Pharmaceutical solid dispersions

• US 8,481,081 B2
• Filed: 06/10/2003
• Issued: 07/09/2013
• 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:
  US10/459,808
• Publication Number:
  US 20040013734A1
• Time in Patent Office: 3,682 Days
• Field of Search: 424/484
• US Class Current: 424/488
• 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. At least a major portion of the drug in the dispersion is amorphous. The polymer has a glass transition temperature of at least 100° C. measured at a relative humidity of fifty percent. Another aspect of the invention comprises the same composition except that the dispersion has a glass transition temperature of at least 50° C. at a relative humidity of fifty percent. 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 dispersion consisting of a low-solubility drug and cellulose acetate phthalate, wherein said dispersion is formed by spray drying with a non-aqueous solvent in which said drug and said cellulose acetate phthalate are both soluble, and wherein at least 90% of said drug once dispersed in said dispersion is amorphous, said dispersion has a single glass transition temperature of at least 50°

C. measured at 50% relative humidity, said composition provides a maximum concentration of said drug in a use environment that is at least 1.5-fold that of a control comprising an equivalent quantity of undispersed drug.

2. The dispersion of claim 1 wherein said low-solubility drug is selected from the group consisting of antihypertensives, antianxiety agents, anticlotting agents, anticonvulsants, blood glucose-lowering agents, decongestants, antihistamines, antitussives, antineoplastics, beta blockers, anti-inflammatories, antipsychotic agents, cognitive enhancers, cholesterol-reducing agents, antiobesity agents, autoimmune disorder agents, anti-impotence agents, antibacterial and antifungal agents, hypnotic agents, anti-Parkinsonism agents, anti-Alzheimer'"'"'s disease agents, antibiotics, anti-depressants, and antiviral agents.

3. A composition comprising:

(a) the solid dispersion of claim 1 or 2; and

(b) a concentration enhancing polymer selected from the group consisting of hydroxypropyl methyl cellulose acetate succinate, hydroxypropyl methyl cellulose acetate phthalate, hydroxypropyl methyl cellulose acetate, hydroxypropyl methyl cellulose succinate, hydroxypropyl methyl cellulose phthalate, hydroxypropylmethyl cellulose, hydroxypropyl cellulose, methyl cellulose, hydroxyethyl cellulose, hydroxyethyl methyl cellulose, hydroxy ethyl cellulose acetate, hydroxyethyl ethyl cellulose, hydroxy ethyl methyl cellulose acetate succinate, hydroxyethyl methyl cellulose acetate phthalate, carboxymethyl cellulose, carboxyethyl cellulose, polyvinyl alcohol, polyvinyl alcohol polyvinyl acetate copolymers, polyethylene glycol, polyethylene glycol polypropylene glycol copolymers, polyvinyl pyrrolidone, polyethylene polyvinyl alcohol copolymers, carboxylic acid-functionalized polymethacrylates, amine-functionalized polymethacrylates, chitosan, and chitin.