Purpose: Poor quality medicines, both brands and generics, are those which lack to meet acceptable compendial standards. During the period of latest Arabian Gulf crisis, particularly which is related to Qatar blockade, the availability of prescribed medicine from the existed regional sources was challenging for the State of Qatar. Consequently, search for new alternative sources for both brand and generic medicines was unavoidable. As Diabetes mellitus type II has high prevalence in the State of Qatar, the focus of this study was on Metformin Hydrochloride (MH), as being the most prescribed drug by physicians for Type II Diabetes. As such, the aim of this study was to conduct compendial analysis and quality control testing on local and regional MH multisource generic tablets to assess their in vitro bioequivalence and interchangeability with Glucophage® branded MH tablets.
Methods: US Food & Drug Administration (FDA) and the United States Pharmacopeia (USP 34) guidelines related to compendial drug content, dissolution testing and similarity factor analysis were utilized. An immediate release reference brand MH tablets and generic samples from different sources such as, Saudi Arabia, Oman, Jordan, United Arab Emirates, Egypt, France, Germany, Cyprus and Thailand were subjected to quality control tests. A validity and system suitability tests for MH were conducted for the assertion of the spectrophotometric and chromatographic operating systems. Generic MH samples were blinded and labeled. Content analysis and dissolution testing (according to USP 34) were performed on reference and labeled multisource generic MH tablets. All samples were analyzed using Ultra Performance Liquid Chromatography (UPLC). Data generated for the reference and generic Metformin were compared for similarity using f2 value method.
Results: According to the USP guidelines, each tested product should contain not less than 95% and not more than 105% MH. The results obtained showed that MH products met the USP 34 requirement and criteria in that regard. As for the dissolution testing, 70% of the MH should have been released within 45 minutes. According to this criterion, all products have passed the dissolution testing, but some products showed significantly faster release rate compared to others. As for the similarity factor analysis, the products should achieve a similarity factor (f2) above 50% to be considered similar to the reference MH tablets. All tested products achieved the similarity with the reference MH as indication of the sameness or equivalence of the generics with brand curves. However, it was noticed that higher similarity percentage was achieved by those generics demonstrating the highest drug release rate.
Conclusion: Quality control testing for the multisource MH tablets were conducted and successfully achieved in vitro bioequivalence requirements and therefore can be effectively prescribed interchangeably with the reference branded MH.
Sandi Ali Adib– Qatar University
Aliaa Marie– Research assistant, Pharmaceutics & Polymeric Drug Delivery Research Lab, College of Pharmacy, Qatar University
Mohamed Izham Ibrahim– Social & adminstrative Pharmacy, College of Pharmacy, Qatar University, Doha
Husam Younes– Associate Professor, Qatar University, Ad Dawhah
Sandi Ali-Adib– Qatar University, Doha