| The goal in designing an oral extended release tablet of highly soluble model drug, metformin HCl includes maintaining relatively constant therapeutic blood levels of drug for a desired longer period of time as well as increase the patient compliance by reducing the frequency of dose. Hydrophilic matrices are most widely used because of its simplicity in manufacture. Different hydrophilic polymers such as hydroxypropyl methylcellulose and hydroxypropyl cellulose are used for extended release formulations.;The objective of present research was to develop an extended release metformin HCl-hydroxypropyl methylcellulose/hydroxypropyl cellulose matrix tablets and effect of additives on the drug release mechanism. Various drug:polymer ratios were used to develop an extended release metformin HCl-hydroxypropyl methylcellulose matrix tablets. Metformin HCl-hydroxypropyl methylcellulose matrix tablets were compacted using manual tablet compaction machine by direct compression method. Each matrix tablet contained: 500 mg metformin HCl as a model highly soluble drug, 150 mg hydroxypropyl methylcellulose ( MethocelRTM K100M CR, HPMC) as a hydrophilic and swellable polymer, 150 mg soluble or insoluble additive and 5 mg PruvRTM as a lubricant. Matrix tablet were prepared using magnesium stearate as a lubricant gave hardness below 3 kg/cm 2 thus lubricant was replaced with PruvRTM yielding hardness 7-13 kg/cm2.;Water uptake study of polymer matrices with and without additives was studied. Data indicated that HPMC K100M polymer containing matrix tablets swelled at a higher rate than those compared to additives containing matrix tablets. All matrix tablets showed a non linear release for 1 hour, after 1 hour they showed linear water up take profile.;In vitro dissolution data showed that drug:polymer ratio 3.3:1 yielded 91% metformin HCl release from HPMC matrices over 11 hours. Soluble and insoluble additives affected the metformin HCl release rate from HPMC K100M matrices. T80 (time taken for 80% drug dissolution) are 5.50 hrs, 6 hrs, 7.60 hrs and 8 hrs for reference, microcrystalline cellulose (MCC, pH 200), di-calcium phosphate (DCP) and starch insoluble additives containing metformin HCL matrix tablets. T80 are 5.70 hrs, 6.20 hrs, 5.70 hrs, 7.70 hrs, 8.00 hrs, 8.50 hrs and 9.50 hrs for reference, lactose anhydrous, NaCl, pregelatinized starch, beta-cyclodextrin, povidone and sodium lauryl sulphate (SLS) soluble additives containing metformin HCl matrix tablets, respectively. T80 values demonstrated that starch showed better drug extending release among the insoluble additives by plausibly blocking the channels in the matrix, while TN values demonstrated that SLS showed list release among soluble additives. The SLS had a dramatic drug delaying property which plausibly can be explained on the bulky micellar aggregation within the polymer channel formed in the matrix. Povidone retarded the drug release due to its higher molecular weight. Larger molecular additives acted like insoluble ones, plausibly blocked the channels and yielded lower drug release. T80 of NaCl, beta-cyclodextrin and lactose anhydrous did not show any influence on metformin HCl release from HPMC matrices due to its higher solubility.;Matrix tablets were compacted with HPC-H alone and combination with HPMC hydrophilic polymers at 1:3.3:0, 1:0:3.3, 1:6.6:6.6 and 1:3.3:3.3 drug:HPMC:HPC ratios. After swelling study, it was also observed that HPC matrix was less rigid than that of HPC matrix.;In dissolution study, T80 values of ratios 3.3:1:1, 3.3:0:1, 6.6:1:1 and 3.3:1:1 are 5.70 hrs, 4.25 hrs, 6.25 hrs and 9.60 hrs, respectively. T80 values showed that HPMC matrix swelling rate was higher than that of HPC matrix. In vitro dissolution data of HPMC and/or HPC showed that the drug release rate decreased from HPC to HPMC to HPMC-HPC matrix. |
