Dalia Simona Miron1, Flavian Ștefan Rădulescu1, Victor A Voicu1,2, Alina Mînea1, Jean-Michel Cardot3, Vinod P Shah4. 1. Center for Drug Sciences, Faculty of Pharmacy, University of Medicine and Pharmacy Carol Davila Bucharest, Bucharest, Romania. 2. Section of Medical Sciences, Romanian Academy, Bucharest, Romania. 3. Department of Biopharmaceutics and Pharmaceutical Technology, UMR 454 MEDIS, Clermont-Auvergne University, Clermont-Ferrand, France. 4. Pharmaceutical Consultant, North Potomac, MD, USA.
Abstract
OBJECTIVE: The aim was to perform a comparative evaluation of composition and in vitro release performance of multisource acyclovir 5% creams. SIGNIFICANCE: The outcome was analyzed in relation with the principles of the Topical drug Classification System (TCS). METHODS: The in vitro drug release testing (IVRT) was based on selection of an inert artificial membrane and a medium providing sink conditions, and utilizing the vertical diffusion cells. US and European innovator products, with marked difference in excipients, were used as references for the assessment of the in vitro release similarity. The qualitative composition of the topical semisolid products was inventoried, with no quantitative details being available. A Principal Component Analysis was applied by either dichotomy ranking or grouping the individual excipients into categories according to their functional role. RESULTS: The results confirmed the sensitivity and discriminative characteristics of IVRT with respect to the qualitative composition, as well as its relevance in the comparative assessment of multisource drug products beyond the current strict requirements of Q1 and Q2 similarity. CONCLUSIONS: This is in line with the principles of the TCS and with the central role assigned to IVRT.
OBJECTIVE: The aim was to perform a comparative evaluation of composition and in vitro release performance of multisource acyclovir 5% creams. SIGNIFICANCE: The outcome was analyzed in relation with the principles of the Topical drug Classification System (TCS). METHODS: The in vitro drug release testing (IVRT) was based on selection of an inert artificial membrane and a medium providing sink conditions, and utilizing the vertical diffusion cells. US and European innovator products, with marked difference in excipients, were used as references for the assessment of the in vitro release similarity. The qualitative composition of the topical semisolid products was inventoried, with no quantitative details being available. A Principal Component Analysis was applied by either dichotomy ranking or grouping the individual excipients into categories according to their functional role. RESULTS: The results confirmed the sensitivity and discriminative characteristics of IVRT with respect to the qualitative composition, as well as its relevance in the comparative assessment of multisource drug products beyond the current strict requirements of Q1 and Q2 similarity. CONCLUSIONS: This is in line with the principles of the TCS and with the central role assigned to IVRT.
Entities:
Keywords:
Acyclovir cream; Principal Component Analysis (PCA); Topical Drug Classification System (TCS); development of IVR; functional excipients; in vitro release (IVR)