Solid pharmaceutical dispersions with enhanced bioavailability

• US 8,263,128 B2
• Filed: 01/26/2001
• Issued: 09/11/2012
• 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 M
• Application Number:
  US09/770,562
• Publication Number:
  US 20020009494A1
• Time in Patent Office: 4,246 Days
• Field of Search: 424/489, 424/499, 424/497, 514/419, 514/345, 514/595
• 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 biavailability in a use environment.

Claims

1. A spray dried solid dispersion consisting of a sparingly water-soluble drug and hydroxypropyl methylcellulose acetate succinate (HPMCAS), said drug being molecularly dispersed and amorphous in said dispersion, having a drug:

polymer weight ratio between 1;

0.4 and 1;

20, and said dispersion is a homogeneous solid solution of said drug in said HPMCAS.

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

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

m in diameter.

4. A composition as defined in claim 1 wherein said drug is a glycogen phosphorylase inhibitor.

5. A composition as defined in claim 1 wherein said drug is

6. A composition as defined in claim 1 wherein said drug is

7. A composition as defined in claim 1 wherein said drug is a 5-lipoxygenase inhibitor.

8. A composition as defined in claim 1 wherein said drug is

9. A composition defined in claim 1 wherein said drug is a corticotropic releasing hormone (CRH) inhibitor.

10. A composition as defined in claim 1 wherein said drug is

11. A composition as defined in claim 1 wherein said drug is

12. The spray dried solid dispersion of claim 1, wherein said drug is an antipsychotic.

13. The spray dried solid dispersion of claim 1, wherein said drug is ziprasidone.

14. A composition as defined in claim 1 wherein said drug is selected from griseofulvin, nifedipine, and phenytoin.

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

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

17. 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 %.

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

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

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

polymer weight ratio between 1;

0.5 and 1;

20.

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

polymer weight ratio between 1;

1 and 1;

20.

22. The spray dried solid dispersion of claim 1, wherein said drug is selected from the group consisting of glycogen phosphorylase inhibitors, 5-lipoxygenase inhibitors, corticotropic releasing hormone inhibitors, griseofulvin, nifedipine, and phenytoin.

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