Solid pharmaceutical dispersions with enhanced bioavailability

• US 8,431,159 B2
• Filed: 09/07/2012
• Issued: 04/30/2013
• Est. Priority Date: 08/11/1997
• Status: Expired due to Fees

• Current Assignee: Bend Research Inc. (Lonza Group AG)
• Original Assignee: Bend Research Inc. (Lonza Group AG)
• Inventors: Curatolo, William J., Herbig, Scott M., Nightingale, James A. S.
• Primary Examiner(s): Fubara, Blessing
• Application Number:
  US13/607,452
• Publication Number:
  US 20120328679A1
• Time in Patent Office: 235 Days
• Field of Search: 424/489, 424/497, 514/419, 514/345
• US Class Current: 424/489
• CPC Class Codes: A61J 3/02 into the form of powders pulverising in general B02C
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: B01J 2/02 by dividing the liquid material into drops, e.g. by spraying, and solidifying the drops
• CPC Class Codes: B01J 8/005 Separating solid material from the gas/liquid stream separation processes per se B01D

Abstract

Spray dried solid dispersions comprising a sparingly soluble drug and hydroxypropylmethylcellulose acetate succinate (HPMCAS) provide increased aqueous solubility and/or bioavailability in a use environment.

Claims

1. A spray dried solid dispersion comprising a sparingly water-soluble drug and hydroxypropyl methylcellulose acetate succinate (HPMCAS), wherein said dispersion is a homogeneous solid solution, and said drug consists of an amorphous drug, molecularly dispersed in said dispersion, and having a drug:

polymer weight ratio between 1;

0.4 and 1;

20.

2. The spray dried solid dispersion of claim 1, wherein the dispersion further comprises one or more polymers selected from polyvinylpyrrolidone (PVP), hydroxypropyl methyl cellulose (HPMC), and hydroxypropyl cellulose (HPC).

3. The spray dried solid dispersion of claim 2, wherein the dispersion further comprises a surface acting agent.

4. The spray dried solid dispersion of claim 1, wherein the dispersion further comprises a surface acting agent.

5. The spray dried solid dispersion of claim 4, wherein said surface-active agent is selected from 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, and lecithin.

6. The spray dried solid dispersion of claim 4, wherein said surface-active agent comprises up to 25 wt % of said spray dried solid dispersion.

7. The spray dried solid dispersion of claim 1, in the form of particles less than 100 μ

m in diameter.

8. The spray dried solid dispersion of claim 1, wherein said dispersion comprises spray dried particles that are solidified in less than 2 seconds.

9. The spray dried solid dispersion of claim 1, in the form of particles having a residual solvent content less than 2 wt %.

10. The spray dried solid dispersion of claim 1, in the form of spray dried particles from a solution in which the concentration of drug in the solvent is less than 20 g/100 g and in which the total solids content is less than 25 weight %.

11. The spray dried solid dispersion of claim 1, wherein said drug has a dose to aqueous solubility ratio greater than 100.

12. The spray dried solid dispersion of claim 1, wherein said drug is crystalline when undispersed.

13. The spray dried solid dispersion of claim 1, having a drug:

polymer weight ratio between 1;

0.5 and 1;

20.

14. The spray dried solid dispersion of claim 1, having a drug:

polymer weight ratio between 1;

1 and 1;

20.

15. The spray dried solid dispersion of claim 1, wherein said spray dried solid dispersion is supersaturated in said drug.

16. spray dried solid dispersion comprising a sparingly water-soluble drug, hydroxypropyl methylcellulose acetate succinate (HPMCAS), wherein said dispersion is a homogeneous solid solution, such that said drug is molecularly dispersed and substantially completely amorphous in said dispersion, and having a drug:

polymer weight ratio between 1;

0.4 and 1;

20.