Pharmaceutical compositions of amorphous dispersions of drugs and lipophilic microphase-forming materials

• US 10,357,455 B2
• Filed: 07/27/2018
• Issued: 07/23/2019
• Est. Priority Date: 02/01/2002
• Status: Expired due to Term

• Current Assignee: Lonza Bend Incorporated (Lonza Group AG)
• Original Assignee: Bend Research Inc. (Lonza Group AG)
• Inventors: Perlman, Michael E., Shanker, Ravi M., Babcock, Walter C., Friesen, Dwayne Thomas, Rabenstein, Mark D., Smithey, Daniel Tod
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): Al-Awadi, Danah
• Application Number:
  US16/047,965
• Publication Number:
  US 20180338915A1
• Time in Patent Office: 361 Days
• Field of Search: None
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/4706 4-Aminoquinolines; 8-Aminoquinolines, e.g. chloroquine, primaquine
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• CPC Class Codes: A61K 9/145 with organic compounds
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds

Abstract

A pharmaceutical composition comprises a solid amorphous dispersion comprising a low-solubility drug and a concentration-enhancing polymer and a lipophilic microphase-forming material. Alternatively, a solid amorphous dispersion comprising a low-solubility drug and a concentration-enhancing polymer is co-administered with a lipophilic microphase-forming material to an in vivo use environment.

Claims

1. A composition in the form of a dosage form, comprising:

a) a solid amorphous dispersion comprising an active pharmaceutical ingredient and a polymer; and

b) an amphiphilic material adsorbed onto a water insoluble solid excipient;

wherein the amphiphilic material is a sulfonated hydrocarbon or salt thereof, a poloxamer, a polyoxyethylene alkyl ether, a polyoxyethylene sorbitan fatty acid ester, a short-chain glyceryl mono-alkylate, a polyglycolized glyceride, a mono- and di-alkylate ester of a polyol, polyoxyethylene (40 or

     60) hydrogenated castor oil, polyoxyethylene (35) castor oil, alpha tocopheryl polyethylene glycol 1000 succinate, glyceryl PEG 8 caprylate/caprate, PEG 32 glyceryl laurate, a polyoxyethylene fatty acid ester, or a polyoxyethylene fatty acid ether; and

wherein the water insoluble solid excipient is microcrystalline cellulose, silica, dibasic calcium phosphate, calcium silicate, clays, hydrated aluminum silicate, bentonite, hectorite, Na-, Al-, and Fe-montmorillonite, silicon dioxide, magnesium trisilicate, aluminum hydroxide, magnesium hydroxide, magnesium oxide, or talc; and

wherein the solid amorphous dispersion is in the form of solid amorphous dispersion particles and the water insoluble solid excipient, together with the amphiphilic material adsorbed onto the water insoluble excipient, is in the form of particles distinct from the solid amorphous dispersion particles.

2. The composition of claim 1, wherein the amphiphilic material is alpha tocopheryl polyethylene glycol 1000 succinate.

3. The composition of claim 1, wherein the amphiphilic material is a poloxamer.

4. The composition of claim 1, wherein the amphiphilic material is a polyoxyethylene sorbitan fatty acid ester.

5. The composition of claim 1, wherein the amphiphilic material is polyoxyethylene 20 sorbitan monolaurate or polyoxyethylene 80 sorbitan monooleate.

6. The composition of claim 1, wherein the amphiphilic material is polyoxyethylene (40 or 60) hydrogenated castor oil or polyoxyethylene (35) castor oil.

7. The composition of claim 1, wherein the amphiphilic material is a polyoxyethylene fatty acid ester or a polyoxyethylene fatty acid ether.

8. The composition of claim 1, wherein the amphiphilic material is a polyglycolized glyceride.

9. The composition of claim 1, wherein the amphiphilic material is a sulfonated hydrocarbon or a salt thereof.

10. The composition of claim 1, wherein the amphiphilic material is sodium lauryl sulfate.

11. The composition of claim 1, wherein the amphiphilic material is a polyethoxylated castor oil.

12. The composition of claim 1, wherein the amphiphilic material is a liquid at a temperature of about 50°

C. or less.