained granules to the slant cone blender and blend. 9. The blended granulation is placed in containers and encapsulated on an automatic encapsulator. During encapsulation, the granule fill weight is 100 mg ± 5 mg. In-process weight checks are performed. 10. The weight-sorted filled capsules are collected in a plastic drum with lid, double-lined with polyethylene bags, with one desiccant between the polyethylene bags and one desiccant between the polyethylene bag and the drum. 11. The bulk capsules are packaged into HDPE bottles with child-resistant caps. Controls of Critical Steps and Intermediates [0161] The critical process steps, tests and current acceptance criteria for in-process controls for Capsules of Avatrombopag Powder for Oral Suspension, 10 mg, are under development. The current proposed in-process tests are shown in Table and Table . Table E6.

Table E7.

[0162] The granulation process is identified as a critical manufacturing step for Capsules of Avatrombopag Powder for Oral Suspension, 10 mg. Control of critical manufacturing steps is accomplished through established operating parameters critical to the drug product meeting its final product specifications. The critical process step is described in Table , with the respective parameter settings and acceptance ranges. Table E8.

CPP = Critical process parameter ^a second pass is for granules that passed through the #50 mesh screen (manufacturing process step #7) [0163] Ribbon thickness, roll pressure, roll speed, and auger speed may all be related to the dissolution, which is a Critical Quality Attribute (CQA) for Capsules of Avatrombopag Powder for Oral Suspension, 10 mg.

EQUIVALENTS [0164] The details of one or more embodiments of the disclosure are set forth in the accompanying description above. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, the preferred methods and materials are now described. Other features, objects, and advantages of the disclosure will be apparent from the description and from the claims. In the specification and the appended claims, the singular forms include plural referents unless the context clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. All patents and publications cited in this specification are incorporated by reference. [0165] The foregoing description has been presented only for the purposes of illustration and is not intended to limit the disclosure to the precise form disclosed, but by the claims appended hereto.

Claims

CLAIMS WHAT IS CLAIMED IS: 1. A solid particle formulation, comprising: avatrombopag, having the structure of

, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.

2. The solid particle formulation of claim 1, wherein the pharmaceutically acceptable salt of avatrombopag is avatrombopag monomaleate.

3. The solid particle formulation of claim 1 or 2, wherein the solid particle is a granule.

4. The solid particle formulation of any one of claims 1-3, wherein the population of solid particles has an average particle diameter of about 400 µm to about 600 µm.

5. The solid particle formulation of any one of claims 1-4, wherein the population of solid particles has bulk density of about 0.58 g/mL to about 0.66 g/mL.

6. The solid particle formulation of any one of claims 1-5, wherein the avatrombopag or the pharmaceutically acceptable salt thereof is present in an amount ranging from about 5.0% w/w to about 18.0% w/w.

7. The solid particle formulation of any one of claims 1-5, wherein the avatrombopag is present in an amount of about 10.0±5% w/w, or the pharmaceutically acceptable salt of avatrombopag is present in an amount of about 11.8±5% w/w.

8. The solid particle formulation of any one of claims 1-7, wherein one or more pharmaceutically acceptable excipients comprise a diluent, a binder, a surfactant, or a lubricant.

9. The solid particle formulation of claim 8, wherein the diluent is selected from lactose, sucrose (e.g., Dipac®), dextrose, dextrates, maltodextrin, mannitol, xylitol (e.g., Xylitab®), sorbitol, cyclodextrins, calcium phosphate, calcium sulfate, starches, modified starches, cellulose, microcrystalline cellulose (e.g., Avicel®), microcellulose, and talc.

10. The solid particle formulation of claim 9, wherein the diluent is present in an amount ranging from about 70.0 w/w% to about 85.0 w/w%.

11. The solid particle formulation of claim 9 or 10, wherein the diluent comprises microcrystalline cellulose and mannitol.

12. The solid particle formulation of claim 11, wherein the diluent comprises microcrystalline cellulose and mannitol, wherein the microcrystalline cellulose is present in an amount of about 30.0±5.0% w/w, and the mannitol is present in an amount of about 49.0±5.0% w/w.

13. The solid particle formulation of claim 8, wherein the binder is selected from polyvinylpyrrolidone (PVP) (e.g., PVP Kl 5, PVP K19, PVP K25, PVP K30, Povidone® CL, Kollidon® CL, Polyplasdone® XL-10, and Povidone® K-12), cross-linked polyvinyl N- pyrrolidone (crospovidone), hydroxy propyl cellulose (HPC), hydroxy propyl methyl cellulose (HPMC), microcrystalline cellulose (MCC), sodium carboxy methyl cellulose, methylcellulose, lactose, sucrose, sorbitol, xylitol, mannitol, starch, sodium alginate, gelatin, and polyethylene glycol (PEG).

14. The solid particle formulation of claim 13, wherein the binder is present in an amount of from about 2.0 w/w% to about 8.0 w/w%.

15. The solid particle formulation of claim 13 or 14, wherein the binder comprises crospovidone, and the crospovidone is present in an amount of about 5.0 w/w%.

16. The solid particle formulation of claim 8, wherein the surfactant comprises sodium lauryl sulfate.

17. The solid particle formulation of claim 16, wherein the surfactant is present in an amount of from about 2.0 w/w% to about 8.0 w/w%.

18. The solid particle formulation of claim 17, wherein the surfactant comprises sodium lauryl sulfate, and the sodium lauryl sulfate is present in an amount of about 5.0 w/w%.

19. The solid particle formulation of claim 8, wherein the lubricant comprises magnesium stearate.

20. The solid particle formulation of claim 19, wherein the lubricant is present in an amount of from about 0.1 w/w% to about 3.0 w/w%.

21. The solid particle formulation of claim 20, wherein the lubricant comprises magnesium stearate, and the magnesium stearate is present in the particle formulation in an amount of about 1.0 w/w%.

22. The solid particle formulation of claim 8, comprising: about 11.8±3.0 w/w% of the avatrombopag monomaleate; about 77.0±20.0 w/w% of the diluent; about 5.0±3.0 w/w% of the binder; about 5.0±3.0 w/w% of the surfactant; and about 1.0±0.9 w/w% of the lubricant.

23. The solid particle formulation of claim 8, comprising: about 11.8±3.0 mg of the avatrombopag monomaleate; about 49.2±10.0 mg of mannitol; about 28.0±10.0 mg of microcrystalline cellulose; about 5.0±3.0 mg of Crospovidone Type A; about 5.0±3.0 mg of sodium laurilsulfate; and about 1.0±0.9 mg of magnesium stearate.

24. The solid particle formulation of claim 8, comprising: about 11.8 mg of the avatrombopag monomaleate; about 49.2 mg of mannitol; about 28.0 mg of microcrystalline cellulose; about 5.0 mg of Crospovidone Type A; about 5.0 mg of sodium laurilsulfate; and about 1.0 mg of magnesium stearate.

25. The solid particle formulation of any one of claims 1-24, wherein the formulation is substantially free from lactose.

26. An oral dosage form, comprising the solid particle formulation of any one of claims 1- 25.

27. The oral dosage form of claim 26, wherein the oral dosage form is a capsule.

28. The oral dosage form of claim 26, wherein the capsule is configured to be easily opened.

29. A method of preparing a dispersed particle formulation, comprising dispersing the particle formulation of any one of claims 1-28 in a media.

30. The method of claim 29, wherein the media is a solid media or a liquid media.

31. The method of claim 29, wherein the media is an aqueous media.

32. A dispersed particle formulation, being prepared by the method of any one of claims 29-31.

33. A method of treating or preventing a disease in a subject, comprising administering to the subject the dispersed particle formulation of claim 32.

34. Use of the dispersed particle formulation of claim 32 in the manufacture of a medicament for treating or preventing a disease in a subject.

35. The dispersed particle formulation of claim 32 for use in treating or preventing a disease in a subject.

36. The method, use, or particle formulation for use of any one of claims 33-35, wherein the disease or disorder is idiopathic thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), hemolytic-uremic syndrome (HUS), disseminated intravascular coagulation (DIC), paroxysmal nocturnal hemoglobinuria (PNH), antiphospholipid syndrome, systemic lupus erythematosus (SLE), post transfusion purpura, neonatal alloimmune thrombocytopenia (NAITP), splenic sequestration of platelets due to hypersplenism, dengue fever, thrombocytopenia of myelodysplastic syndromes (MDS), or chemotherapy-induced thrombocytopenia).

37. The method, use, or particle formulation for use of claim 36, wherein the disease or disorder is immune thrombocytopenia (ITP).