Characterization of an extemporaneous liquid formulation of lisinopril.
The stability of lisinopril in an extemporaneously prepared suspension stored at or below 25 degrees C for 28 days under ambient light exposure was studied. A formulation of 1-mg/mL oral suspension was prepared from commercially available 20-mg lisinopril tablets, using Bicitra and Ora-Sweet SF as the compounding vehicles to make a final volume of 200 mL. Individual samples, stored in 8-oz amber polyethylene terephthalate bottles, were used for each test performed. All samples were stored at 25 degrees C. Appropriateness of the extemporaneous preparation method was performed by shaking three lots of each suspension for 30, 60, and 90 seconds. To test the robustness and reproducibility of the method, two chemists prepared the suspensions from the same three lots of lisinopril tablets. Chemical and physical stability were established by analyzing duplicate samples at time zero and after one, two, four, and six weeks. The solubility of lisinopril was tested from suspensions stored for four weeks. In-use stability was also examined over four weeks. Photochemical stability was examined by exposing three batches of the suspension to maximum light stress in accordance with the International Conference on Harmonization. Antimicrobial-effectiveness testing was also conducted with freshly prepared suspensions and suspensions stored for six weeks. The preparation method used was appropriate and effective. Lisinopril is fully dissolved in the suspension matrix. Satisfactory chemical, physical, and microbiological results were obtained after the suspensions were stored for six weeks at 25 degrees C and 35% relative humidity. Lisinopril suspensions extemporaneously prepared from tablets are stable for at least four weeks when stored at or below 25 degrees C under ambient light exposure.
Thompson
Karen C
KC
Merck Research Laboratories, P.O. Box 4, WP78-302, West Point, PA 19486, USA. karen_thompson@merck.com
Zhao
Zhongxi
Z
Mazakas
Jessica M
JM
Beasley
Christopher A
CA
Reed
Robert A
RA
Moser
Cheryl L
CL
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors; D002626:Chemistry, Pharmaceutical; D002648:Child; D004339:Drug Compounding; D004355:Drug Stability; D004356:Drug Storage; D006801:Humans; D017706:Lisinopril; D013535:Suspensions; D013607:Tablets
D000806:Angiotensin-Converting Enzyme Inhibitors; D013535:Suspensions; D013607:Tablets; D017706:Lisinopril