Abstract
Objective: To statistically design, optimize and evaluate a liquid oral, floating in situ gel of metformin hydrochloride (MH) to increase the gastric residence time (the absorption window being the upper part of the duodenum), sustain and modulate the release behavior of the drug. No liquid oral SR formulations of MH are yet available in the market.
 Methods: A simple mixing based ionic cross-linking method was used for the formulation. A Two-square Factorial Design was employed and the effect of sodium alginate and three categorical levels of HPMC (K4M, K100M, E50) on the response variables were studied.
 Results: The optimized formulation gelled instantaneously in simulated gastric fluid and showed>24 h floating. The drug release in 1h was 37.98 %, followed by a moderate sustained release for 12 h. Pharmacodynamic studies showed a significant reduction in blood glucose levels in Wistar rats. Short term preclinical safety studies revealed no toxicity to pancreatic tissues. On the contrary, faster regeneration of the β cells of the islets of Langerhans was observed with the group treated with the optimized formulation. Stability studies revealed a 2-year shelf life.
 Conclusion: An elegant, needle-free, in situ gelling, SR liquid oral of metformin hydrochloride could be developed with drug release modulated as per official specifications for SR formulations of MH. This would be an interesting alternative for geriatric patients who find it difficult to swallow bulky tablets.
Highlights
The successful design and optimization of effective drug delivery systems have become an integral part in improving various parameters such as the degree and rate at which the administered drug reaches the systemic circulation and research is continuously progressing in this area
Characteristic shoulders were observed at 1623 cm-1 for the C=N stretching, 1544 cm-1 for the N-H bending, 1164 cm1 for the of the C-N stretch, 3288 cm-1 for the N-H stretching respectively. These bands were observed for the physical mixture of polymers along with metformin hydrochloride (MH), confirming that there was no interaction between MH, polymers and excipients used and that they were compatible with the drug
Metformin HCl liquid oral in situ gel
Summary
The successful design and optimization of effective drug delivery systems have become an integral part in improving various parameters such as the degree and rate at which the administered drug reaches the systemic circulation and research is continuously progressing in this area. Metformin hydrochloride is an oral hypoglycemic agent and the first drug of choice to treat patients with Type II diabetes. It has an absolute oral bioavailability of 40% to 60%. It is highly hydrophilic with gastrointestinal absorption occurring mainly in the upper part of the intestine with peak plasma concentrations (Cmax) at 4.8 h. It has a short half-life of 1.5 to 4.5 h and the development of gastro retentive systems of the drug would help sustain the drug release and improving oral bioavailability. When large doses of MH are needed, the frequency of dosing may be 2 to 3 times a day which may reduce patient compliance and liquid oral sustainedrelease (SR) formulations that give once a day dosing would be preferable
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