Physicochemical and in vitro dissolution properties of some metformin tablet preparations on the Ghanaian Market

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Metformin hydrochloride is an oral hypoglycaemic agent belonging to the class of drugs called biguanides and the first line drug for the management of type 2 diabetes particularly in overweight and obese patients. There are numerous generics of metformin hydrochloride t ablets available within the health delivery system in Ghana and globally, which places medical practitioners in a dilemma of generic substitution. The study sought to determine the physicochemical equivalence and to establish whether or not the selected brands were interchangeable based on in vitro dissolution properties. Fourteen brands of metformin hydrochloride tablets plus the innovator brand, Glucophage were purchased from selected licensed pharmacies within the country and they were all conventional, immediate-release oral dosage forms. Coding of all the brands was done t o avoid bias and the genuineness of the samples was determined using infra -red spectroscopy and thin layer chromatography. Pharmacopoeia tests such as friability, hardness, uniformity of weight, disintegration and a ssay were used to assess the physicochemical equivalence of the various brands of metformin hydrochloride tablets. In vitro dissolution testing was conducted using the paddle method at six time points to obtain their dissolution profiles which were subjected to analysis involving dissolution efficiency, model-independent and ANOVA-based methods. Lastly, Biopharmaceutics classification system based biowaiver conditions were applied to the various brands as a surrogate for bioequivalence studies. All the brands of metformin hydrochloride tablets sampled complied with the official specifications for identification, disintegration, uniformity of weight, hardness and thickness tests. However, for the friability test, brand M9 failed to meet the required specification. Both UV spectroscopy and HPLC were used for the assay analysis and all the brands except three v (M5, M9 and M12) had values which fell within the specification range for assay in the British Pharmacopoeia. All the brands met the pharmacopoeia criterion for dissolution rate test for conventional immediate release tablets. All the brands with the exception of three (M5, M9 and M12) passed all the official tests and therefore, they could be regarded as having the same physicochemical properties. Brands M6 and M11 had the highest dissolution efficiency of 95% while M9 had the lowest dissolution efficiency of 83.8%. From f1 and f 2 analysis, the dissolution profiles of seven brands were similar to that of the re ference brand which indicated that they could be used interchangeably in clinical practice. However, using one -way ANOVA analysis followed by Dunnett’s multiple comparison test, only the dissolution profiles of five brands were significantly different from that of the reference drug. Non e of the brands including the reference drug was able to meet the criteria for BCS -based biowaiver for very rapidly or rapidly dissolving tablets and therefore, the need for in vivo studies to establish the bioequivalence of these brands cannot be overemphasized.
A thesis submitted to the School of Graduate Studies in partial fulfilment of the requirements for the degree of Master of Philosophy in Pharmaceutics