Pharmaceutical compositions of posaconazole

A delayed-release pharmaceutical composition prepared by hot-melt extrusion comprising:

• a. an extrudate comprising posaconazole or a pharmaceutically acceptable salt thereof, a first enteric polymer and a first non-enteric polymer;
• and
• b. an extra-granular fraction comprising a blend of a second enteric polymer and a second non-enteric polymer,
• wherein the first enteric polymer and second enteric polymer are each independently selected from the group consisting of hydroxypropylmethyl cellulose acetate succinate, hydroxypropylmethyl cellulose phthalate, polyvinylacetate phthalate and mixtures thereof;
• wherein the first non-enteric polymer and second non-enteric polymer are each independently selected from the group consisting of polyvinylpyrrolidone, polyethylene glycol, hydroxypropylmethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, and mixtures thereof;
• and
• wherein the pharmaceutical composition may be administered to a patient without regard to food.

A process for preparing a solid oral dosage form, comprising:

• a. dry-blending posaconazole, hydroxypropylmethyl cellulose acetate succinate (HPMC-AS) and hydroxypropyl cellulose (HPC) to form a mixture,
• b. heating the mixture to a temperature above the glass transition temperature (Tg) of the hydroxypropylmethyl cellulose acetate succinate (HPMC-AS) and the hydroxypropyl cellulose (HPC), thereby forming a molten dispersion of the posaconazole in hydroxypropylmethyl cellulose acetate succinate (HPMC-AS) and hydroxypropyl cellulose (HPC);
• and
• c. cooling the dispersion formed in (b) to provide a composition of posaconazole in hydroxypropylmethyl cellulose acetate succinate (HPMC-AS) and hydroxypropyl cellulose (HPC),
• d. milling the composition from (c) to provide granules comprising posaconazole;
• and
• e. mixing the granules from (d) with an extra-granular mixture comprising an enteric polymer and a non-enteric polymer to form a blend,
• wherein the enteric polymer is selected from the group consisting of hydroxypropylmethyl cellulose acetate succinate, hydroxypropylmethyl cellulose phthalate, polyvinylacetate phthalate and mixtures thereof;
• and
• wherein the non-enteric polymer is selected from the group consisting of polyvinylpyrrolidone, polyethylene glycol, hydroxypropylmethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose and mixtures thereof.