Abstract
The potential of a new poly(magnesium acrylate) hydrogel (PAMgA) as a pharmaceutical excipient for the elaboration of matrix tablets for the extended release of highly hydrophilic drugs was evaluated. The polymer was synthetized with two different crosslinking degrees that were characterized by FTIR and DSC. Their acute oral toxicity was determined in a mouse model, showing no toxicity at doses up to 10 g/kg. Matrix tablets were prepared using metformin hydrochloride as a model drug and the mechanisms involved in drug release (swelling and/or erosion) were investigated using biorrelevant media. This new hydrogel effectively controlled the release of small and highly hydrophilic molecules as metformin, when formulated in matrix tablets for oral administration. The rate of metformin release from PAMgA matrices was mainly controlled by its diffusion through the gel layer (Fickian diffusion). The swelling capacity and the erosion of the matrix tablets influenced the metformin release rate, that was slower at pH 6.8, where polymer swelling is more intensive, than in gastric medium, where matrix erosion is slightly more rapid. The crosslinking degree of the polymer significantly influenced its swelling capacity in acid pH, where swelling is moderate, but not in intestinal fluid, where swelling is more intense.
Highlights
Metformin HCl (1,1-dimethylbiguanide hydrochloride), belonging to the group of oral hypoglycaemic drugs, is the most used oral treatment in patients with type 2 diabetes mellitus
In immediate-release dosage forms, metformin exhibits an oral bioavailability of 55 ± 16% because, on the one hand, it presents an absorption window limited to the upper segments of the intestinal tract [2]; and, on the other hand, the transporters mediating its absorption are saturable, which makes metformin bioavailability dose-dependent [3]
Ryeiesludltsobtained in the synthesis of the polymer was high for both crosslinking degrees, but higher f3o.1r.PCAhaMragctAeriz4a0ti(o8n5o.f0t%he)Ptohlyamnefror PAMgA 5 (71.2%)
Summary
Metformin HCl (1,1-dimethylbiguanide hydrochloride), belonging to the group of oral hypoglycaemic drugs, is the most used oral treatment in patients with type 2 diabetes mellitus. It exerts its pharmacological action mainly by decreasing both hepatic gluconeogenesis and glycogenolysis. Metformin has low potency and a short biological half-life of approximately 2 h [1]. It is used in therapeutics at high-doses and short dose intervals: the usual doses vary between 500 and 1000 mg and they must be administered from 2 to 3 times a day. The presence of high concentrations of metformin in the bowel produces gastrointestinal side effects such as diarrhoea, flatulence, vomiting and nausea
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