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 process for making a solid dispersion consisting of a sparingly water-soluble drug, hydroxypropyl methyl cellulose acetate succinate (HPMCAS), and a surface-active agent, said drug being molecularly dispersed and amorphous in said dispersion, said process consisting essentially of the steps of:
(a) providing a solution consisting of a sparingly water-soluble drug, HPMCAS, a surface-active agent, and a solvent or a solvent and water mixture, said solvent being a compound in which said drug, said surface-active agent, and HPMCAS are mutually soluble, said solution having a ratio of said drug to HPMCAS of from 1 to 0.4 to 1 to 20;
(b) breaking up said solution into small droplets, wherein said droplets range in size from 1 to 500 μm;
(c) directing said droplets and a drying gas into a drying chamber to cause evaporation of a sufficient amount of said solvent from said droplets to cause solidification of said droplets in less than 5 seconds to form said solid dispersion.
2. The process of claim 1 , 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.
3. The process of claim 1 , wherein said surface-active agent comprises up to 25 wt% of said solid dispersion.
4. A process for making a solid dispersion consisting of a sparingly water-soluble drug and hydroxypropyl methyl cellulose acetate succinate (HPMCAS), said drug being molecularly dispersed and amorphous in said dispersion, said process consisting essentially of the steps of:
(a) providing a solution consisting of a sparingly water-soluble drug, HPMCAS, and a solvent or a solvent and water mixture, said solvent being a compound in which said drug and said HPMCAS are mutually soluble, said solution having a ratio of said drug to HPMCAS of from 1 to 0.4 to 1 to 20;
(b) breaking up said solution into small droplets, wherein said droplets range in size from 1 to 500 μm;
(c) directing said droplets and a drying gas into a drying chamber to cause evaporation of a sufficient amount of said solvent from said droplets to cause solidification of said droplets in less than 5 seconds to form particles of said solid dispersion.
5. The process of claim 1 or 4 , wherein said solvent is a mixture of compounds.
6. The process of claim 5 wherein said solvent is selected from one or more of methanol, ethanol, n-propanol, iso-propanol, butanol, acetone, methyl ethyl ketone, methyl iso-butyl ketone, ethyl acetate, propylacetate, acetonitrile, methylene chloride, toluene, 1,1,1-trichloroethane, dimethylacetamide, dimethylsulfoxide, and water.
7. The process of claim 1 or 4 , wherein said solvent has a boiling point of less than 150° C.
8. The process of claim 1 or 4 , wherein HPMCAS is present in an amount in said solution that constitutes at least 50 wt% of said solid dispersion.
9. The process of claim 1 or 4 , wherein said solidification occurs in less than 2 seconds.
10. The process of claim 1 or 4 , wherein said drying gas is heated.
11. The process of claim 1 or 4 , wherein the concentration of drug in said solvent is less than 20 g/100 g of said solvent.
12. A process for making a solid dispersion comprising a sparingly water-soluble drug, hydroxypropyl methyl cellulose acetate succinate (HPMCAS), and a surface-active agent, said drug being molecularly dispersed and substantially completely amorphous in said dispersion, said process consisting essentially of the steps of:
(a) providing a solution comprising a sparingly water-soluble drug, HPMCAS, a surface-active agent, and a solvent, said solvent being a compound in which said drug, said surface-active agent, and HPMCAS are mutually soluble, said solution having a ratio of said drug to HPMCAS of from 1 to 0.4 to 1 to 20;
(b) breaking up said solution into small droplets, wherein said droplets range in size from 1 to 500 μm;
(c) directing said droplets and a drying gas into a drying chamber to cause evaporation of a sufficient amount of said solvent from said droplets to cause solidification of said droplets in less than 5 seconds to form said solid dispersion.