Claims for Patent: 4,743,450

Summary for Patent: 4,743,450

Title:	Stabilized compositions
Abstract:	The cyclization, hydrolysis, and coloration of certain ACE inhibitors is minimized when they are formulated with a metal-containing stabilizer and a saccharide.
Inventor(s):	Harris; Michael (Hackettstown, NJ), Hokanson; Gerard (Long Valley, NJ), Murthy; Kuchi (Morris Plains, NJ), Reisch; Robert (Haledon, NJ), Waldman; Frank (Wayne, NJ)
Assignee:	Warner-Lambert Company (Morris Plains, NJ)
Application Number:	07/017,962
Patent Claims:	1. A pharmaceutical composition which contains: (a) a drug component which comprises a suitable amount of an ACE inhibitor which is susceptible to cyclization, hydrolysis, and discoloration, (b) a suitable amount of an alkali or alkaline earth metal carbonate to inhibit cyclization and discoloration, and (c) a suitable amount of a saccharide to inhibit hydrolysis. 2. The composition of claim 1 wherein (a) is enalapril or a pharmaceutically acceptable acid addition salt thereof. 3. The composition of claim 1 wherein (a) contains at least one additional drug. 4. The composition of claim 1 wherein (b) contains magnesium carbonate. 5. The composition of claim 1 wherein (c) contains at least one of mannitol and lactose. 6. The composition of claim 1 wherein the composition also contains at least one material selected from the group consisting of: binders, disintegrants, and lubricants. 7. The composition of claim 1 wherein (a) is a compound of the formula ##STR2## wherein A is absent, a fused five, six, or seven-membered cycloaliphatic ring or a fused benzene ring which is unsubstituted or substituted by one or two alkoxy groups having one to four carbon atoms; n is zero or one, and R is hydrogen or alkyl having one to five carbon atoms, or a pharmaceutically acceptable acid addition salt thereof. 8. The composition of claim 7 wherein A is absent, a fused five or six-membered cycloaliphatic ring or a fused benzene ring which is unsubstituted or substituted by two methoxy groups; n is zero or one, and R is hydrogen or ethyl, or a pharmaceutically acceptable acid addition salt thereof. 9. The composition of claim 1 wherein (a) is quinapril, or a pharmaceutically acceptable acid addition salt thereof. 10. The composition of claim 1 wherein (a) is quinapril hydrochloride. 11. The composition of claim 1 wherein (a) is indolapril or a pharmaceutically acceptable acid addition salt thereof. 12. A tablet containing the composition of claim 1. 13. A tablet containing the composition of claim 3. 14. A candy formulation containing the composition of claim 1. 15. A candy formulation containing the composition of claim 3. 16. A process for stabilizing an ACE inhibitor drug against cyclization which comprises the step of contacting the drug with: (a) a suitable amount of an alkali or alkaline earth-metal carbonate and, (b) one or more saccharides. 17. The process of claim 16 wherein the drug is selected from the group consisting of quinapril, enalapril, and indolapril, or a pharmaceutically acceptable acid addition salt thereof.