CA2282906A1 - Stable complexes of poorly soluble compounds - Google Patents
Stable complexes of poorly soluble compounds Download PDFInfo
- Publication number
- CA2282906A1 CA2282906A1 CA002282906A CA2282906A CA2282906A1 CA 2282906 A1 CA2282906 A1 CA 2282906A1 CA 002282906 A CA002282906 A CA 002282906A CA 2282906 A CA2282906 A CA 2282906A CA 2282906 A1 CA2282906 A1 CA 2282906A1
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- Prior art keywords
- compound
- polymer
- ionic polymer
- insoluble
- therapeutically active
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- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
-
- 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
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dermatology (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Stable water-insoluble complexes of poorly soluble compounds molecularly dispersed in water-insoluble ionic polymers are disclosed. Useful insoluble ionic polymers have a molecular weight greater than about 80,000 D and a glass transition temperature equal to or greater than about 50°. The compounds are microprecipitated in the ionic polymers in amorphous form. The complexes according to the present invention significantly increase the bioavailability of poorly soluble therapeutically active compounds.
Claims (46)
1. A pharmaceutical composition comprising a water-insoluble complex of a therapeutically active, stable amorphous compound and a water-insoluble ionic polymer that has a molecular weight greater than about 80,000 D and a glass transition temperature equal to or greater than about 50°C, and a carrier.
2. The pharmaceutical composition of claim 1 wherein the therapeutically active compound is a compound that is poorly soluble when in crystalline form.
3. The pharmaceutical composition of claim 2 wherein the poorly soluble therapeutically active compound in its crystalline form has a solubility of less than 1 mg/mL in aqueous solution.
4. The pharmaceutical composition of claim 1 wherein the ionic polymer is a cationic polymer.
5. The pharmaceutical composition of claim 4 wherein the cationic polymer is a copolymer of dimethylaminoethylmethacrylate and neutral methacrylic ester.
6. The pharmaceutical composition of claim 5 wherein the cationic polymer is Eudragit E R.
7. The pharmaceutical composition of claim 1 wherein the ionic polymer is an anionic polymer.
8. The pharmaceutical composition of claim 7 wherein the anionic polymer is a copolymer of methacrylic acid and ethyl acrylate or methacrylic acid and methyl methacrylate.
9. The pharmaceutical composition of claim 8 wherein the anionic polymer is selected from the group consisting of Eudragit L 100-55R , Eudragit L-100R
and Eudragit S-100R.
and Eudragit S-100R.
10. The pharmaceutical composition of claim 7 wherein the anionic polymer is selected from the group consisting of polyvinyl acetate phthalate, cellulose acetate phthalate, hydroxypropylmethylcellulose phthalate, cellulose acetate terphthalate, polycyanoacrylate and hydroxypropyl methyl cellulose acetyl succinate, carboxy methyl cellulose, and low substituted hydroxypropylcellulose.
11. The pharmaceutical composition of claim 1 wherein the solubility of the ionic polymer is pH dependent.
12. The pharmaceutical composition of claim 11 wherein the ionic polymer is insoluble at pH above about 4.
13. The pharmaceutical composition of claim 1 wherein the ionic polymer and the therapeutically active compound in its crystalline form are both relatively insoluble above pH of about 4.
14. The pharmaceutical composition of claim 11 wherein the ionic polymer is insoluble at pH below about 4.
15. The pharmaceutical composition of claim 1 wherein the ionic polymer and the therapeutically active compound in its crystalline form are both relatively insoluble at pH below about 4.
16. The pharmaceutical composition of claim 1 wherein the therapeutically active compound is selected from the group consisting of Compounds I, II, III, IV, V, VI, VII and VIII.
17. A pharmaceutical composition comprising a water-insoluble complex of Compound I in stable amorphous form and a water-insoluble ionic polymer that has a molecular weight greater than about 80,000 D and a glass transition temperature equal to or greater than about 50°C, and a carrier.
18. The pharmaceutical composition of claim 1 wherein the ionic polymer is.
present in the water-insoluble complex at not less than about 20%, by weight.
present in the water-insoluble complex at not less than about 20%, by weight.
19. The pharmaceutical composition of claim 18 wherein the therapeutically active compound is present in the water-insoluble complex at about 0.1% to about 80%, by weight of said complex.
20. The pharmaceutical composition of claim 19 wherein the therapeutically active compound is present in the water-insoluble complex at about 30% to about 70%, by weight of said complex.
21. The pharmaceutical composition of claim 20 wherein the ionic polymer is present in the water-insoluble complex at about 50%, by weight, and the therapeutically active compound is present at about 50%, by weight of said complex.
22. A method for preparing a pharmaceutical formulation comprising a water-insoluble complex of a stable, amorphous therapeutically active compound and an ionic polymer comprising:
(a) dissolving the therapeutically active compound and ionic polymer in a suitable solvent;
(b) contacting the solution of step (a) with an aqueous solution at a pH in which the ionic polymer is poorly soluble thereby microprecipitation the therapeutically active compound and ionic polymer as a compound/polymer complex;
(c) preparing a pharmaceutical formulation that includes the compound/ polymer complex of step (b) above.
(a) dissolving the therapeutically active compound and ionic polymer in a suitable solvent;
(b) contacting the solution of step (a) with an aqueous solution at a pH in which the ionic polymer is poorly soluble thereby microprecipitation the therapeutically active compound and ionic polymer as a compound/polymer complex;
(c) preparing a pharmaceutical formulation that includes the compound/ polymer complex of step (b) above.
23. The method of claim 22, wherein in step (a), the therapeutically active compound and the ionic polymer are dissolved in a solvent selected from the group consisting of ethyl alcohol, methyl alcohol, dimethylsulfoxide, dimethylacetamide, dimethyl formamide, N-methylpyrrolidone, Transcutol R (diethylene glycol monoethyl ether, Gattefosse), glycofural, propylene carbonate, tetrahydrofuran, polyethylene glycol and propylene glycol.
24. The method in claim 22 wherein in step (b), microprecipitation is carried out by removing the solvent by spray drying or lyophilizing.
25. The method of claim 22 wherein in step (a), the insoluble therapeutically active and the ionic compound polymer are dissolved by adjusting the pH.
26. The method of claim 22 wherein after step (b), residual solvent is removed.
27. The method of claim 26 wherein the residual solvent is removed by washing the compound/polymer complex.
28. The method of claim 26 wherein the residual solvent is removed by evaporation or drying.
29. The method of claim 28 wherein the residual solvent is removed by spray drying.
30. A method for preparing a pharmaceutical formulation comprising a water-insoluble complex of a stable, amorphous therapeutically active compound and an ionic polymer comprising:
(a) dissolving the therapeutically active compound, in its crystalline form, and ionic polymer in an organic solvent;
(b) contacting the product of step (a) with an aqueous solution at a pH at which the ionic polymer and the therapeutically active compound will precipitate as a compound/polymer matrix;
(c) washing the compound/polymer matrix;
(d) drying the compound/polymer matrix; and (e) preparing a pharmaceutical formulation that incorporates the washed and dried compound/polymer matrix of step (d) above.
(a) dissolving the therapeutically active compound, in its crystalline form, and ionic polymer in an organic solvent;
(b) contacting the product of step (a) with an aqueous solution at a pH at which the ionic polymer and the therapeutically active compound will precipitate as a compound/polymer matrix;
(c) washing the compound/polymer matrix;
(d) drying the compound/polymer matrix; and (e) preparing a pharmaceutical formulation that incorporates the washed and dried compound/polymer matrix of step (d) above.
31. The method of claim 30 wherein the therapeutically active compound that is incorporated in the compound/polymer matrix is predominantly in amorphous form.
32. The method of claim 31 wherein the ionic polymer is selected from the group consisting of Eudragit R E100, Eudragit R L100, Eudragit R L100-55 and Eudragit R S100.
33. A method for preparing a water-insoluble complex of a stable amorphous compound and an ionic polymer comprising:
(a) melting together the therapeutically active compound and the ionic polymer; and (b) cooling the mixture resulting from step (a).
(a) melting together the therapeutically active compound and the ionic polymer; and (b) cooling the mixture resulting from step (a).
34. A method for preparing a pharmaceutical formulation comprising a water-insoluble complex of a stable amorphous compound and an ionic polymer comprising:
(a) dissolving the therapeutically active compound and the ionic polymer in a supercritical fluid;
(b) removing the supercritical fluid resulting in the microprecipitation of the therapeutically active compound in the polymer matrix; and (c) preparing a pharmaceutically formulation that includes the product of step (b) above.
(a) dissolving the therapeutically active compound and the ionic polymer in a supercritical fluid;
(b) removing the supercritical fluid resulting in the microprecipitation of the therapeutically active compound in the polymer matrix; and (c) preparing a pharmaceutically formulation that includes the product of step (b) above.
35. The method of claim 34 wherein the supercritical fluid used in step (a) is selected from the group consisting of liquid nitrogen and liquid carbon dioxide.
36. The method of claim 34 wherein removal of the supercritical fluid in step (b) is accomplished by evaporation.
37. The method of claim 22, 30, 33, 34 or 35 wherein the therapeutically active compound is selected from the group consisting of Compounds I, II, III, IV, V, VI, VII and VIII.
38. A stable, water-insoluble complex prepared by (a) dissolving Compound I and a water-insoluble ionic polymer having a molecular weight greater than 80,000D and a glass transition temperature equal to or greater than 50°C in a suitable solvent; and (b) co-precipitating Compound I and the ionic polymer as a compound/polymer complex.
39. The complex of claim 38 wherein precipitation in step (b) in effected by contacting the solution of step (a) with an aqueous solution at a pH in which the ionic polymer is poorly soluble.
40. A water-insoluble complex comprising a stable, amorphous compound and a water-insoluble ionic polymer that has a molecular weight greater than 80,000 D and a glass transition temperature equal to or greater than 50°C.
41. The complex of claim 40 wherein the amorphous compound is poorly soluble in crystalline form.
42. A water-insoluble complex comprising Compound I in stable amorphous form and a water-insoluble ionic polymer that has a molecular weight greater than 80,000 D and a glass transition temperature equal to or greater than 50°C.
43. A method for stabilizing an amorphous compound comprising molecularly dispersing the compound in a water-insoluble ionic polymer that has a molecular weight greater than 80,000 D and a glass transition temperature equal to or greater than 50°C.
44. A method for converting a poorly soluble, crystalline compound to a stable amorphous form of said compound comprising molecularly dispersing said compound in a water-insoluble ionic polymer that has a molecular weight greater than 80,000 D and a glass transition temperature equal to or greater than 50°C.
45. A therapeutically active compound in stable amorphous form molecularly dispersed in a water-insoluble ionic polymer that has a molecular weight greater than 80,000 D and a glass transition temperature equal to or greater than 50°C.
46. The invention as herein before described.
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10133698P | 1998-09-22 | 1998-09-22 | |
US60/101,336 | 1998-09-22 | ||
US13653199P | 1999-05-28 | 1999-05-28 | |
US60/136,531 | 1999-05-28 |
Publications (2)
Publication Number | Publication Date |
---|---|
CA2282906A1 true CA2282906A1 (en) | 2000-03-22 |
CA2282906C CA2282906C (en) | 2010-07-20 |
Family
ID=26798138
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA2282906A Expired - Lifetime CA2282906C (en) | 1998-09-22 | 1999-09-20 | Stable complexes of poorly soluble compounds |
Country Status (33)
Country | Link |
---|---|
US (1) | US6350786B1 (en) |
EP (1) | EP0988863B2 (en) |
JP (5) | JP2000095708A (en) |
KR (1) | KR100362019B1 (en) |
CN (1) | CN1201821C (en) |
AR (2) | AR022096A1 (en) |
AT (1) | ATE265232T1 (en) |
AU (1) | AU770745B2 (en) |
BR (1) | BR9904283A (en) |
CA (1) | CA2282906C (en) |
CO (1) | CO5140077A1 (en) |
CZ (1) | CZ300215B6 (en) |
DE (1) | DE69916733T3 (en) |
DK (1) | DK0988863T4 (en) |
ES (1) | ES2218918T5 (en) |
HK (1) | HK1026632A1 (en) |
HR (1) | HRP990287B1 (en) |
HU (1) | HU228341B1 (en) |
ID (1) | ID24034A (en) |
IL (1) | IL131957A (en) |
MA (1) | MA26692A1 (en) |
MY (1) | MY124377A (en) |
NO (1) | NO326928B1 (en) |
NZ (1) | NZ337884A (en) |
PE (1) | PE20001049A1 (en) |
PL (1) | PL202757B1 (en) |
PT (1) | PT988863E (en) |
RS (1) | RS50193B (en) |
RU (1) | RU2240827C2 (en) |
SG (1) | SG97131A1 (en) |
SI (1) | SI0988863T2 (en) |
TR (1) | TR199902324A3 (en) |
TW (1) | TWI234465B (en) |
Families Citing this family (85)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE60039379D1 (en) | 1999-02-10 | 2008-08-21 | Pfizer Prod Inc | Pharmaceutical solid dispersions |
US6440959B1 (en) | 1999-04-21 | 2002-08-27 | Hoffman-La Roche Inc. | Pyrazolobenzodiazepines |
PE20010659A1 (en) * | 1999-10-01 | 2001-06-20 | Hoffmann La Roche | DERIVATIVES OF PYRIMIDIN-2,4,6-TRIONAS AS INHIBITORS OF METALOPROTEASES |
US6313143B1 (en) * | 1999-12-16 | 2001-11-06 | Hoffmann-La Roche Inc. | Substituted pyrroles |
WO2001087368A1 (en) * | 2000-05-16 | 2001-11-22 | Ortho-Mcneil Pharmaceutical, Inc. | Process for coating medical devices using super-critical carbon dioxide |
US6482847B2 (en) | 2000-10-03 | 2002-11-19 | Hoffmann-La Roche Inc. | Amorphous form of cell cycle inhibitor having improved solubility and bioavailability |
US6469179B1 (en) | 2000-10-03 | 2002-10-22 | Hoffmann-La Roche Inc. | Amorphous form of cell cycle inhibitor having improved solubility and bioavailability |
US8067032B2 (en) | 2000-12-22 | 2011-11-29 | Baxter International Inc. | Method for preparing submicron particles of antineoplastic agents |
US9700866B2 (en) | 2000-12-22 | 2017-07-11 | Baxter International Inc. | Surfactant systems for delivery of organic compounds |
US20050048126A1 (en) | 2000-12-22 | 2005-03-03 | Barrett Rabinow | Formulation to render an antimicrobial drug potent against organisms normally considered to be resistant to the drug |
US6548531B2 (en) | 2001-02-09 | 2003-04-15 | Hoffmann-La Roche Inc. | Method for cancer therapy |
US6716845B2 (en) | 2001-03-30 | 2004-04-06 | Hoffmann-La Roche Inc. | Barbituric acid derivatives |
BR0210000A (en) * | 2001-05-30 | 2004-05-04 | Csir | Method of encapsulating an active substance |
US20030044514A1 (en) * | 2001-06-13 | 2003-03-06 | Richard Robert E. | Using supercritical fluids to infuse therapeutic on a medical device |
WO2002102373A1 (en) * | 2001-06-15 | 2002-12-27 | F. Hoffmann-La Roche Ag | Method for administration of cancer therapeutic |
JP2004534812A (en) | 2001-06-22 | 2004-11-18 | ファイザー・プロダクツ・インク | Pharmaceutical composition of dispersion of drug and neutral polymer |
MXPA03011933A (en) | 2001-06-22 | 2004-03-26 | Pfizer Prod Inc | Pharmaceutical compositions comprising low-solubility and/or acid-sensitive drugs and neutralized acidic polymers. |
CA2461349C (en) | 2001-09-26 | 2011-11-29 | Baxter International Inc. | Preparation of submicron sized nanoparticles via dispersion and solvent or liquid phase removal |
US20060003012A9 (en) | 2001-09-26 | 2006-01-05 | Sean Brynjelsen | Preparation of submicron solid particle suspensions by sonication of multiphase systems |
US20030139373A1 (en) * | 2001-11-20 | 2003-07-24 | Breimer Lars Holger | Method for cancer therapy |
BR0307333A (en) | 2002-02-01 | 2004-12-07 | Pfizer Prod Inc | Methods for preparing homogeneous dispersions of atomized amorphous solid drugs using a spray drying system |
MXPA05000977A (en) | 2002-08-12 | 2005-05-16 | Pfizer Prod Inc | Pharmaceutical compositions of semi-ordered drugs and polymers. |
DE10351087A1 (en) * | 2003-10-31 | 2005-05-25 | Bayer Technology Services Gmbh | Solid active ingredient formulation |
DK1683524T3 (en) | 2003-11-14 | 2011-03-14 | Ajinomoto Kk | Solid-form dispersion or phenyalanine derivative solid form medical preparation |
WO2005046697A1 (en) * | 2003-11-14 | 2005-05-26 | Ajinomoto Co., Inc. | Sustained-release phenylalanine derivative preparation for oral administration |
US20070191404A1 (en) * | 2004-04-01 | 2007-08-16 | Pierre Bartsch | Pharmaceutical compositions of pyrimidine-2,4,6-triones |
AR049915A1 (en) * | 2004-06-14 | 2006-09-13 | Anacor Pharmaceuticals Inc | COMPOUNDS WITH BORO CONTENT AND METHODS OF USE OF THE SAME |
WO2006062980A2 (en) * | 2004-12-07 | 2006-06-15 | Nektar Therapeutics | Stable non-crystalline formulation comprising tiagabine |
WO2006070845A1 (en) * | 2004-12-28 | 2006-07-06 | Eisai R & D Management Co., Ltd. | Quick disintegration tablet and method of producing the same |
DK1848430T3 (en) * | 2004-12-31 | 2017-11-06 | Dr Reddys Laboratories Ltd | NEW BENZYLAMINE DERIVATIVES AS CETP INHIBITORS |
US8604055B2 (en) | 2004-12-31 | 2013-12-10 | Dr. Reddy's Laboratories Ltd. | Substituted benzylamino quinolines as cholesterol ester-transfer protein inhibitors |
EP1690528A1 (en) * | 2005-02-11 | 2006-08-16 | Abbott GmbH & Co. KG | Process for the preparation of dosage forms comprising a solid dispersion of a microcrystalline active agent |
CA2608952A1 (en) * | 2005-05-19 | 2006-11-23 | Dwayne Thomas Friesen | Pharmaceutical compostions comprising an amorphous form of a vegf-r inhibitor |
EP1767194A1 (en) * | 2005-06-09 | 2007-03-28 | Helm AG | Process for the preparation of adsorbates of drospirenone |
ES2371397T3 (en) * | 2005-06-22 | 2011-12-30 | Plexxikon, Inc. | PIRROLO DERIVATIVES [2,3-B] PIRIDINE AS INHIBITORS OF PROTEIN KINES. |
US20080031944A1 (en) * | 2006-08-04 | 2008-02-07 | Cima Labs Inc. | Stabilization of lorazepam |
UY30535A1 (en) * | 2006-08-10 | 2008-03-31 | Cipla Ltd | COMPOSITION UNDERSTANDING ANTIRRETROVIRAL PHARMACOS AND AT LEAST AN INSOLUBLE WATER POLYMER, PREPARATION PROCESS AND APPLICATIONS. |
US20080107725A1 (en) * | 2006-10-13 | 2008-05-08 | Albano Antonio A | Pharmaceutical Solid Dosage Forms Comprising Amorphous Compounds Micro-Embedded in Ionic Water-Insoluble Polymers |
WO2008063888A2 (en) | 2006-11-22 | 2008-05-29 | Plexxikon, Inc. | Compounds modulating c-fms and/or c-kit activity and uses therefor |
PE20121126A1 (en) * | 2006-12-21 | 2012-08-24 | Plexxikon Inc | PIRROLO [2,3-B] PYRIDINES COMPOUNDS AS KINASE MODULATORS |
WO2008079909A1 (en) * | 2006-12-21 | 2008-07-03 | Plexxikon, Inc. | Pyrrolo [2,3-b] pyridines as kinase modulators |
US20080221047A1 (en) * | 2006-12-27 | 2008-09-11 | Astellas Pharma Inc., | Aminoakyl methacrylate copolymer E for maintaining solubility of poorly-soluble drug |
WO2008138755A2 (en) * | 2007-05-11 | 2008-11-20 | F. Hoffmann-La Roche Ag | Pharmaceutical compositions for poorly soluble drugs |
US8722736B2 (en) | 2007-05-22 | 2014-05-13 | Baxter International Inc. | Multi-dose concentrate esmolol with benzyl alcohol |
US8426467B2 (en) | 2007-05-22 | 2013-04-23 | Baxter International Inc. | Colored esmolol concentrate |
EP1997479A1 (en) * | 2007-05-31 | 2008-12-03 | Helm AG | Stabilized amorphous candesartan cilexetil compositions for oral administration |
AU2008276063B2 (en) | 2007-07-17 | 2013-11-28 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
CN101896161A (en) * | 2007-10-19 | 2010-11-24 | 普渡(大学)研究基金 | Solid formulations of crystalline compounds |
US8632805B2 (en) * | 2008-06-20 | 2014-01-21 | Mutual Pharmaceutical Company, Inc. | Controlled-release formulations, method of manufacture, and use thereof |
US7794750B2 (en) * | 2008-06-20 | 2010-09-14 | Mutual Pharmaceutical Company, Inc. | Controlled-release formulations, method of manufacture, and use thereof |
WO2010044842A1 (en) * | 2008-10-16 | 2010-04-22 | University Of Tennessee Research Foundation | Tamper resistant oral dosage forms containing an embolizing agent |
KR20100073454A (en) * | 2008-12-23 | 2010-07-01 | 국립암센터 | Novel pyrazolodiazepine compound as an transglutaminase inhibitor, the preparation method thereof and a composition containing the same |
AR078033A1 (en) * | 2009-04-03 | 2011-10-12 | Plexxikon Inc | A SOLID DISPERSION, CONTAINING THE COMPOUND {3- [5- (4- (CHLORINE-PHENYL) -1H-PIRROLO [2,3-B] PIRIDINA-3-CARBONIL] -2,4-DIFLUOR-PHENIL} -AMIDA OF PROPANE-1-SULPHONIC ACID, COMPOSITIONS AND FORMULATIONS THAT INCLUDE SUCH SOLID DISPERSION; METHODS FOR MANUFACTURING SUCH SOLID DISPERSION, FORMS 1 AND 2 |
US8329724B2 (en) | 2009-08-03 | 2012-12-11 | Hoffmann-La Roche Inc. | Process for the manufacture of pharmaceutically active compounds |
NZ599866A (en) | 2009-11-06 | 2014-09-26 | Plexxikon Inc | Compounds and methods for kinase modulation, and indications therefor |
WO2011152297A1 (en) * | 2010-05-31 | 2011-12-08 | アステラス製薬株式会社 | Solid dispersion comprising triazole compound |
PE20141360A1 (en) | 2011-02-07 | 2014-10-13 | Plexxikon Inc | COMPOUNDS AND METHODS FOR THE MODULATION OF KINASES AND INDICATIONS FOR THEM. |
WO2012110469A1 (en) | 2011-02-17 | 2012-08-23 | F. Hoffmann-La Roche Ag | A process for controlled crystallization of an active pharmaceutical ingredient from supercooled liquid state by hot melt extrusion |
TWI558702B (en) | 2011-02-21 | 2016-11-21 | 普雷辛肯公司 | Solid forms of a pharmaceutically active substance |
CA2845284C (en) | 2011-08-18 | 2018-03-06 | Dr. Reddy's Laboratories Ltd. | Substituted heterocyclic amine compounds as cholesteryl ester-transfer protein (cetp) inhibitors |
WO2013037396A1 (en) * | 2011-09-12 | 2013-03-21 | Bioneer A/S | Solution of polymer in api for a solid dosage form |
WO2013046045A1 (en) | 2011-09-27 | 2013-04-04 | Dr. Reddy's Laboratories, Ltd. | 5 - benzylaminomethyl - 6 - aminopyrazolo [3, 4 -b] pyridine derivatives as cholesteryl ester -transfer protein (cetp) inhibitors useful for the treatment of atherosclerosis |
WO2013056108A2 (en) * | 2011-10-14 | 2013-04-18 | Array Biopharma Inc. | Solid dispersion |
CA2867723C (en) | 2012-03-23 | 2022-11-08 | Array Biopharma Inc. | Treatment of brain cancer |
US20140128431A1 (en) | 2012-04-03 | 2014-05-08 | Hoffmann-Laroche Inc. | Pharmaceutical composition with improved bioavailability, safety and tolerability |
EP2649989B1 (en) | 2012-04-13 | 2017-10-18 | King Saud University | Method for preparing a solid dispersion, solid dispersion obtained thereby and use thereof |
US9150570B2 (en) | 2012-05-31 | 2015-10-06 | Plexxikon Inc. | Synthesis of heterocyclic compounds |
JO3339B1 (en) * | 2012-09-11 | 2019-03-13 | Shanghai Inst Pharmaceutical Ind | Stabilised amorphous form of agomelatine, a process for its preparation and pharmaceutical compositions containing it |
BR112015011515A2 (en) | 2012-11-19 | 2017-08-22 | Dr Reddy´S Laboratories Ltd | PHARMACEUTICAL COMPOSITIONS OF CETP INHIBITORS |
RU2015128794A (en) | 2012-12-20 | 2017-01-25 | КАШИВ ФАРМА, ЭлЭлСи | COMPOSITION OF ORAL DECOMPOSABLE TABLETS, ENSURING INCREASED BIOAVAILABILITY |
BR112015015758B1 (en) | 2013-01-22 | 2022-01-04 | F. Hoffmann-La Roche Ag | SOLID DISPERSION, SOLID UNIT DOSE FORMULATION, PHARMACEUTICAL PREPARATION AND USE OF A SOLID DISPERSION |
TWI615157B (en) | 2013-02-06 | 2018-02-21 | 大塚製藥股份有限公司 | Solid dispersion comprising amorphous cilostazol |
US20160213575A1 (en) * | 2013-09-11 | 2016-07-28 | 3M Innovative Properties Company | Coating compositions, dental structures thereof and methods for generating contrast |
US20160303102A1 (en) * | 2013-12-05 | 2016-10-20 | Alrise Biosystems Gmbh | Process for the production of drug formulations for oral administration |
PT107846B (en) * | 2014-08-01 | 2019-03-22 | Hovione Farm S A | Production of Amorphous Solid Dispersion Nanoparticles by Controlled Co-Precipitation |
BR112017025739A2 (en) * | 2015-05-29 | 2018-08-07 | Sun Pharmaceutical Ind Ltd | isotretinoin oral pharmaceutical composition having increased bioavailability, process for preparing it and method of treatment |
BR112019008295B1 (en) * | 2016-12-13 | 2024-03-12 | TransThera Sciences (Nanjing), Inc | MULTIKINASE INHIBITOR COMPOUND, CRYSTALLINE FORM OF THE COMPOUND OF FORMULA III, PHARMACEUTICAL FORMULATION/COMPOSITION, ITS USES, METHODS FOR THE PREPARATION OF THE CRYSTALLINE FORM AND THE COMPOUND OF FORMULA III AND INTERMEDIATE FOR THE PREPARATION OF THE COMPOUND OF FORMULA III |
CA3060407A1 (en) | 2017-04-28 | 2018-11-01 | Seattle Genetics, Inc. | Treatment of her2 positive cancers |
KR102082775B1 (en) * | 2017-05-02 | 2020-02-28 | 주식회사 삼양바이오팜 | Formulation with enhanced water solubility and bioavailability |
RU2725879C2 (en) * | 2018-07-26 | 2020-07-07 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Казанский Государственный медицинский университет" Министерства здравоохранения Российской Федерации | Interpolymer carrier for oral systems of controlled delivery of active pharmaceutical ingredients |
US11535600B2 (en) | 2018-12-03 | 2022-12-27 | H. Lundbeck A/S | Prodrugs of 4-((1R,3S)-6-chloro-3-phenyl-2,3-dihydro-1H-inden-1-yl)-1,2,2-trimethylpiperazine and 4-((1R,3S)-6-chloro-3-(phenyl-d5)-2,3-dihydro-1H-inden-1-yl)-2,2-dimethyl-1-(methyl-d3)piperazine |
WO2021150981A1 (en) | 2020-01-24 | 2021-07-29 | Nanocopoeia, Llc | Amorphous solid dispersions of dasatinib and uses thereof |
CA3168680A1 (en) | 2020-01-31 | 2021-08-05 | Nanocopoeia, Llc | Amorphous nilotinib microparticles and uses thereof |
EP4116389A4 (en) | 2020-03-03 | 2024-03-20 | Dexerials Corp | Method for manufacturing image display device |
EP4142699A1 (en) | 2020-04-30 | 2023-03-08 | Nanocopoeia LLC | Orally disintegrating tablet comprising amorphous solid dispersion of nilotinib |
Family Cites Families (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS51118816A (en) * | 1975-04-08 | 1976-10-19 | Meiji Seika Kaisha Ltd | A process for stabilizing non-crystalloidal solid |
US4344934A (en) * | 1978-11-20 | 1982-08-17 | American Home Products Corporation | Therapeutic compositions with enhanced bioavailability |
DK569786A (en) * | 1985-11-27 | 1987-05-28 | Syntex Inc | benzimidazole |
CZ280738B6 (en) * | 1988-02-10 | 1996-04-17 | F. Hoffmann - La Roche And Co., Aktiengesellschaft | Substituted pyrroles, their use for preparing medicaments and medicaments based thereon |
JP2528706B2 (en) † | 1988-05-30 | 1996-08-28 | ゼリア新薬工業株式会社 | Pharmaceutical composition of dihydropyridine compound |
USRE36736E (en) | 1989-02-06 | 2000-06-13 | Hoffman-La Roche Inc. | Substituted pyrroles |
JPH0729926B2 (en) † | 1989-07-25 | 1995-04-05 | 大塚製薬株式会社 | Composition for easily absorbable preparations |
US5399363A (en) | 1991-01-25 | 1995-03-21 | Eastman Kodak Company | Surface modified anticancer nanoparticles |
ATE159426T1 (en) † | 1991-04-16 | 1997-11-15 | Nippon Shinyaku Co Ltd | METHOD FOR PRODUCING A SOLID DISPERSION |
US5281420A (en) | 1992-05-19 | 1994-01-25 | The Procter & Gamble Company | Solid dispersion compositions of tebufelone |
TW493991B (en) | 1995-05-08 | 2002-07-11 | Novartis Ag | Pharmaceutical composition for oral administration of active agent having low water solubility and process for preparation of the same |
GB9511220D0 (en) † | 1995-06-02 | 1995-07-26 | Glaxo Group Ltd | Solid dispersions |
DE69628276T2 (en) * | 1995-07-26 | 2004-04-08 | Kyowa Hakko Kogyo Co., Ltd. | PREPARATION OF XANTHINE DERIVATIVES AS A FIXED DISPERSION |
EP0952770A4 (en) † | 1995-09-07 | 1999-12-22 | Fuisz Technologies Ltd | System for rendering substantially non-dissoluble bio-affecting agents bio-available |
DE19548624A1 (en) | 1995-12-23 | 1997-06-26 | Boehringer Mannheim Gmbh | New barbituric acid derivatives, processes for their preparation and medicaments containing these compounds |
JPH09208459A (en) * | 1996-02-07 | 1997-08-12 | Eisai Co Ltd | Preparation improved in solubility |
CZ297979B6 (en) | 1996-03-12 | 2007-05-16 | Pg-Txl Company, L. P. | Composition comprising anti-tumor medicament conjugated to water-soluble polymer, its use in the preparation of a medicament and implantable medical device |
EP0954288B1 (en) * | 1996-06-28 | 2004-08-11 | Schering Corporation | Solid solution of an antifungal agent with enhanced bioavailability |
PE91598A1 (en) | 1996-07-29 | 1998-12-24 | Hoffmann La Roche | SUBSTITUTED PYRROLES |
US6229011B1 (en) | 1997-08-22 | 2001-05-08 | Hoffman-La Roche Inc. | N-aroylphenylalanine derivative VCAM-1 inhibitors |
IL138247A (en) | 1998-03-17 | 2005-08-31 | Hoffmann La Roche | Substituted bisindolymaleimides for the inhibition of cell proliferation and pharmaceutical compositions comprising them |
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