Claims for Patent: 8,771,733

Summary for Patent: 8,771,733

Title:	Pharmaceutical composition containing an anti-nucleating agent
Abstract:	Pharmaceutical compositions suitable for oral administration in solid dosage forms are described. The compositions comprise an effective amount of a drug compound in the form of a salt, wherein the drug salt is characterized by conversion to a less soluble form of the drug compound under certain pH conditions, and an anti-nucleating agent.
Inventor(s):	Cruanes Maria T., Xu Wei, Artino Laura M., Zhu Honggang
Assignee:	Merck Sharp & Dohme Corp.
Application Number:	US11792190
Patent Claims:	2. The pharmaceutical composition according to claim 1 , wherein the potassium salt of Compound A is Form 1 potassium salt of Compound A.3. The pharmaceutical composition according to claim 1 , wherein the anti-nucleating agent comprises hydroxypropylmethylcellulose.4. The pharmaceutical composition according to claim 1 , which further comprises a first diluent claim 1 , a second diluent claim 1 , a disintegrant claim 1 , and a lubricant.5. The pharmaceutical composition according to claim 4 , wherein:the anti-nucleating agent is hydroxypropylmethylcellulose;the first diluent is microcrystalline cellulose;the second diluent is lactose or dibasic calcium phosphate;the disintegrant is croscarmellose sodium; andthe lubricant is magnesium stearate.6. The pharmaceutical composition according to claim 5 , wherein:the microcrystalline cellulose is employed in an amount of from 10 to 85 wt. %;the lactose or dibasic calcium phosphate is employed in an amount of from 10 to 85 wt. %;the croscarmellose sodium is employed in an amount of from 1 to 10 wt. %; andthe magnesium stearate is employed in an amount of from 0.5 to 10 wt. %.7. The pharmaceutical composition according to claim 6 , wherein the potassium salt of Compound A is Form 1 potassium salt of Compound A.8. The pharmaceutical composition according to claim 6 , wherein the composition is encapsulated or compressed into a tablet.9. The pharmaceutical composition according to claim 8 , wherein the potassium salt of Compound A is employed in an amount of from 5 mg to 900 mg.10. A process for preparing a compressed tablet having a pharmaceutical composition according to claim 4 , wherein the method comprises:(A) blending a mixture of the Compound A potassium salt, the anti-nucleating agent, none or all or a first portion of the first diluent, the second diluent, the disintegrant, and a first portion of the lubricant;(B) either (i) compressing the blended mixture to form one or more slugs or (ii) rolling the blended mixture to form a compact, and then sizing the resulting one or more slugs or the resulting compact to form granules;(C) blending the granules with all or none or the remaining portion of the first diluent and the remaining portion of the lubricant; and(D) compressing the lubricated granules of Step C to obtain the tablet.11. The process according to claim 10 , wherein:the anti-nucleating agent is hydroxypropylmethylcellulose;the first diluent is microcrystalline cellulose;the second diluent is lactose or dibasic calcium phosphate;the disintegrant is croscarmellose sodium; andthe lubricant is magnesium stearate.12. The process according to claim 11 , wherein:the microcrystalline cellulose is employed in an amount of from 10 to 85 wt. %;the lactose or dibasic calcium phosphate is employed in an amount of from 10 to 85 wt. %;the croscarmellose sodium is employed in an amount of from 1 to 10 wt. %; andthe magnesium stearate is employed in an amount of from 0.5 to 10 wt. %.13. A process for preparing a compressed tablet having a pharmaceutical composition according to claim 4 , wherein the method comprises:(A) wet granulating a mixture of Compound A potassium salt, the anti-nucleating agent, the first diluent, the second diluent, and the disintegrant, and then optionally milling the wet granulated mixture;(B) drying the wet granulated mixture of Step A;(C) milling the dried mixture of Step B;(D) lubricating the milled mixture of Step C with the lubricant; and(E) compressing the lubricated mixture of Step D into a tablet.14. A method for improving the pharmacokinetics of a compound of Formula I as recited in orally administered in the form of a base salt claim 1 , wherein the method comprises administering the compound base salt as a component in a solid-dosage pharmaceutical composition that includes an anti-nucleating agent.15. A method for the treatment of HIV infection in a subject in need thereof which comprises administering to the subject the pharmaceutical composition according to .16. The pharmaceutical composition according to claim 6 , wherein:the potassium salt of Compound A is employed in an amount of from 5 to 60 wt. %;the microcrystalline cellulose is employed in an amount of from 15 to 75 wt. %;the lactose or dibasic calcium phosphate is employed in an amount of from 10 to 50 wt. %;the croscarmellose sodium is employed in an amount of from 1 to 5 wt. %; andthe magnesium stearate is employed in an amount of from 0.5 to 3 wt. %.17. The pharmaceutical composition according to claim 16 , wherein the composition is encapsulated or compressed into a tablet.18. The pharmaceutical composition according to claim 16 , wherein the potassium salt of Compound A is Form 1 potassium salt of Compound A.19. The pharmaceutical composition according to claim 18 , wherein the composition is encapsulated or compressed into a tablet.20. The pharmaceutical composition according to claim 3 , wherein the potassium salt of Compound A is employed in an amount of 50 wt. % and the hydroxyproylmethylcellulose is employed in an amount in a range of from 2 wt. % to 15 wt. %.21. The pharmaceutical composition according to claim 20 , wherein the hydroxyproylmethylcellulose is employed in an amount of 5 wt. %.22. The pharmaceutical composition according to claim 3 , wherein the hydroxyproylmethylcellulose is a low-viscosity hydroxypropylmethylcellulose.23. The pharmaceutical composition according to claim 22 , wherein the potassium salt of Compound A is employed in an amount of 50 wt. % and the low-viscosity hydroxyproylmethylcellulose is employed in an amount in a range of from 2 wt. % to 15 wt. %.24. The pharmaceutical composition according to claim 23 , wherein the low-viscosity hydroxyproylmethylcellulose is employed in an amount of 5 wt. %.25. The pharmaceutical composition according to claim 1 , wherein the potassium salt of Compound A exhibits improved pharmacokinetic properties when administered as a component of this composition.