Pharmaceutical compositions providing enhanced drug concentrations

• US 8,980,321 B2
• Filed: 07/14/2014
• Issued: 03/17/2015
• Est. Priority Date: 12/23/1999
• Status: Active Grant

• Current Assignee: Bend Research Inc. (Lonza Group AG)
• Original Assignee: Bend Research Inc. (Lonza Group AG)
• Inventors: Curatolo, William J., Shanker, Ravi M., Babcock, Walter C., Friesen, Dwayne T., Nightingale, James A. S., Lorenz, Douglas A.
• Primary Examiner(s): Fubara, Blessing M
• Application Number:
  US14/331,172
• Publication Number:
  US 20140322325A1
• Time in Patent Office: 246 Days
• Field of Search: 424/400, 424/465, 424/490, 424/468, 424/497, 424/451, 424/456, 424/484, 424/480, 514/570, 514/569, 514/338, 514/165, 514/422, 514/161, 514/162, 514/304, 514/305, 514/534, 514/629, 514/781, 514/657, 514/425, 514/397, 514/266.4, 514/254.04
• US Class Current: 424/480
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/404 Indoles, e.g. pindolol
• CPC Class Codes: A61K 31/4178 not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
• CPC Class Codes: A61K 31/4375 the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/517 ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61K 9/1629 Organic macromolecular compounds
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61P 11/14 Antitussive agents
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• 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 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• 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 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• 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 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/12 : Antihypertensives

Abstract

A drug in a solubility-improved form is combined with a concentration-enhancing polymer in a sufficient amount so that the combination provides substantially enhanced drug concentration in a use environment relative to a control comprising the same amount of the same solubility-improved form of drug without the concentration-enhancing polymer.

Claims

1. A composition comprising:

(a) a drug in a pharmaceutically acceptable solubility-improved form that is an amorphous form of the drug; and

(b) a concentration-enhancing polymer selected from the group consisting of cellulose acetate phthalate, cellulose acetate trimellitate, hydroxypropyl methyl cellulose phthalate, hydroxypropyl methyl cellulose acetate succinate, hydroxypropyl methyl cellulose acetate, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, methyl cellulose, hydroxyethyl methyl cellulose, hydroxyethyl cellulose acetate, hydroxyethyl ethyl cellulose, carboxymethyl ethyl cellulose, acrylate and methacrylate copolymers, vinyl polymers and copolymers having substituents of hydroxyl, alkylacyloxy, and cyclicamido, and mixtures thereof,

wherein said drug alone has an aqueous solubility of up to 2 mg/mL at pH 1 to 8, and said composition is not a molecular dispersion.

2. The composition of claim 1 wherein said drug alone has an aqueous solubility of less than 0.01 mg/mL at pH 1 to 8.

3. The composition of claim 1 further comprising one or more surfactants selected from tocopheroyl TPGS, fatty acid and alkyl sulfonates, benzethanium chloride, docusate sodium, polyoxyethylene sorbitan fatty acid esters, sodium taurocholic acid, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, lecithin, phospholipids, mono- and diglycerides, and combinations thereof.

4. The composition of claim 1 wherein said drug is selected from 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.

5. The composition of claim 1 wherein said composition is formulated into tablets, capsules, suspensions, powders for suspension, creams, transdermal patches, or depots.

6. The composition of claim 5 wherein said composition is formulated into a layered tablet wherein one or more layers comprise the drug and one or more other layers comprise the concentration-enhancing polymer.

7. The composition of claim 5 wherein said composition is formulated into a coated tablet wherein the tablet core comprises the drug and the coating comprises the concentration-enhancing polymer.

8. The composition of claim 5 wherein said composition is formulated into a capsule.

9. The composition of claim 1 comprising a physical mixture of the drug and the concentration-enhancing polymer.

10. The composition of claim 1 wherein the drug and concentration-enhancing polymer are present in a drug-to-polymer weight ratio of 0.01 to 5.