Solid pharmaceutical dispersions with enhanced bioavailability
View Patent ↗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.
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 μm 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
or a pharmaceutically acceptable salt thereof.
6. A composition as defined in claim 1 wherein said drug is
or a pharmaceutically acceptable salt thereof.
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
or a pharmaceutically acceptable salt thereof.
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
or a pharmaceutically acceptable salt thereof.
11. A composition as defined in claim 1 wherein said drug is
or a pharmaceutically acceptable salt thereof.
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.