Long acting injectable formulations

A non-aqueous long acting injectable formulation comprising:

• (i) about 5% to about 20% by weight of lurasidone as free base or salt;
• (ii) about 80% to about 95% by weight of a non-aqueous liquid vehicle comprising a hydrophobic lipid comprising a glyceryl ester of a C6-C24 fatty acid;
• and
• (iii) about 0.5% to about 10% by weight of an amphiphilic agent selected from the group consisting of ethanol, benzyl alcohol, benzyl benzoate, N-methyl-2-pyrrolidone, dimethylacetamide, sorbitan esters, polyethoxylated sorbitan esters, fatty alcohol ethoxylates, fatty acid ethoxylates, polyoxyethylene polyoxypropylene block copolymers, and combinations thereof,
• wherein the lurasidone is dispersed as discrete particles having a D90 particle size of about 0.5 μm to about 25 μm in the formulation, and wherein the formulation is non-gelling and thixotropic with a viscosity of less than 10 poise at a shear rate of 10/s at 25° C. and a viscosity of greater than 15 poise at a shear rate of less than or equal to about 0.1/s at 25° C., wherein administration of said dosage form to a subject increases the ratio of AUC/Cmax by at least 5-times that of immediate release dosage form, and wherein in vivo release of the lurasidone is extended over a period of greater than about 1 week.

A non-aqueous long acting injectable formulation comprising:

• (iv) about 5% to about 20% by weight of lurasidone as free base or salt;
• (v) about 80% to about 95% by weight of a non-aqueous liquid vehicle comprising a hydrophobic lipid comprising a glyceryl ester of a C6-C24 fatty acid;
• and
• (vi) about 0.5% to about 10% by weight of an amphiphilic agent selected from the group consisting of ethanol, benzyl alcohol, benzyl benzoate, N-methyl-2-pyrrolidone, dimethylacetamide, sorbitan esters, polyethoxylated sorbitan esters, fatty alcohol ethoxylates, fatty acid ethoxylates, polyoxyethylene polyoxypropylene block copolymers, and combinations thereof,
• wherein the lurasidone is dispersed as discrete particles having a D90 particle size of about 0.5 μm to about 25 μm in the formulation, and wherein administration of said dosage form to a subject increases the half-life by at least 5-times that of immediate release dosage form, and wherein in vivo release of the lurasidone active is extended over a period of greater than about 1 week.

A non-aqueous long acting injectable formulation comprising:

• (vii) about 5% to about 20% by weight of lurasidone as free base or salt;
• (viii) about 80% to about 95% by weight of a non-aqueous liquid vehicle comprising a hydrophobic lipid comprising a glyceryl ester of a C6-C24 fatty acid;
• and
• (ix) about 0.1% 0.5% to about 10% by weight of an amphiphilic agent selected from the group consisting of ethanol, benzyl alcohol, benzyl benzoate, N-methyl-2-pyrrolidone, dimethylacetamide, sorbitan esters, polyethoxylated sorbitan esters, fatty alcohol ethoxylates, fatty acid ethoxylates, polyoxyethylene polyoxypropylene block copolymers, and combinations thereof,
• wherein the lurasidone is dispersed as discrete particles having a D90 particle size of about 0.5 μm to about 25 μm in the formulation, and wherein the formulation is non-aqueous, non-gelling and thixotropic with a viscosity of less than 10 poise at a shear rate of 10/s at 25° C. and a viscosity of greater than 15 poise at a shear rate of less than or equal to about 0.1/s at 25° C., wherein administration of said dosage form to a subject increases the MRT by at least 5-times that of immediate release dosage form, and wherein in vivo release of the lurasidone is extended over a period of greater than about 1 week.