Pharmaceutical solid dispersions

• US 8,828,442 B2
• Filed: 09/11/2012
• Issued: 09/09/2014
• Est. Priority Date: 02/10/1999
• Status: Expired due to Fees

• Current Assignee: Bend Research Inc. (Lonza Group AG)
• Original Assignee: Bend Research Inc. (Lonza Group AG)
• Inventors: Babcock, Walter C., Friesen, Dwayne T., Nightingale, James A. S., Shanker, Ravi M.
• Primary Examiner(s): Vu, Jake
• Application Number:
  US13/610,350
• Publication Number:
  US 20130029965A1
• Time in Patent Office: 728 Days
• Field of Search: 424/489
• US Class Current: 424/489
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/12 Antihypertensives

Abstract

A composition comprises a solid dispersion comprising a low-solubility drug and at least one polymer. In another aspect of the invention, a composition comprises a solid dispersion comprising a low-solubility drug and a stabilizing polymer. At least a major portion of the drug in the dispersion is amorphous. The composition also includes a concentration-enhancing polymer that increases the concentration of the drug in a use environment. The stabilizing polymer has a glass transition temperature that is greater than the glass transition temperature of the concentration-enhancing polymer at a relative humidity of 50%.

Claims

1. A composition, comprising:

(a) a spray-dried solid dispersion comprising a low-solubility drug, a concentration-enhancing polymer and a stabilizing polymer selected from the group consisting of cellulose acetate phthalate, methyl cellulose acetate phthalate, hydroxypropyl methyl cellulose acetate phthalate, cellulose acetate trimellitate, methyl cellulose acetate trimellitate, hydroxypropyl methyl cellulose acetate trimellitate, wherein the amount of drug in crystalline form, once dispersed in said solid dispersion, does not exceed 20%; and

(b) wherein said concentration-enhancing polymer is selected from the group consisting of hydroxypropyl methyl cellulose acetate succinate, hydroxypropyl methyl cellulose acetate, hydroxypropyl methyl cellulose succinate, hydroxypropyl methyl cellulose phthalate, hydroxypropylcellulose, methyl cellulose, hydroxyethyl cellulose, hydroxy ethyl cellulose acetate, hydroxyethyl ethyl cellulose, hydroxy ethyl methyl cellulose acetate succinate, hydroxyethyl methyl cellulose acetate phthalate, polyvinyl alcohol/polyvinyl acetate copolymers, polyethylene glycol, polyethylene glycol polypropylene glycol copolymers, polyvinyl pyrrolidone, polyethylene polyvinyl alcohol copolymers, carboxylic acid-functionalized polymethacrylates, and amine-functionalized polymethacrylates, and increases the maximum drug concentration in a use environment relative to a control composition comprising an equivalent quantity of undispersed drug wherein, when measured at 50% relative humidity, the glass-transition temperature (Tg) of said stabilizing polymer is greater than the Tg of said concentration-enhancing polymer, and wherein said drug, said stabilizing polymer, and said concentration-enhancing polymer are codispersed in said dispersion.

2. The composition of claim 1 wherein the Tg of said stabilizing polymer is at least 10°

C. greater than the Tg of said concentration-enhancing polymer.

3. The composition of claim 1 wherein the Tg of said stabilizing polymer is at least 20°

C. greater than the Tg of said concentration-enhancing polymer.

4. The composition of claim 1 wherein said drug and said stabilizing polymer are soluble in a common solvent.

5. The composition of claim 1 wherein said maximum drug concentration in a use environment is enhanced at least 1.5-fold that of said control composition.

6. The composition of claim 1 wherein said dispersion is substantially homogeneous.

7. The composition of claim 1 wherein said concentration-enhancing polymer provides a maximum drug concentration in a use environment that is least 1.5-fold that of a control comprising an equivalent quantity of said drug dispersed in an equivalent quantity of said stabilizing polymer.

8. The composition of claim 1 wherein the amount of said drug in crystalline form, once dispersed in said dispersion, does not exceed 10%.