Category: Formulation and Quality
Purpose: Substandard medicines, both brands and generics, are those which are produced by legitimate manufacturers but fail to meet acceptable compendial requirements. During the period of the latest Arabian Gulf crisis, particularly which is related to Qatar blockade, the availability of prescribed medicine from the existed regional and international sources was challenging for the State of Qatar. Consequently, immediate search for new alternative sources for both brand and generic medicines was unavoidable. As Atrovastatin Calcium (AC) is highly prescribed in the State of Qatar to treat high cholesterol, and to lower the risk of stroke, heart attack, or other cardiovascular complications in people with type-2 diabetes, the aim of this study was to conduct compendial analysis and quality control testing on regional and global AC multi-source generic tablets to assess their in vitro bioequivalence and interchangeability with Lipitor ® branded AC tablets.
Methods: US Food & Drug Administration (FDA), the United States Pharmacopeia (USP 34) guidelines and the monograph revision bulletin released on May 1, 2018 related to compendial drug content, dissolution testing and similarity factor analysis were utilized. Brand AC tablets and generic samples from different sources such as, Oman, Jordan, Spain and Germany were subjected to quality control tests. A validity and system suitability tests for AC were conducted for the assertion of the spectrophotometric and chromatographic operating systems. Generic AC samples were blinded and labeled. Content analysis and dissolution testing (according to USP 34) were performed on reference and labeled multi-source generic AC tablets. All samples were analyzed using High Performance Liquid Chromatography (HPLC) equipped with PDA detector. Data generated for the reference and generic AC were compared for similarity using F2 value method.
Results: According to the USP guidelines, each tested product should contain not less than 94.5% and not more than 105% AC. The results obtained showed that AC products met the USP requirement and criteria in that regard. As for the dissolution testing, 80% of the AC should have been released within 15 minutes. According to this criterion, all products have passed the dissolution testing and showed similarity in release rate. As for the similarity factor analysis, the products should achieve a similarity factor (f2) above 50% to be considered similar to the reference AC tablets. All tested products achieved similarity with the reference AC as indication of the sameness or equivalence of the generics with brand curves. However, it was noticed that lower similarity percentage was achieved by those generics demonstrating lower drug release rate .
Conclusion: Quality control testing for the multi-source AC tablets were conducted and successfully achieved in vitro bioequivalence requirements and therefore can be effectively prescribed interchangeably with the reference branded AC
Alia Murai– Doha, Ad Dawhah, Qatar
Sandi Ali-Adib– Qatar University, Doha, Ad Dawhah, Qatar
Luay S’efan– Doha, Ad Dawhah, Qatar
Mohamed Izham Ibrahim– Social & adminstrative Pharmacy, College of Pharmacy, Qatar University, Doha, Ad Dawhah, Qatar