Claims for Patent: 8,852,632

Summary for Patent: 8,852,632

Title:	Pharmaceutical formulation containing a release rate controlling composition
Abstract:	Pharmaceutical formulations suitable for oral administration in solid dosage forms are described. The compositions comprise an effective amount of a base salt of a compound of Formula (I) and a release rate controlling composition comprising a solubilizing agent, a gelling agent, and a water soluble filler; wherein R, R, Rand Rare defined herein. The formulations are suitable for use in the inhibition of HIV integrase, the treatment and prophylaxis of HIV infection, and the treatment, prophylaxis and delay in the onset of AIDS.
Inventor(s):	Pourkavoos Nazaneen, Ney James R., Cruanes Maria T., Wu Yunhui, Palkar Saurabh A.
Assignee:	Merck Sharp & Dohme Corp.
Application Number:	US11792118
Patent Claims:	2. The formulation according to claim 1 , wherein the potassium salt of Compound A is the form 1 crystalline potassium salt of Compound A.3. The formulation according to claim 1 , wherein the poloxamer is poloxamer 407 milled to an average particle size in a range of from about 50 to about 150 microns; the high-viscosity hydroxypropylmethylcellulose is that produces a 2 wt. % aqueous solution having a viscosity of at least about 2900 centipoise (cps) at 20° C.; and the lactose is lactose hydrous spray dried.4. The formulation according to claim 3 , wherein the potassium salt of Compound A is Form 1 crystalline potassium salt of Compound A.5. The formulation according to claim 1 , which further comprises a diluent and a lubricant claim 1 , wherein the diluent comprises microcrystalline cellulose and optionally calcium phosphate; and the lubricant comprises a metal stearate and a metal stearyl fumarate.6. The formulation according to claim 5 , wherein:the potassium salt of Compound A is employed in an amount in a range of from about 40 to about 60 wt. % on a free phenol basis;the microcrystalline cellulose is employed in an amount in a range of from about 5 to about 30 wt. %;the calcium phosphate is employed in an amount in a range of from about zero to about 15 wt. %; andthe metal stearate and metal stearyl fumarate are each independently employed in an amount in a range of from about 1 to about 3 wt. %.7. The formulation according to claim 6 , wherein the potassium salt of Compound A is Form 1 crystalline potassium salt of Compound A; the poloxamer is poloxamer 407 milled to an average particle size in a range of from about 50 to 150 microns; the high-viscosity hydroxypropylmethylcellulose is HPMC having a viscosity of about 4000 mPa·sec that produces a 2 wt. % aqueous solution having a viscosity of at least about 2900 centipoise (cps) at 20° C.; the lactose is lactose hydrous spray dried; the microcrystalline cellulose has a nominal particle size of 100 μm claim 6 , a bulk density of 0.28 to 0.33 g/cc and a moisture content of 3% to 5%; the calcium phosphate is dibasic calcium phosphate; the metal stearate is magnesium stearate; and the metal stearyl fumarate is sodium stearyl fumarate.8. The formulation according to claim 1 , wherein the potassium salt of Compound A is employed on a free phenol basis in an amount in a range of from about 100 mg to about 600 mg.9. The formulation according to claim 8 , wherein the formulation is encapsulated or compressed into a tablet.10. The formulation according to claim 2 , wherein the potassium salt of Compound A is employed on a free phenol basis in an amount in a range of from about 100 mg to about 600 mg.11. A process for preparing a compressed tablet of a pharmaceutical formulation according to claim 5 , wherein the method comprises:(A) blending a mixture of the Compound A K salt, the solubilizing agent comprising the poloxamer, the gelling agent comprising the high-viscosity hydroxypropylmethylcellulose, the water-soluble filler comprising the lactose, the first diluent comprising the microcrystalline cellulose and calcium phosphate, a first portion of the first lubricant comprising part of the metal stearate and the metal stearyl fumarate;(B) sieving the blended mixture, and then further blending the sieved mixture;(C) rolling the sieved and blended mixture to form a compact, and then sizing the resulting compact to form granules;(D) blending the granules with the remaining portion of the lubricant comprising the rest of the metal stearate; and(E) compressing the lubricated granules of Step D to obtain the tablet.12. The process according to claim 11 , wherein:the potassium salt of Compound A is employed in an amount in a range of from about 40 to about 60 wt. % on a free phenol basis;the poloxamer is employed in an amount in a range of from about 10 to about 20 wt. %;the high-viscosity hydroxypropylmethylcellulose is employed in an amount in a range of from about 3 to about 9 wt. %;the lactose is employed in an amount in a range of from 3 to about 9 wt. %;the microcrystalline cellulose and calcium phosphate are each independently employed in an amount in a range of from about 5 to about 25 wt. %; andthe metal stearate and metal stearyl fumarate are each independently employed in an amount in a range of from about 1 to about 3 wt. %.13. The process according to claim 12 , wherein the poloxamer is poloxamer 407 milled to an average particle size in a range of from about 50 to 150 microns; the high-viscosity hydroxypropylmethylcellulose having a viscosity of about 4000 mPa·sec that produces a 2 wt. % aqueous solution having a viscosity of at least 2900 centipoise at 20° C.; the lactose is lactose hydrous spray dried; the microcrystalline cellulose has a nominal particle size of 100 μm claim 12 , a bulk density of 0.28 to 0.33 g/cc and a moisture content of 3% to 5%; the calcium phosphate is dibasic calcium phosphate; the metal stearate is magnesium stearate; and the metal stearyl fumarate is sodium stearyl fumarate.14. The process according to claim 13 , wherein the potassium salt of Compound A is Form 1 crystalline potassium salt of Compound A.15. The process according to claim 12 , wherein the process further comprises: (F) coating the compressed tablet with Opadry II HP to afford a coated tablet in which the coating is from about 2 to about 4% of the weight of the compressed tablet.16. A method for the treatment of HIV infection in a subject in need thereof which comprises administering to the subject the pharmaceutical formulation according to .