Physicochemical and in vitro dissolution properties of some metformin tablet preparations on the Ghanaian Market
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Date
2015-02-26
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Abstract
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.
Description
A thesis submitted to the School of Graduate Studies in
partial fulfilment of the requirements for the degree of
Master of Philosophy in Pharmaceutics