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WO2009151574A1 - Film extrudé à chaud par coulée contenant du dioxyde de silicium - Google Patents

Film extrudé à chaud par coulée contenant du dioxyde de silicium Download PDF

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Publication number
WO2009151574A1
WO2009151574A1 PCT/US2009/003455 US2009003455W WO2009151574A1 WO 2009151574 A1 WO2009151574 A1 WO 2009151574A1 US 2009003455 W US2009003455 W US 2009003455W WO 2009151574 A1 WO2009151574 A1 WO 2009151574A1
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WO
WIPO (PCT)
Prior art keywords
weight
hot melt
extruded composition
composition
present
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.)
Ceased
Application number
PCT/US2009/003455
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English (en)
Inventor
Feng ZENG
Lee Eleuterius
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.)
AUXILIUM PHARMACEUTICALS
Original Assignee
AUXILIUM PHARMACEUTICALS
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 AUXILIUM PHARMACEUTICALS filed Critical AUXILIUM PHARMACEUTICALS
Publication of WO2009151574A1 publication Critical patent/WO2009151574A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays

Definitions

  • the present invention relates generally to a single or multilayered laminated hot melt extruded film that may be applied to a mucosal surface to deliver a therapeutic agent. More specifically, the hot melt extruded film is based on silicon dioxide, polyethylene oxide, at least one additional polymer, at least one additive, and according to some embodiments, at least one therapeutic agent.
  • Oral dosage forms are designed to enable sufficient availability of the therapeutic agent at its site of action.
  • the bioavailability of a drug depends on several parameters, such as on the physiochemical nature of the active compound, the dosage form, as well as on physiological factors.
  • Many substances obtained from modern drug discovery are problematic because of insufficient bioavailability.
  • Such molecules often exhibit very low aqueous solubility and limited solubility in oils.
  • Nucleoside derivatives for instance, are often potent antiviral (e.g., HIV, HCV, Herpes simplex, CMV) and anticancer chemotherapeutic agents but their utility is often limited by poor pharmacokinetic properties that limit the absorption of the nucleoside from the gut and the intracellular concentration of the nucleoside derivatives.
  • the production of drug forms, particularly thin films, by HME is accompanied by persistent problems of buildup of the molten extrudate on the die head openings and adhesion to the calendering equipment during the extrusion process.
  • the hot melt-processable polymers and ingredients are blended in an extruder. Through heat, shear, and pressure, the dry powders are fused to form a homogenous, molten material.
  • the extruder feeds the molten material in a continuous process to the top of the calendering section in between the first and second heated calender rolls. The rolls rotate in opposite directions to help spread the extrudate across the width of the rolls.
  • the extrudate winds between the first and second, second and third, third and fourth rolls, etc. After passing through the calender section, the material moves through another series of rolls where it is stretched and gradually cooled forming a film or sheet then wound into master rolls.
  • HPC hydroxypropyl cellulose
  • HPMC hydroxypropylmethyl cellulose
  • an HME film composition with a reduced tendency to build up on die head opening and adhere during the calendering is a desirable goal.
  • the present invention is directed to compositions and processes that permit extended operation run times without shutting down the extrusion line for clean-up due to extrudate adhesion and buildup.
  • a hot melt extrusion (HME) composition includes silicon dioxide, polyethylene oxide, at least one additional polymer, and at least one additive.
  • an HME composition further includes at least one therapeutic agent.
  • a method of processing a mixture into a thin film includes the steps of: forming a mixture comprising silicon dioxide, polyethylene oxide, at least one additional polymer, and at least one additive; extruding said extrudate to the top of a calendering section; and winding the extrudate into master rolls of thin film.
  • a method of processing a hot melt extruded composition into a thin film further includes blending at least one therapeutic agent into a molten extrudate.
  • a method of drug delivery includes applying to a mucosal surface an HME composition, wherein the extrusion composition includes silicon dioxide, polyethylene oxide, at least one additional polymer, at least one additive, and at least one therapeutic agent.
  • ranges are used as shorthand for describing each and every value that is within the range. Any value within the range can be selected as the terminus of the range.
  • a hot melt extrusion (HME) composition includes: (A) at least one detackifier, (B) at least one polymer, and (C) at least one additive.
  • an HME composition further includes: (D) at least one therapeutic agent.
  • a method of processing an HME composition includes combining: (A) at least one detackifier, (B) at least one polymer, and (C) at least one additive.
  • a method of processing an HME composition further includes combining: (D) at least one therapeutic agent with (A), (B), and (C).
  • a method of drug delivery includes applying to a mucosal surface an HME composition, wherein the extrusion composition includes at least one detackifier, at least one polymer, at least one additive, and at least one therapeutic agent.
  • detackifiers may be used in the preparation of an HME composition as known to those who are skilled in the art.
  • Suitable detackifiers for use in the present invention should perform at least three primary functions.
  • the detackifier should physically reduce intermolecular and intramolecular association of the polymer resin thereby reducing the adhesion of the molten extrudate to the extrusion/calendering equipment.
  • the second primary function of the detackifier is to allow the extruded film to be wound into a roll and placed in a container without the film either adhering to itself or its container.
  • the detackifier should also act as a glidant, thereby improving the feeding of the powdered/granulated polymers into the extrusion/calendering equipment.
  • the detackif ⁇ er may be any inorganic or organic species capable of physically restricting the intermolecular or intramolecular association of the polymer resin in the dry or molten state.
  • Particulate matter such as diatamaceous earth and ground silica having a median particle size of about 6 to about 10 microns are examples of suitable detackifiers useful in the present invention. In one embodiment, the median particle size of a suitable detackif ⁇ er is about 7 microns.
  • silicon dioxide is used as a detackif ⁇ er. It has been found, surprisingly, that the addition of even small amounts of silicon dioxide prevents adhesion of a composition of the invention to the processing equipment.
  • silicon dioxide suitable for use in some embodiments of the present invention includes SIPERNAT® 160PQ produced by Degussa AG.
  • the HME composition includes silicon dioxide in an amount of about 0.1% to about 30%, more preferably about 1% to about 20%, and most preferably about 1.50% to about 10% by weight.
  • polymer as used herein shall include any thermoplastic matrix polymers suitable for use in the present invention. Polymer choice can be a critical factor to obtain the desired drug-release profile during formulation development for an HME composition. Suitable polymers for use in the present invention must facilitate processing in the extruder, generate an acceptable melt viscosity, torque, barrel pressure, drive-motor amperage for processing, and must not result in the degradation of any raw materials. Under a given set of processing conditions, higher viscosity materials generally result in higher values of torque, pressure, and drive-motor amperage. This is significant as all extrusion/calendering equipment have maximum values of these attributes that may not be exceeded without causing damage and degradation to both the equipment and the chemical components of an HME composition.
  • suitable polymers must not only facilitate processing in the extruder, but must also exhibit the desired drug-release profile.
  • an HME composition includes at least one polymer. In some embodiments, an HME composition includes two or more polymers in combination. In some embodiments, an HME composition includes three or more polymers in combination. In some embodiments, an HME composition includes at least one polymer in an amount of about 60% to about 99%, more preferably about 75% to about 98%, and most preferably about 90% to about 97% by weight. In some embodiments, an HME composition includes two or more polymers in a combined amount of about 60% to about 99%, more preferably about 75% to about 98%, and most preferably about 90% to about 97% by weight. In some embodiments, an HME composition includes three or more polymers in a combined amount of about 60% to about 99%, more preferably about 75% to about 98%, and most preferably about 90% to about 97% by weight.
  • Polymers that may be used in accordance with some embodiments of the present invention include, by way of example and without limitation, various hot melt-processable cellulose derivatives, hydroxypropyl cellulose (HPC), polyethylene oxide (PEO), acrylic acid polymers, hydroxyethyl cellulose, homopolymers and copolymers of these polymers and their pharmaceutically acceptable salts, and combinations thereof.
  • HPC hydroxypropyl cellulose
  • PEO polyethylene oxide
  • acrylic acid polymers hydroxyethyl cellulose
  • homopolymers and copolymers of these polymers and their pharmaceutically acceptable salts, and combinations thereof include, by way of example and without limitation, various hot melt-processable cellulose derivatives, hydroxypropyl cellulose (HPC), polyethylene oxide (PEO), acrylic acid polymers, hydroxyethyl cellulose, homopolymers and copolymers of these polymers and their pharmaceutically acceptable salts, and combinations thereof.
  • the following polymers may be used: polyacrylates, poly(meth)acrylates, copolymers of acryl and methacryl derivatives, and vinyl compounds (e.g., using the following monomers: acrylic acid, methacrylic acid, acrylic acid ethyl ester, acrylic acid butyl ester, acrylic acid octyl ester, 2-esthylhexylacrylate, 2-hydroxyethyl acrylate and vinyl acetate).
  • polysiloxanes preferably self-adhesive polysiloxanes; silicone rubbers; hydocarbon polymers, preferably polyisobutylene, polyisoprene, styrene-isoprene-styrene block copolymers and styrene butadiene-styrene block copolymers; pressure sensitive adhesive preparations based on cellulose derivatives (e.g., ethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose) and adhesive resins (e.g., colophony and colophony derivatives) may be used in some embodiments.
  • cellulose derivatives e.g., ethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose
  • adhesive resins e.g., colophony and colophony derivatives
  • suitable polymers for use in the present invention include low viscosity, water-soluble, thermoplastic polyethylene oxide (PEO).
  • PEO thermoplastic polyethylene oxide
  • Polyethylene oxide is a white, free-flowing, hydrophilic, crystalline polymer powder available in 100,000- 7,000,000 Da molecular weights.
  • PEO is suitable for use in the present invention due in part to its broad processing window. Using PEO in HME formulations also allows for a dry, continuous, efficient process; reduces processing steps; and no compressibility requirements [0034] C.
  • Suitable additives for use in the present invention include any compound that may by way of example and without limitation: improve the film composition, drug stability and solubility, control drug release, enhance bioadhesion, reduce or increase matrix erosion time, modify extrusion characteristics or physical properties of the extrudate and film, and does not otherwise interfere with the efficacy or results in the degradation of the other components of an HME composition.
  • Suitable additives for use in the present invention include but are not limited to: pH modifying or buffering agents to improve drug stability and solubility; cross- linking agents to reduce matrix erosion time, control drug release, or enhance bioadhesion; antioxidants to inhibit oxidation and deterioration of preparations by oxidation; release rate modifiers; chelating agents; thickening agents (e.g., alginates, pectin); stabilizers (e.g., polyethoxylated sorbitan fatty acid esters such as TWEEN® or polyethoxylated fatty alcohols such as BRIJ®); surfactants; preservatives to prevent the growth of microorganisms (e.g., sorbic acid and its salts); paraben; fiavorants, sweeteners (e.g., aspartame, saccharine), colorants (e.g., quinoline yellow or TiO 2 ), and/or fragrance to impart a pleasant flavor, color, and/or odor to a extrudated
  • an HME composition includes at least one additive.
  • an HME composition includes a pH modifying or buffering agent.
  • an HME composition includes citric acid.
  • an HME composition includes a pH modifying or buffering agent in an amount of about 0.01% to about 5%, more preferably 0.1% to about 2.5%, and most preferably 0.5% to about 1% by weight.
  • an HME composition includes an antioxidant.
  • the antioxidant is butylated hydroxytoluene.
  • an HME composition includes an antioxidant in an amount of about 0.01% to about 2%, more preferably 0.05% to about 1%, most preferably about 0.1% to about 0.5% by weight.
  • an HME film includes and delivers a therapeutically effective amount of a therapeutic agent. Any molecular weight drug and its equivalent forms
  • Suitable therapeutic agents for use in the present invention may be any drug or compound that can be administered through the skin or a mucosal surface and does not decompose under the conditions of melt extrusion.
  • mucosal surface means any moist anatomical membrane or surface on a mammal including but not limited to oral, buccal, vaginal, nasal, rectal, or ophthalmic surfaces.
  • the amount of the therapeutic agent component in the complete preparation can vary within wide limits depending on the activity and release rate. For most drugs, their passage through the skin or mucosa will be the rate-limiting step in delivery. Thus, the amount of drug and the rate of release are typically selected so as to provide delivery characterized by a pseudo-zero order time dependency for a prolonged period of time.
  • the minimum amount of drug in the system is selected based on the amount of drug which passes through the skin or mucosa in the time span for which the device is to provide a therapeutically effective amount.
  • the content of therapeutic agent in the present invention can be in the range from about 0% to about 45%, more preferably from about 2.5% to about 25%, and most preferably from about 5% to about 10%, of the total weight of the preparation. The only conditions are that the preparation is still HME-processable and the therapeutic agent may be administered through the skin or mucosal surface.
  • Preferred therapeutic agents are hydrophilic, not relatively volatile or reactive with the other extrusion components, and may be incorporated into an HME composition.
  • the therapeutic agent is a component integral to the molten extrudate.
  • therapeutic agents not stable under the temperature and shearing conditions of an HME process may be applied to the extruded films using techniques that are known to those skilled in the art. By way of example and without limitation, these therapeutic agents can be dissolved in a solvent and coated onto the extruded films.
  • Suitable therapeutic agents for use in the present invention by way of example and without limitation include: analgesics, androgens, anesthethics, anoretics, anti-acne agents, antibiotics, anticholinergics, anti-diabetic agents, anti-fungals, antihistamines, antiinflammatory agents, anti-malarials, anti-migraine agents, anti-Parkinson's and/or anti- Alzhiemers's agents, anti-psychotics and/or anti-anxiety agents, antiseptics, anti-ulcerative agents, anti-virals, anxiolytic agents, ⁇ - and ⁇ -adrenergic agonists, central nervous system stimulants and agents, chemotherapeutic agents, cholinergics, enzymes, estrogens, hormones, muscle relaxants, minerals, narcotic antagonist agents, peptides, progestational agents,
  • Suitable therapeutic agents for use in the present invention may be any drug or compound that can be administered through the skin or a mucosal surface and does not decompose under the conditions of melt extrusion.
  • mucosal surface means any moist anatomical membrane or surface on a mammal including but not limited to oral, buccal, vaginal, nasal, rectal, or ophthalmic surfaces.
  • the amount of the therapeutic agent component in the complete preparation can vary within wide limits depending on the activity and release rate. For most drugs, their passage through the skin or mucosa will be the rate-limiting step in delivery. Thus, the amount of drug and the rate of release are typically selected so as to provide delivery characterized by a pseudo-zero order time dependency for a prolonged period of time.
  • the minimum amount of drug in the system is selected based on the amount of drug which passes through the skin or mucosa in the time span for which the device is to provide a therapeutically effective amount.
  • the content of therapeutic agent in the present invention can be in the range from about 0% to about 45%, more preferably from about 2.5% to about 25%, and most preferably from about 5% to about 10%, of the total weight of the preparation. The only conditions are that the preparation is still HME-processable and the therapeutic agent may be administered through the skin or mucosal surface.
  • Preferred therapeutic agents are hydrophilic, not relatively volatile or reactive with the other extrusion components, and may be incorporated into an HME composition.
  • the therapeutic agent is a component integral to the molten extrudate.
  • therapeutic agents not stable under the temperature and shearing conditions of an HME process may be applied to the extruded films using techniques that are known to those skilled in the art. By way of example and without limitation, these therapeutic agents can be dissolved in a solvent and coated onto the extruded films.
  • Suitable therapeutic agents for use in the present invention by way of example and without limitation include: analgesics, androgens, anesthethics, anoretics, anti-acne agents, antibiotics, anticholinergics, anti-diabetic agents, anti-fungals, antihistamines, anti- inflammatory agents, anti-malarials, anti-migraine agents, anti-Parkinson's and/or anti- Alzhiemers's agents, anti-psychotics and/or anti-anxiety agents, antiseptics, anti-ulcerative agents, anti-virals, anxiolytic agents, ⁇ - and ⁇ -adrenergic agonists, central nervous system stimulants and agents, chemotherapeutic agents, cholinergics, enzymes, estrogens, hormones, muscle relaxants, minerals, narcotic antagonist agents, peptides, progestational agents, proteins, and others known to those of ordinary skill in the medical arts, and combinations thereof.
  • the therapeutic agent is an opioid analgesic.
  • the opioid analgesic is fentanyl citrate.
  • the fentanyl citrate is present in an amount of about 0.01% to about 25%, more preferably from about 0.5% to about 10%, and most preferably from about 1% to about 5% by weight.
  • Processing conditions, equipment design, polymer selection, and the various uses of additives in the formulation are some of the factors that effect an HME composition.
  • the components are processed in a conventional way in extruders, preferably in single or twin screw extruders at a temperature in the range of about 50°C to about 200 0 C.
  • Shaping the extrudate into the solid compositions according to the present invention can take place, for example, by calendering the extrudate and converting it into thin films.
  • the polymer resin is blended with specific ingredients such as stabilizers to prevent thermal degradation; modifiers for clarity, heat stability or opacity characteristics; pigments; lubricants and processing aids; anti-static agents; UV inhibitors; and flame retardants.
  • the mixed ingredients are blended in a kneader or extruder. Through heat, shear and pressure, the dry powders are fused to form a homogenous, molten material.
  • the extruder feeds the molten material in a continuous process to the top of the calendering section of the calendering line in between first and second heated calender rolls. Typically, four rolls are used to form three nips or gaps.
  • the rolls are configured in an "L" shape or an inverted “L” shape or they may be in other configurations. The rolls vary in size to accommodate different film widths. The rolls have separate temperature and speed controls.
  • the material proceeds through the nip between the first two rolls, referred to as the feed nip.
  • the rolls rotate in opposite directions to help spread the material across the width of the rolls.
  • the material winds between the first and second, second and third, third and fourth rolls, etc.
  • the gap between rolls decreases in thickness between each of the rolls so that the material is thinned between the sets of rolls as it proceeds.
  • After passing through the calender section the material moves through another series of rolls where it is stretched and gradually cooled forming a film or sheet. The cooled material is then wound into master rolls.
  • a method of processing an HME composition into a thin film includes the continuous process steps of: (a) blending at least one detackifier (e.g., silicon dioxide), at least one hot melt processable polymer, polyethylene oxide, and at least one hot melt processable additive into a molten extrudate; (b) extruding said extrudate to the top of the calendering section; and (c) winding the extrudate into master rolls of thin film.
  • a method of processing an HME composition into a thin film further comprises blending at least one therapeutic agent into the molten extrudate.
  • the present invention relates in particular to administration forms for application on the skin or mucosa.
  • these transdermal/transmucosal administration forms are of a flat-shaped film structure and enable the administration of systemically active therapeutic agents via the skin or mucosa, it being possible to release said therapeutic agents to the skin or mucosa to be absorbed, continuously over a predetermined period of time and at a defined release rate.
  • the HME composition of the present invention is constituted so as to be disintegratable or degradable, the particles in the film can be released as such and subsequently the therapeutic agent contained in the particles can be released.
  • the particles are made of biodegradable material, the release may be influenced or accelerated by degradation of the particle material. In this way the present invention opens numerous possibilities of controlling the delivery of therapeutic agents.
  • the release of the therapeutic agents may also take place in such manner that the particles migrate or diffuse from the HME film through the skin or mucosa, and subsequently deliver the therapeutic agent to the circulation.
  • a method of drug delivery includes applying to a mucosal surface a hot melt extruded film composition, wherein the film composition includes at least one detackifier (e.g., silicon dioxide), polyethylene oxide, at least one additional polymer, at least one additive, and at least one therapeutic agent.
  • detackifier e.g., silicon dioxide
  • Example 1 Hot melt extrusion composition (with silicon oxide)

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Dermatology (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne une composition extrudée à chaud par coulée stratifiée mono ou multicouche comprenant du dioxyde de silicium, de l'oxyde de polyéthylène, au moins un polymère supplémentaire, et au moins un additif. Une composition extrudée à chaud par coulée stratifiée mono ou multicouche selon l’invention comprend en outre un agent thérapeutique. L'invention concerne en outre un procédé de traitement d'un mélange en un film mince comprenant les étapes consistant à : former un mélange comprenant du dioxyde de silicium, de l'oxyde de polyéthylène, au moins un polymère supplémentaire, et au moins un additif ; extruder ledit mélange en direction du haut d'une section de calandrage ; et enrouler le mélange en cylindres maîtres de film mince. L'invention concerne de plus un procédé d'administration de médicament comprenant l'application sur une surface muqueuse d'une composition fabriquée par extrusion à chaud par coulée, la composition d’extrusion comprenant un antiadhésif, au moins un polymère, au moins un additif, et un agent thérapeutique.
PCT/US2009/003455 2008-06-09 2009-06-08 Film extrudé à chaud par coulée contenant du dioxyde de silicium Ceased WO2009151574A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US13147108P 2008-06-09 2008-06-09
US61/131,471 2008-06-09

Publications (1)

Publication Number Publication Date
WO2009151574A1 true WO2009151574A1 (fr) 2009-12-17

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10835495B2 (en) 2012-11-14 2020-11-17 W. R. Grace & Co.-Conn. Compositions containing a biologically active material and a non-ordered inorganic oxide material and methods of making and using the same
US20230346693A1 (en) * 2017-06-28 2023-11-02 University Of Pittsburgh-Of The Commonwealth System Of Higher Education Hot melt extrusion for pharmaceutical vaginal film products

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5032450A (en) * 1990-01-31 1991-07-16 Ppg Industries, Inc. Microporous material having a coating of hydrophobic polymer
US6375963B1 (en) * 1999-06-16 2002-04-23 Michael A. Repka Bioadhesive hot-melt extruded film for topical and mucosal adhesion applications and drug delivery and process for preparation thereof
US20060251724A1 (en) * 2003-05-06 2006-11-09 Farrell Thomas P Method for preparing thermoformed compositions containing acrylic polymer binders, pharmaceutical dosage forms and methods of preparing the same
US20070020188A1 (en) * 2001-08-06 2007-01-25 Purdue Pharma L.P. Pharmaceutical formulation containing irritant
US20070148252A1 (en) * 2005-11-28 2007-06-28 Marinus Pharmaceuticals Solid ganaxolone formulations and methods for the making and use thereof

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5032450A (en) * 1990-01-31 1991-07-16 Ppg Industries, Inc. Microporous material having a coating of hydrophobic polymer
US6375963B1 (en) * 1999-06-16 2002-04-23 Michael A. Repka Bioadhesive hot-melt extruded film for topical and mucosal adhesion applications and drug delivery and process for preparation thereof
US20070020188A1 (en) * 2001-08-06 2007-01-25 Purdue Pharma L.P. Pharmaceutical formulation containing irritant
US20060251724A1 (en) * 2003-05-06 2006-11-09 Farrell Thomas P Method for preparing thermoformed compositions containing acrylic polymer binders, pharmaceutical dosage forms and methods of preparing the same
US20070148252A1 (en) * 2005-11-28 2007-06-28 Marinus Pharmaceuticals Solid ganaxolone formulations and methods for the making and use thereof

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10835495B2 (en) 2012-11-14 2020-11-17 W. R. Grace & Co.-Conn. Compositions containing a biologically active material and a non-ordered inorganic oxide material and methods of making and using the same
US20230346693A1 (en) * 2017-06-28 2023-11-02 University Of Pittsburgh-Of The Commonwealth System Of Higher Education Hot melt extrusion for pharmaceutical vaginal film products

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