[go: up one dir, main page]

WO2025153584A1 - Forme galénique solide auto-émulsifiante - Google Patents

Forme galénique solide auto-émulsifiante

Info

Publication number
WO2025153584A1
WO2025153584A1 PCT/EP2025/050971 EP2025050971W WO2025153584A1 WO 2025153584 A1 WO2025153584 A1 WO 2025153584A1 EP 2025050971 W EP2025050971 W EP 2025050971W WO 2025153584 A1 WO2025153584 A1 WO 2025153584A1
Authority
WO
WIPO (PCT)
Prior art keywords
dosage form
self
emulsifying
crosslinked poly
loaded
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/EP2025/050971
Other languages
English (en)
Inventor
Andrea HAERTEL
Thorsten Cech
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
BASF SE
Original Assignee
BASF SE
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by BASF SE filed Critical BASF SE
Publication of WO2025153584A1 publication Critical patent/WO2025153584A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/167—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface
    • A61K9/1676—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface having a drug-free core with discrete complete coating layer containing drug

Definitions

  • the present invention relates to a solid self-emulsifying dosage form comprising a self-emulsifying drug delivery system (SEDDS) which is loaded onto crosslinked poly(vinyl pyrrolidone).
  • SEDDS self-emulsifying drug delivery system
  • beneficial ingredients e.g., in the administration of a pharmaceutically active ingredient, to ensure adequate absorption of the active ingredient in the gastrointestinal tract and plasma levels high enough to be therapeutically active.
  • This is a non-trivial task, especially in cases where the beneficial ingredient has a low solubility in water. It is commonly recognized in the pharmaceutical industry that on average more than 40% of newly discovered drug candidates are poorly water-soluble.
  • the lipophilic beneficial ingredient may be incorporated into a lipid-based self-emulsifying composition. It is desirable to convert the liquid lipid-based systems into powders which reveal good stability and can be easily processed and transformed into convenient dosage forms like capsules or tablets. To this end, it has been suggested to adsorb the self-emulsifying composition on solid carriers, e.g., solid inorganic carriers.
  • Such lipid-based self-emulsifying composition are known in the state of the art.
  • US 2017/119674 Al describes a composition comprising a lipophilic compound having a log P of at least 5, and a self-emulsifying vehicle.
  • the selfemulsifying vehicle comprises (a) a fat component and (b) a hydrophilic surfactant.
  • the self-emulsifying vehicle is adsorbed into a solid core comprising silicon dioxide.
  • US 5,449,521 discloses amorphous drug absorbed onto a support material.
  • the support material may be crosslinked polymers, linear polymers, water-soluble complexing agents, and porous inorganic materials.
  • the drug and support material are co-ground in a mill with its grinding chamber saturated with the vapor of one or more solvents able to solubilize the drug.
  • solid self-emulsifying dosage form of the invention which comprises a self-emulsifying composition which is loaded onto crosslinked poly (vi nyl pyrrolidone).
  • crosslinked poly (vi nyl pyrrolidone)” may suitably be abbreviated as “crosslinked PVP”, or "cPVP”.
  • the invention further relates to a method for preparing a solid self-emulsifying dosage form, the method comprising
  • the crosslinked poly(vinyl pyrrolidone) is generally in the form a finely-divided solid, i.e., a powder.
  • the crosslinked poly (vi nyl pyrrolidone) has a particle size distribution (PSD), wherein at least 90% of the particles have a particle size of more than 100 pm, and at least 70% of the particles have a particle size of more than 50 pm.
  • PSD is suitably determined using an air jet sieve after 5 min at 20 mbar.
  • the self-emulsifying composition comprises a beneficial ingredient, and a self-emulsifying vehicle.
  • beneficial ingredient is meant an ingredient that exerts a beneficial effect, e.g., a therapeutically beneficial effect, when administered to a subject, e.g., to a human or other mammals.
  • beneficial ingredient refers to any compound, mixture of compounds, or composition of matter consisting of a compound, which produces a beneficial or useful result. Any suitable beneficial ingredient can be used.
  • Exemplary pharmaceutically active ingredients include, e.g., mirtazapine, olanzapine, ondansetron, NSAIDs, acetaminophen, enalapril, famotidine, fluoxetine, lorazepam, loperamide, loratidine, narcotic analgesics, e.g., morphine, hydrocodone, and the like, oxazepam, piroxicam, rizatriptan, zolmitriptan, zolpidem, hyoscyamine and salts thereof, e.g., hyoscyamine sulfate, and the like.
  • mirtazapine e.g., olanzapine, ondansetron, NSAIDs, acetaminophen, enalapril, famotidine, fluoxetine, lorazepam, loperamide, loratidine, narcotic
  • the present invention allows for enhancing intestinal absorption of poorly water- soluble beneficial ingredients.
  • the invention may specifically be applicable to beneficial ingredients conforming to Class lib or IV, according to the Developability Classification System, DCS.
  • the lipid may be selected from mono-glycerides, di-glycerides, tri-glycerides of C 14 -C 24 fatty acids, or mixtures thereof.
  • the fatty acid may be saturated, monounsaturated or polyunsaturated fatty acids or derivatives thereof.
  • Each chain in the fatty acid or glyceride may have, for example, 0, 1, 2, or 3 double bonds.
  • the lipid comprises a mono-glyceride and a tri-glyceride, wherein the weight ratio of tri-glycerides to mono-glycerides is in the range from 1:2 to 6:1.
  • the lipid is selected from soybean oil, corn oil, glycerol monooleate, glyceryl mono-caprylocaprate, winterized oil composed of long-chain mono-, di-, and tri-glycerides, medium chain tri-glyceride based lipids, and mixtures thereof.
  • the surfactant may be selected from a hydrophilic surfactant with a hydrophilic- lipophilic balance (HLB) value of 13 or higher.
  • HLB hydrophilic- lipophilic balance
  • the HLB system assigns numerical values to surface-active substances; the HLB values of lipophilic substances are low, and those of hydrophilic ones are higher (Fiedler, H. B., Lexikon der Hilfsstoffe fur Pharmazie, Kosmetik, and angrenzende füre, 4th edition, Aulendorf: ECV-Editio-Cantor-Verlag (1996)).
  • Suitable surfactants are selected from:
  • esters of mono- or di-glycerides such as the acetic, succinic, lactic, citric or tartaric esters
  • polyoxyethylene sorbitan fatty acid derivatives such as polysorbates, e.g., polysorbate 80
  • anionic surfactants such as sodium lauryl sulfate or sodium oleate
  • the self-emulsifying composition is emulsified with a suitable amount of water.
  • the weight ratio of the self-emulsifying composition and water may be in the range of from 3:1 to 1:2.
  • the self-emulsifying composition may be mixed with water and stirred. After contacting the resulting emulsion with the crosslinked poly(vinyl pyrrolidone), the emulsion is adsorbed onto the external and internal surface(s) of the crosslinked poly(vinyl pyrrolidone). As a result, a wet powder of loaded crosslinked poly(vinyl pyrrolidone) is obtained.
  • said wet powder is subsequently dried to obtain a dried powder.
  • water originating from the step of emulsifying as described above, and, if present, additional co-solvents originating from the self-emulsifying composition may be removed from the wet powder in the drying step.
  • Fluidized bed dryers are used for reducing the moisture content of a powder.
  • the wet powder is fluidized, for example in a metal tube, and hot supply air is introduced at high pressures through a perforated bed plate.
  • the wet powder is lifted from the bed plate and suspended in a stream of air (fluidized state).
  • Heat transfer is accomplished by direct contact between the wet powder and the hot supply air.
  • the vaporized liquid i.e., water and, if present, ethanol, is carried away by exhaust gases exiting the metal tube via the opening at the opposite side to the bed plate.
  • the resulting self-emulsifying vehicles 1 to 3 were mixed with menthol as beneficial ingredient and water to obtain emulsions 1 to 9 as shown in table 4. Mixing was carried out using an overhead stirrer or magnetic stirrer.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dispersion Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Medicinal Preparation (AREA)

Abstract

Une forme galénique solide auto-émulsifiante comprend une composition auto-émulsifiante chargée sur de la poly(vinylpyrrolidone) réticulée. La composition liquide auto-émulsifiante est convertie en une poudre qui présente une bonne stabilité et peut être facilement traitée et transformée en formes galéniques pratiques telles que des capsules ou des comprimés. La forme galénique solide auto-émulsifiante présente des propriétés adéquates de libération de substances.
PCT/EP2025/050971 2024-01-17 2025-01-16 Forme galénique solide auto-émulsifiante Pending WO2025153584A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP24152334.9 2024-01-17
EP24152334 2024-01-17

Publications (1)

Publication Number Publication Date
WO2025153584A1 true WO2025153584A1 (fr) 2025-07-24

Family

ID=89620538

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2025/050971 Pending WO2025153584A1 (fr) 2024-01-17 2025-01-16 Forme galénique solide auto-émulsifiante

Country Status (1)

Country Link
WO (1) WO2025153584A1 (fr)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5449521A (en) 1988-11-28 1995-09-12 Vectorpharma N.A. Inc. Supported drugs with increased dissolution rate, and a process for their preparation
US20020119198A1 (en) * 2000-07-24 2002-08-29 Ping Gao Self-emulsifying drug delivery systems for extremely water-insoluble, lipophilic drugs
US20030133984A1 (en) * 2000-04-10 2003-07-17 Ambuehl Michael Pharmaceutical compositions
US20170119674A1 (en) 2014-06-19 2017-05-04 Solural Pharma ApS Solid oral dosage form of lipophilic compounds
US20210236628A1 (en) * 2020-02-05 2021-08-05 Jubilant Generics Limited Self-emulsifying solid oral dosage forms of allergen and their preparation thereof
CN113456588B (zh) * 2021-07-05 2023-01-03 沈阳药科大学 一种醋酸阿比特龙固体自微乳及其制备方法

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5449521A (en) 1988-11-28 1995-09-12 Vectorpharma N.A. Inc. Supported drugs with increased dissolution rate, and a process for their preparation
US20030133984A1 (en) * 2000-04-10 2003-07-17 Ambuehl Michael Pharmaceutical compositions
US20020119198A1 (en) * 2000-07-24 2002-08-29 Ping Gao Self-emulsifying drug delivery systems for extremely water-insoluble, lipophilic drugs
US20170119674A1 (en) 2014-06-19 2017-05-04 Solural Pharma ApS Solid oral dosage form of lipophilic compounds
US20210236628A1 (en) * 2020-02-05 2021-08-05 Jubilant Generics Limited Self-emulsifying solid oral dosage forms of allergen and their preparation thereof
CN113456588B (zh) * 2021-07-05 2023-01-03 沈阳药科大学 一种醋酸阿比特龙固体自微乳及其制备方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DHRITLAHRE RAKESH KUMAR ET AL: "Self-emulsifying formulations to augment therapeutic efficacy of nutraceuticals: From concepts to clinic", TRENDS IN FOOD SCIENCE & TECHNOLOGY, ELSEVIER SCIENCE PUBLISHERS, GB, vol. 115, 28 June 2021 (2021-06-28), pages 347 - 365, XP086701573, ISSN: 0924-2244, [retrieved on 20210628], DOI: 10.1016/J.TIFS.2021.06.046 *

Similar Documents

Publication Publication Date Title
US20100143481A1 (en) Method of preparing solid dosage forms of multi-phasic pharmaceutical compositions
US20090060993A1 (en) Solid pharmaceutical composition for enhanced delivery of coenzyme q-10 and ubiquinones
EP1104290B1 (fr) Microemulsions comme formes pharmaceutiques solides destinees a une administration orale
US6793934B1 (en) Solid oral dosage form
US20100143420A1 (en) Multi-phasic pharmaceutical formulations of poorly water-soluble drugs for reduced fed/fasted variability and improved oral bioavailability
US20030072798A1 (en) Solid self-emulsifying dosage form for improved delivery of poorly soluble hydrophobic compounds and the process for preparation thereof
CN100579514C (zh) 通过受控制的凝聚而制备颗粒物的方法以及提高生物利用度的方法
US5891845A (en) Drug delivery systems utilizing liquid crystal structures
DK170110B1 (da) Farmaceutisk præparat med langsom frigivelse og anvendelse af fumarsyre til fremstilling af præpar atet
DE69727153T2 (de) Im magen verweilende orale arzneistoffdosisformen zur gesteuerten freisetzung schwerlöslicher arzneistoffe und unlöslicher stoffe
EP1771157B1 (fr) Forme galenique multiparticulaire pour principes actifs faiblement solubles, et procede de production de la forme galenique
DE68915695T2 (de) Zubereitungen mit kontrollierter Wirkstoffabgabe.
JP2002522473A5 (fr)
US20050037073A1 (en) Solid self-emulsifying dosage form for improved delivery of poorly soluble hydrophobic compounds and the process for preparation thereof
CN1726909A (zh) 丁苯酞自乳化释药体系及其制备方法和应用
AU4679999A (en) Micro-osmotic controlled drug delivery systems
KR20070119700A (ko) 페노피브레이트 및 계면 활성제 혼합물을 함유하는 제제
JP2005533774A (ja) ジバルプロエクスソジウムの放出遅延剤
WO2025153584A1 (fr) Forme galénique solide auto-émulsifiante
US20230277464A1 (en) Tablet dosage forms for lipid-based drug delivery systems
CN101239048A (zh) 环孢素a速释固体剂型及其制备方法
WO2024142045A1 (fr) Formulations orales à libération contrôlée de médicaments lipophiles

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 25700211

Country of ref document: EP

Kind code of ref document: A1