Solid pharmaceutical dispersions with enhanced bioavailability
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.
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 μm 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.