Claims for Patent: 8,541,399

Summary for Patent: 8,541,399

Title:	Solvent-based sterilisation of pharmaceuticals
Abstract:	A sterile composition of a pharmaceutical compound is prepared by combining solvent with a non-sterile pharmaceutical compound to form a solution and filtering to yield a sterile pharmaceutical compound, optionally removing all or part of the solvent, and under sterile conditions combining the compound with a pharmaceutically acceptable carrier.
Inventor(s):	Bhatarah; Parveen (Stevenage, GB), Greenwood; Kenneth Alan (London, GB)
Assignee:	Resolution Chemicals Limited (Stevenage Hertfordshire, GB)
Application Number:	10/505,137
Patent Claims:	1. A method for preparing a sterile pharmaceutical composition of a steroid comprising: (i) dissolving a non-sterile steroid in a non-aqueous solvent to yield a solution of the steroid, (ii) filtering the solution of (i) to yield a sterile solution, (iii) combining the sterile solution of (ii) with sterile water to form a sterile aqueous suspension, (iv) treating the sterile aqueous suspension of (iii) to obtain a sterile aqueous suspension with a particle size distribution having a mass median diameter less than 10 .mu.m, (v) under sterile conditions combining the sterile aqueous suspension of (iv) with a pharmaceutically acceptable carrier to yield a sterile pharmaceutical composition comprising a sterile aqueous suspension of the steroid having a mass median diameter less than 10 .mu.m, and (vi) storing the sterile pharmaceutical composition of (v) in sterile containers. 2. The method of claim 1, wherein the non-sterile steroid is a powder. 3. The method of claim 2, wherein the powder is a micronized powder. 4. The method of claim 1, wherein the steroid is budesonide. 5. The method of claim 1, wherein the solvent comprises an alcohol. 6. The method of claim 1, wherein the solvent comprises a Class 3 solvent. 7. The method of claim 1, wherein the solvent comprises a Class 2 solvent. 8. The method of claim 1, comprising combining solvent with the steroid at a temperature from 20.degree. C. below the boiling point of the solvent up to its boiling point. 9. The method of claim 1, wherein the solvent is at reflux. 10. The method of claim 1, comprising filtering the solution through a filter having a pore size of 0.2 .mu.m or less. 11. The method of claim 1, wherein the sterile water contains a surfactant. 12. The method of claim 1, comprising treating the suspension to obtain a particle size distribution having a mass median diameter in the range 1-5 .mu.m. 13. The method of claim 12, comprising treating the suspension to obtain a particle size distribution having a mass median diameter in the range 2-3 .mu.m. 14. The method of claim 1, comprising storing the sterile composition in sterile ampoules. 15. A method for preparing a sterile suspension of budesonide, comprising: (i) dissolving non-sterile budesonide in a non-aqueous solvent to yield a budesonide solution, (ii) filtering the solution of (i) to yield a sterile solution, (iii) combining the sterile solution of (ii) with sterile water to form a sterile aqueous suspension of budesonide, (iv) treating the sterile aqueous suspension of (iii) to obtain a sterile aqueous suspension with a particle size distribution having a mass median diameter less than 10 .mu.m, (v) under sterile conditions combining the sterile aqueous suspension of (iv) with a pharmaceutically acceptable carrier to yield a sterile pharmaceutical composition comprising the sterile aqueous suspension of budesonide having a mass median diameter less than 10 .mu.m, and (vi) storing the sterile pharmaceutical composition of (v) in sterile containers. 16. The method of claim 15, wherein the solvent comprises an alcohol. 17. The method of claim 15, comprising filtering the solution through a filter having a pore size of 0.2 .mu.m or less. 18. The method of claim 17, comprising treating the suspension to obtain a particle size distribution having a mass median diameter in the range 1-5 .mu.m. 19. The method of claim 17, comprising treating the suspension to obtain a particle size distribution having a mass median diameter in the range 2-3 .mu.m. 20. A method for preparing a sterile pharmaceutical composition of a steroid comprising: (i) dissolving a non-sterile steroid in a non-aqueous solvent to yield a solution of the steroid, (ii) filtering the solution of (i) to yield a sterile solution, (iii) combining the sterile solution of (ii) with sterile water to form a sterile aqueous suspension, (iv) removing all or part of the non-aqueous solvent from the sterile aqueous suspension of (iii) to yield a sterile aqueous suspension having reduced non-aqueous solvent content, (v) treating the sterile aqueous suspension having reduced non-aqueous solvent content of (iv) to obtain a sterile aqueous suspension with a particle size distribution having a mass median diameter less than 10 .mu.m, (vi) under sterile conditions combining the sterile aqueous suspension of (v) with a pharmaceutically acceptable carrier to yield a sterile pharmaceutical composition comprising a sterile aqueous suspension of the steroid having a mass median diameter less than 10 .mu.m, and (vii) storing the sterile pharmaceutical composition of (vi) in sterile containers. 21. A method for preparing a sterile pharmaceutical composition of budesonide comprising: (i) dissolving a non-sterile budesonide in a non-aqueous solvent to yield a budesonide solution, (ii) filtering the solution of (i) to yield a sterile solution, (iii) combining the sterile solution of (ii) with sterile water to form a sterile aqueous suspension of budesonide, (iv) removing all or part of the non-aqueous solvent from the sterile aqueous suspension of (iii) to yield a sterile aqueous suspension having reduced non-aqueous solvent content, (v) treating the sterile aqueous suspension having reduced non-aqueous solvent content of (iv) to obtain a sterile aqueous suspension with a particle size distribution having a mass median diameter less than 10 .mu.m, (vi) under sterile conditions combining the sterile aqueous suspension of (v) with a pharmaceutically acceptable carrier to yield a sterile pharmaceutical composition comprising a sterile aqueous suspension of budesonide having a mass median diameter less than 10 .mu.m, and (vii) storing the sterile pharmaceutical composition of (vi) in sterile containers. 22. The method of claim 15, comprising storing the sterile composition in sterile ampoules. 23. The method of claim 20, comprising storing the sterile composition in sterile ampoules. 24. The method of claim 21, comprising storing the sterile composition in sterile ampoules. 25. The method of claim 20, comprising removing solvent under reduced pressure. 26. The method of claim 20, comprising removing solvent at atmospheric pressure.

Details for Patent 8,541,399

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	ZOSTAVAX	zoster vaccine live	For Injection	125123	05/25/2006		2022-02-19