Development of an extended release metformin HCl-hydroxypropyl cellulose matrix tablets and effect of additives on the drug release mechanism

A metformin HCl extended release tablet is the convenient dosage form to avoid frequent dosing and to improve patient compliance. The goal in developing an oral extended release tablets includes maintaining relatively constant therapeutic blood levels of the drug for an extended period of time. Hydrophilic matrices are widely used because of their simplicity in manufacture.;The current work was intended to develop an extended release tablet of metformin HCl, a model highly water soluble drug, from hydroxypropyl cellulose (HPC) matrices. Various drug:polymer ratios were used to develop an extended release metformin HCl-HPC matrix tablets. Metformin HCl-HPC matrix tablets were compacted using manual tablet compaction machine by wet granulation and direct compression method. Each matrix tablet contained: 300 mg metformin HCl as a model highly soluble drug, 150 mg HPC, a hydrophilic and swellable polymer, 50 mg soluble or insoluble additive and 5 mg PruvRTM as a lubricant. Metformin HCl matrix tablets designed with HPC as the polymer in the drug:polymer ratio of 2:1 using wet granulation gave extended drug release over 11 hr so this formulation was used as reference. Preliminary studied showed that the drug: polymer of 3:1 gave the same release as that of 2:1. HPC M (medium viscosity) gave the same drug release kinetics as that of HPC H so HPC H was used. Initially metformin HCl-HPC matrix tablets prepared using magnesium stearate were found to give low hardness of under 3 kg/cm 2 hence sodium stearyl fumarate was used as the lubricant.;The effect of soluble or insoluble additives and granulating vehicle was studied on the drug release rate. The additives were added at 10% w/w in the formulations. Effect of different granulation techniques on drug release rate was also studied. Experiments were done to study the water uptake ability of metformin HCl-hydroxypropyl cellulose matrix tablets, the effect of additives, granulating vehicle, and granulating techniques on the hydration and dissolution rate. Both the granulation technique showed a wide variety of the same polymer hydration rate, with the wet granulation method the tablet showed very slow hydration and swelling during the first hour in a nonlinear manner. After one hour, it showed the linear water uptake profile. The tablets prepared with direct compression method showed a non linear water uptake profile with the tablets almost completely hydrated at the end of 3 hrs forming a translucent gelatinous matrix. In general the swelling and hydration rate of tablet was directly related to the solubility of additives added to the tablets with the exception of povidone and sodium lauryl sulphate, a soluble additive which showed remarkable slower water uptake as compared to the one without it. Directly compressed metformin HCl with SLS showed the most delay in water uptake which could be explained on the basis of more water affinity of SLS then that of HPC.;In vitro dissolution data of metformin HCl-HPC matrix tablets showed a wide variety of release profile. The results demonstrated that the granules prepared using IPA show a better extending effect over those prepared using water as the granulating vehicle. The solubility of the additives is directly related to metformin HCl release rate. Among soluble additives beta-cyclodextrin showed the least drug extending ability whereas in insoluble additive starch showed the better drug extending ability by plausibly blocking the channels in the matrix Exceptionally SLS a soluble additive demonstrated a pronounced reduction in the drug release rate from directly compressible metformin HCl tablet as compared to that of any other formulation due to its high hydrophilicity.