Pharmaceutical compositions providing enhanced drug concentrations

• US 8,026,286 B2
• Filed: 12/20/2000
• Issued: 09/27/2011
• Est. Priority Date: 12/23/1999
• Status: Expired due to Fees

• Current Assignee: Bend Research Inc. (Lonza Group AG)
• Original Assignee: Bend Research Inc. (Lonza Group AG)
• Inventors: Nightingale, James A. S., Babcock, Walter C., Friesen, Dwayne T., Lorenz, Douglas A., Shanker, Ravi M., Curatolo, William J.
• Primary Examiner(s): FUBARA, BLESSING M
• Application Number:
  US09/742,785
• Publication Number:
  US 20020006443A1
• Time in Patent Office: 3,933 Days
• Field of Search: 514/772.4, 424/489, 424/486, 424/493, 424/468
• US Class Current: 514/772.4
• 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 a crystalline highly soluble salt form other than the crystalline hydrochloride salt; and

(b) a concentration-enhancing polymer selected from the group consisting of cellulose acetate phthalate, cellulose acetate trimellitate, hydroxypropyl methyl cellulose phthalate, and hydroxypropyl methyl cellulose acetate succinate

wherein

said drug alone has an aqueous solubility of up to about 1 to 2 mg/mL; and

said composition is not a dispersion and said drug and said polymer are present as particles in a dry physical mixture.

2. 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.

3. The composition of claim 1, wherein said drug is ziprasidone.

5. The composition of claim 1 or 4 wherein said crystalline highly soluble salt form is selected from the group consisting of the bromide, acetate, iodide, mesylate, phosphate, maleate, citrate, sulfate, tartrate, and lactate salts.

6. The composition of claim 1 or 4 wherein said crystalline highly soluble salt form is selected from the group consisting of the sodium, calcium, potassium, zinc, magnesium, lithium, aluminum, meglumine, diethanolamine, benzathine, choline, and procaine salts.

7. The composition of claim 1 or 4 wherein said drug alone has an aqueous solubility of less than 0.01 mg/mL at pH 1 to 8.

8. The composition of claim 1 or 4 wherein said drug and said polymer are combined without the use of a solvent.

4. A composition comprising:

(a) a drug in a crystalline highly soluble salt form other than the crystalline hydrochloride salt; and

(b) hydroxypropyl methyl cellulose acetate succinate

wherein

said composition is not a dispersion;

said drug alone has an aqueous solubility up to about 1 to 2 mg/mL; and

said crystalline highly soluble salt form and said hyroxypropylmethyl cellulose acetate succinate are present as particles in a dry physical mixture.