US2007218012A1PendingUtilityA1

Pharmaceutical Compositions

44
Individually held — no corporate assignee on recordPriority: Mar 20, 2006Filed: Mar 19, 2007Published: Sep 20, 2007
Est. expiryMar 20, 2026(expired)· nominal 20-yr term from priority
Inventors:Kevin John BittorfJeffrey P. KatstraFilipe Gaspar
A61P 31/12A61P 31/14A61P 43/00A61K 9/12A61K 47/20A61K 47/38A61K 9/14A61K 31/12A61K 9/16A61K 9/19A61K 9/1652A61K 9/1694
44
PatentIndex Score
0
Cited by
0
References
0
Claims

Abstract

Methods of spray drying are described.

Claims

exact text as granted — not AI-modified
1 . A method of spray drying a drug, the method comprising forming or providing a mixture of the drug in a solvent system that comprises a solvent or combination of components where at least one solvent is a non-volatile solvent to form a mixture of the drug and solvent, and spray-drying the mixture to obtain amorphous drug product, with the proviso that the drug is other than N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide.  
     
     
         2 . The method of  claim 1 , wherein the mixture comprises a solution or a suspension.  
     
     
         3 . The method of  claim 1 , wherein the drug is a small molecule drug, for example a drug having a molecular weight of less than about 1000 daltons.  
     
     
         4 . The method of  claim 1 , wherein the drug is a poorly soluble drug.  
     
     
         5 . The method of  claim 1 , wherein the drug is selected from one of the following classifications: analgesics, anti-inflammatory agents, antihelminthics, anti-arrhythmic agents, anti-bacterial agents, anti-viral agents, anti-coagulants, anti-depressants, anti-diabetics, anti-epileptics, anti-fungal agents, anti-gout agents, anti-hypertensive agents, anti-malarials, anti-migraine agents, anti-muscarinic agents, anti-neoplastic agents, erectile dysfunction improvement agents, immunosuppressants, anti-protozoal agents, anti-thyroid agents, anxiolytic agents, sedatives, hypnotics, neuroleptics, β-blockers, cardiac inotropic agents, corticosteroids, diuretics, anti-parkinsonian agents, gastro-intestinal agents, histamine receptor antagonists, keratolyptics, lipid regulating agents, anti-anginal agents, Cox-2 inhibitors, leukotriene inhibitors, macrolides, muscle relaxants, nutritional agents, opiod analgesics, protease inhibitors, sex hormones, stimulants, muscle relaxants, anti-osteoporosis agents, anti-obesity agents, cognition enhancers, anti-urinary incontinence agents, nutritional oils, anti-benign prostate hypertrophy agents, essential fatty acids, or non-essential fatty acids.  
     
     
         6 . The method of  claim 1 , wherein the drug comprises an anti-viral agent.  
     
     
         7 . The method of  claim 6 , wherein the anti-viral agent is used to treat Hepatitis C (HepC).  
     
     
         8 . The method of  claim 7 , wherein the anti-viral agent comprises a HepC protease inhibitor.  
     
     
         9 . The method of  claim 8 , wherein the HepC protease inhibitor comprises VX-950.  
     
     
         10 . The method of  claim 1 , wherein the solvent system comprises a combination of components comprising at least one non-volatile solvent.  
     
     
         11 . The method of  claim 10 , wherein the combination of components comprises a volatile solvent and a non-volatile solvent.  
     
     
         12 . The method of  claim 11 , wherein the volatile solvent comprises methylene chloride, acetone, chloroform, or THF.  
     
     
         13 . The method of  claim 11 , wherein the non-volatile solvent comprises glacial acetic acid, DMSO, DMF, or water.  
     
     
         14 . The method of  claim 11 , wherein the non-volatile solvent is present in an amount of from about 0.1% to about 20% by wt.  
     
     
         15 . The method of  claim 11 , wherein the solvent system comprises a combination of volatile solvents with a non-volatile solvent.  
     
     
         16 . The method of  claim 15 , wherein the volatile solvents comprise methylene chloride and acetone.  
     
     
         17 . The method of  claim 15 , wherein the non-volatile solvent comprises glacial acetic acid.  
     
     
         18 . The method of  claim 15 , wherein the solvent system comprises methylene chloride, acetone, and glacial acetic acid.  
     
     
         19 . The method of  claim 18 , wherein the solvent system comprises from about 40% to about 80% methylene chloride, from about 20% to about 35% acetone, and from about 0.1% to about 15% glacial acetic acid.  
     
     
         20 . The method of  claim 15 , wherein the non-volatile solvent comprises water.  
     
     
         21 . The method of  claim 15 , wherein the solvent system comprises methylene chloride, acetone, and water.  
     
     
         22 . The method of  claim 21 , wherein the solvent system comprises from about 40% to about 80% methylene chloride, from about 20% to about 35% acetone, and from about 0.1% to about 15% water.  
     
     
         23 . The method of  claim 1 , wherein the solvent system comprises glacial acetic acid.  
     
     
         24 . The method of  claim 1 , wherein the solvent system comprises water.  
     
     
         25 . The method of  claim 1 , wherein the mixture comprises a surfactant.  
     
     
         26 . The method of  claim 25 , wherein the surfactant comprises sodium lauryl sulfate (SLS) or Vitamin E or a derivative thereof.  
     
     
         27 . A method of forming a solid dispersion that comprises a drug and one or more polymers, the method comprising forming or providing a mixture of the drug and the one or more polymers in a solvent or combination of solvents wherein at least one solvent is a non-volatile solvent to form a mixture of the drug, one or more polymers and solvent; and spray-drying the mixture to obtain a solid dispersion.  
     
     
         28 . The method of  claim 27 , wherein the mixture is a solution or a suspension.  
     
     
         29 . The method of  claim 27 , wherein the solid dispersion is an amorphous solid dispersion.  
     
     
         30 . The method of  claim 27 , wherein the mixture comprises one or more water-soluble polymer or partially water-soluble polymer.  
     
     
         31 . The method of  claim 30 , wherein the water-soluble or partially water-soluble polymer is a cellulose derivative; ethylcellulose; polyvinylpyrrolidones (PVP); a polyethylene glycol (PEG); a polyvinyl alcohol (PVA); an acrylate; or a cyclodextrin or copolymer and derivative thereof.  
     
     
         32 . The method of  claim 30 , wherein the water-soluble or partially water-soluble polymer is hydroxypropylmethylcellulose (HPMC).  
     
     
         33 . The method of  claim 27 , wherein the mixture comprises a pH-dependent enteric polymer.  
     
     
         34 . The method of  claim 33 , wherein the pH-dependent enteric polymer is a cellulose derivative; a hydroxypropyl methyl cellulose phthalate (HPMCP); hydroxypropyl methyl cellulose acetate succinate (HPMCAS); carboxymethylcellulose (CMC) or a salt thereof, cellulose acetate trimellitate (CAT); hydroxypropylcellulose acetate phthalate (HPCAP); hydroxypropylmethyl-cellulose acetate phthalate (HPMCAP); methylcellulose acetate phthalate (MCAP); or a polymethacrylate.  
     
     
         35 . The method of  claim 34 , wherein the polymer is hydroxypropyl methyl cellulose acetate succinate (HPMCAS).  
     
     
         36 . The method of  claim 27 , wherein the mixture comprises an insoluble cross-linked polymer.  
     
     
         37 . The method of  claim 27 , wherein the mixture comprises a polyvinylpyrrolidone (PVP).  
     
     
         38 . The method of  claim 27 , wherein the mixture comprises a mixture of two or more polymers.  
     
     
         39 . The method of  claim 38 , wherein the mixture of two or more polymers comprises two cellulosic polymers.  
     
     
         40 . The method of  claim 39 , wherein the mixture of two or more polymers comprises HPMC and HPMCAS.  
     
     
         41 . The method of  claim 27 , wherein the one or more polymers are present in an amount of from about 30% to about 70% by weight in the solid dispersion.  
     
     
         42 . The method of  claim 27 , wherein the drug is a small molecule drug, for example a drug having a molecular weight of less than about 1000 daltons.  
     
     
         43 . The method of  claim 27 , wherein the drug is a poorly soluble drug.  
     
     
         44 . The method of  claim 27 , wherein the drug is selected from one of the following classifications: analgesics, anti-inflammatory agents, antihelminthics, anti-arrhythmic agents, anti-bacterial agents, anti-viral agents, anti-coagulants, anti-depressants, anti-diabetics, anti-epileptics, anti-fungal agents, anti-gout agents, anti-hypertensive agents, anti-malarials, anti-migraine agents, anti-muscarinic agents, anti-neoplastic agents, erectile dysfunction improvement agents, immunosuppressants, anti-protozoal agents, anti-thyroid agents, anxiolytic agents, sedatives, hypnotics, neuroleptics, β-blockers, cardiac inotropic agents, corticosteroids, diuretics, anti-parkinsonian agents, gastro-intestinal agents, histamine receptor antagonists, keratolyptics, lipid regulating agents, anti-anginal agents, Cox-2 inhibitors, leukotriene inhibitors, macrolides, muscle relaxants, nutritional agents, opiod analgesics, protease inhibitors, sex hormones, stimulants, muscle relaxants, anti-osteoporosis agents, anti-obesity agents, cognition enhancers, anti-urinary incontinence agents, nutritional oils, anti-benign prostate hypertrophy agents, essential fatty acids, or non-essential fatty acids.  
     
     
         45 . The method of  claim 27 , wherein the drug comprises an anti-viral agent.  
     
     
         46 . The method of  claim 45 , wherein the anti-viral agent is used to treat Hepatitis C (HepC).  
     
     
         47 . The method of  claim 46 , wherein the anti-viral agent comprises a HepC protease inhibitor.  
     
     
         48 . The method of  claim 47 , wherein the HepC protease inhibitor comprises VX-950.  
     
     
         49 . The method of  claim 27 , wherein the solvent or combination of solvents comprises a combination of components comprising at least one non-volatile solvent.  
     
     
         50 . The method of  claim 49 , wherein the combination of components comprises a volatile solvent and a non-volatile solvent.  
     
     
         51 . The method of  claim 50 , wherein the volatile solvent comprises methylene chloride, acetone, chloroform, or THF.  
     
     
         52 . The method of  claim 50 , wherein the non-volatile solvent comprises glacial acetic acid, DMSO, DMF, or water.  
     
     
         53 . The method of  claim 50 , wherein the non-volatile solvent is present in an amount of from about 0.1% to about 20% by wt.  
     
     
         54 . The method of  claim 50 , wherein the solvent system comprises a combination of volatile solvents with a non-volatile solvent.  
     
     
         55 . The method of  claim 54 , wherein the volatile solvents comprise methylene chloride and acetone.  
     
     
         56 . The method of  claim 54 , wherein the non-volatile solvent comprises glacial acetic acid.  
     
     
         57 . The method of  claim 54 , wherein the solvent or combination of solvents comprises methylene chloride, acetone, and glacial acetic acid.  
     
     
         58 . The method of  claim 57 , wherein the solvent or combination of solvents comprises from about 40% to about 80% methylene chloride, from about 20% to about 35% acetone, and from about 0.1% to about 15% glacial acetic acid.  
     
     
         59 . The method of  claim 54 , wherein the non-volatile solvent comprises water.  
     
     
         60 . The method of  claim 54 , wherein the solvent or combination of solvents comprises methylene chloride, acetone, and water.  
     
     
         61 . The method of  claim 60 , wherein the solvent or combination of solvents comprises from about 40% to about 80% methylene chloride, from about 20% to about 35% acetone, and from about 0.1% to about 15% water.  
     
     
         62 . The method of  claim 27 , wherein the solvent or combination of solvents comprises glacial acetic acid.  
     
     
         63 . The method of  claim 27 , wherein the solvent or combination of solvents comprises water.  
     
     
         64 . The method of  claim 27 , wherein the mixture comprises a surfactant.  
     
     
         65 . The method of  claim 64 , wherein the surfactant comprises sodium lauryl sulfate (SLS) or Vitamin E or a derivative thereof.  
     
     
         66 . A process comprising 
 a) forming or providing a mixture of a poorly water soluble drug, one or more polymers, and a solvent system comprising at least one non-volatile solvent; and    b) spray-drying the mixture to form a solid dispersion comprising a poorly water soluble drug to obtain a solid dispersion of the drug.    
     
     
         67 . The method of  claim 66 , wherein the one or more polymers comprise one or more water-soluble polymer or partially water-soluble polymer.  
     
     
         68 . The method of  claim 67 , wherein the water-soluble or partially water-soluble polymer is a cellulose derivative; ethylcellulose; polyvinylpyrrolidones (PVP); a polyethylene glycol (PEG); a polyvinyl alcohol (PVA); an acrylate; or a cyclodextrin or copolymer and derivative thereof.  
     
     
         69 . The method of  claim 67 , wherein the water-soluble or partially water-soluble polymer is hydroxypropylmethylcellulose (HPMC).  
     
     
         70 . The method of  claim 66 , wherein the one or more polymers comprise a pH-dependent enteric polymer.  
     
     
         71 . The method of  claim 70 , wherein the pH-dependent enteric polymer is a cellulose derivative; a hydroxypropyl methyl cellulose phthalate (HPMCP); hydroxypropyl methyl cellulose acetate succinate (HPMCAS); carboxymethylcellulose (CMC) or a salt thereof, cellulose acetate trimellitate (CAT); hydroxypropylcellulose acetate phthalate (HPCAP); hydroxypropylmethyl-cellulose acetate phthalate (HPMCAP); methylcellulose acetate phthalate (MCAP); or a polymethacrylate.  
     
     
         72 . The method of  claim 71 , wherein the polymer is hydroxypropyl methyl cellulose acetate succinate (HPMCAS).  
     
     
         73 . The method of  claim 66 , wherein the one or more polymers comprise an insoluble cross-linked polymer.  
     
     
         74 . The method of  claim 66 , wherein the one or more polymers comprise a polyvinylpyrrolidone (PVP).  
     
     
         75 . The method of  claim 66 , wherein the mixture comprises a mixture of two or more polymers.  
     
     
         76 . The method of  claim 75 , wherein the mixture of two or more polymers comprises two cellulosic polymers  
     
     
         77 . The method of  claim 76 , wherein the mixture of two or more polymers comprises HPMC and HPMCAS.  
     
     
         78 . The method of  claim 66 , wherein the one or more polymers are present in an amount of from about 30% to about 90% by weight in the solid dispersion.  
     
     
         79 . The method of  claim 66 , wherein the drug is a small molecule drug, for example a drug having a molecular weight of less than about 1000 daltons.  
     
     
         80 . The method of  claim 66 , wherein the drug is selected from one of the following classifications: analgesics, anti-inflammatory agents, antihelminthics, anti-arrhythmic agents, anti-bacterial agents, anti-viral agents, anti-coagulants, anti-depressants, anti-diabetics, anti-epileptics, anti-fungal agents, anti-gout agents, anti-hypertensive agents, anti-malarials, anti-migraine agents, anti-muscarinic agents, anti-neoplastic agents, erectile dysfunction improvement agents, immunosuppressants, anti-protozoal agents, anti-thyroid agents, anxiolytic agents, sedatives, hypnotics, neuroleptics, β-blockers, cardiac inotropic agents, corticosteroids, diuretics, anti-parkinsonian agents, gastro-intestinal agents, histamine receptor antagonists, keratolyptics, lipid regulating agents, anti-anginal agents, Cox-2 inhibitors, leukotriene inhibitors, macrolides, muscle relaxants, nutritional agents, opiod analgesics, protease inhibitors, sex hormones, stimulants, muscle relaxants, anti-osteoporosis agents, anti-obesity agents, cognition enhancers, anti-urinary incontinence agents, nutritional oils, anti-benign prostate hypertrophy agents, essential fatty acids, or non-essential fatty acids.  
     
     
         81 . The method of  claim 66 , wherein the drug comprises an anti-viral agent.  
     
     
         82 . The method of  claim 81 , wherein the anti-viral agent is used to treat Hepatitis C (HepC).  
     
     
         83 . The method of  claim 82 , wherein the anti-viral agent comprises a HepC protease inhibitor.  
     
     
         84 . The method of  claim 83 , wherein the HepC protease inhibitor comprises VX-950.  
     
     
         85 . The method of  claim 66 , wherein the solvent system comprises a combination of components comprising at least one non-volatile solvent.  
     
     
         86 . The method of  claim 85 , wherein the solvent system comprises a volatile solvent and a non-volatile solvent.  
     
     
         87 . The method of  claim 86 , wherein the volatile solvent comprises methylene chloride, acetone, chloroform, or THF.  
     
     
         88 . The method of  claim 86 , wherein the non-volatile solvent comprises glacial acetic acid, DMSO, DMF, or water.  
     
     
         89 . The method of  claim 86 , wherein the non-volatile solvent is present in an amount of from about 0.1% to about 20% by wt.  
     
     
         90 . The method of  claim 86 , wherein the solvent system comprises a combination of volatile solvents with a non-volatile solvent.  
     
     
         91 . The method of  claim 90 , wherein the volatile solvents comprise methylene chloride and acetone.  
     
     
         92 . The method of  claim 91 , wherein the solvent system comprises a percent weight ratio of methylene chloride to acetone to non-volatile solvent of about 75:24:1.  
     
     
         93 . The method of  claim 90 , wherein the non-volatile solvent comprises glacial acetic acid.  
     
     
         94 . The method of  claim 90 , wherein the solvent system comprises methylene chloride, acetone, and glacial acetic acid.  
     
     
         95 . The method of  claim 94 , wherein the solvent system comprises from about 40% to about 80% methylene chloride, from about 20% to about 35% acetone, and from about 0.1% to about 15% glacial acetic acid.  
     
     
         96 . The method of  claim 90 , wherein the non-volatile solvent comprises water.  
     
     
         97 . The method of  claim 90 , wherein the solvent or combination of solvents comprises methylene chloride, acetone, and water.  
     
     
         98 . The method of  claim 97 , wherein the solvent or combination of solvents comprises from about 40% to about 80% methylene chloride, from about 20% to about 35% acetone, and from about 0.1% to about 15% water.  
     
     
         99 . The method of  claim 66 , wherein the solvent or combination of solvents comprises glacial acetic acid.  
     
     
         100 . The method of  claim 66 , wherein the solvent or combination of solvents comprises water.  
     
     
         101 . The method of  claim 66 , wherein the mixture comprises a surfactant.  
     
     
         102 . The method of  claim 101 , wherein the surfactant comprises sodium lauryl sulfate (SLS) or Vitamin E or a derivative thereof.  
     
     
         103 . A process for preparing a solid dispersion of VX-950, the process comprising: 
 a) forming or providing a solution of VX-950, a cellulosic polymer, and a solvent, wherein the solvent comprises at least one non-volatile solvent component;    b) spray-drying the mixture to form a solid amorphous dispersion comprising VX-950 and the cellulosic polymer.    
     
     
         104 . A process for preparing a solid dispersion of VX-950, the process comprising 
 a) forming or providing a mixture of VX-950, at least one cellulosic polymer, and a solvent wherein the solvent comprises glacial acetic acid; and    b) spray-drying the mixture to form a solid dispersion comprising VX-950.    
     
     
         105 . A process for preparing a solid dispersion of VX-950, the process comprising 
 a) forming or providing a mixture of VX-950, at least one cellulosic polymer, and a solvent wherein the solvent comprises water; and    b) spray-drying the mixture to form a solid dispersion comprising VX-950.    
     
     
         106 . A product made by the process of  claim 1 .  
     
     
         107 . A product made by the process of  claim 27 .  
     
     
         108 . A product made by the process of  claim 66 .  
     
     
         109 . A product made by the process of  claim 103 .  
     
     
         110 . A product made by the process of  claim 104 .  
     
     
         111 . A product made by the process of  claim 105.

Join the waitlist — get patent alerts

Track US2007218012A1 — get alerts on status changes and closely related new filings.

We store only your email — no account needed. See our privacy policy.