Matrix tablets of aspirin and metformin hydrochloride from sodium alginate and admixed with hydroxypropyl cellulose and hydroxypropyl methylcellulose

This investigation deals with an evaluation of sodium alginate (ProtanalRTM LF 240 D) as a hydrophilic matrix forming material for extended release modified drug delivery system using aspirin and metformin HCl as model insoluble and soluble drugs. Nonionic Hydroxypropyl cellulose (HPC H) and hydroxypropyl methylcellulose ((MethocelRTM K100M, HPMC) were included for controlling the drug release at gastro intestinal pH.;Directly compressible formulations for aspirin or metformin HCl matrix tablets were developed using 300 mg of drug and 1% sodium stearyl fumarate as a lubricant. The tablets were compacted on manual compression machine (Globe Pharma) at compression force of 3500 psi. The hardness values of the tablet in kg/cm2 were; 5-6 aspirin-Na alginate, 9-10.5 aspirin-Na alginate-HPC H, 11-12 aspirin-Na alginate-HPMC and 5-6 metformin HCl-Na alginate-HPC H or HPMC systems. Metformin HCl-Na alginate compact were vary fragile upon handling. The dissolution study of the final tablets were carried out using USP method I or II at pH 1.2 and 6.8. For swelling characterization, water uptake study of the polymer matrices without the drug was carried out in water. This study for drug polymer matrices were performed at pH 1.2 and 6.8.;Percent weight gain in case of Na alginate, Na alginate-HPMC and Na alginate-HPC H compact were 332, 308 and 241 respectively. The fairly high swellability of Na alginate together with morphological appearance translucent gelatinous mass was attributed to fairly high solubility. The swelling of the aspirin-Na alginate at pH 1.2 showed 64% weight gain at 2 h and 49% weight gain at 3 h. This was attributed possibly due to the pH difference at periphery and center of the matrix as the medium HCL enter the compact it form alginic acid formed at the periphery and the alginic acid at the center of the matrix attributed to swelling and gel properties of the matrix. At the end of 2 h most of Na alginate was converted to insoluble alginic acid and swelling rate decreased thereafter. Upon change the medium pH 1.2 to 6.8 after 3 h the weight gain continue to decrease due to high solubility of Na alginate and aspirin at pH 6.8. Addition of HPC H or HPMC in the aspirin-Na alginate compact decreased the swelling rate in GI tract pH value 1.2 and 6.8 with the increased rigidity of the matrix both pH. In case of the metformin HCl-Na alginate-HPC H or HPMC compact there was rapid hydration with the weight gain of 40% at 1/2 h then weight gain increase linearly with a decreasing rate at both pH 1.2 and 6.8 up to 6 h. Swelling rate was slightly higher in case of HPMC than that in HPC H system. At the end of 6 h the HPC system matrix appeared slightly less rigid than that of HPMC system.;The aspirin release from Na alginate matrix compact up to 11 h at pH 1.2 was non linear. Inclusion of HPC H (correlation coefficient- 0.9847) or HPMC (correlation coefficient- 0.9929) yielded zero order aspirin release. Dissolution of aspirin at gastric pH (1.2, 0-2 h; 6.8, 2-11 h) from Na alginate matrix compact was non linear. The compact with HPC H and HPMC under the same GI medium condition yielded a linear release profile with correlation coefficient 0.9793 and 0.9956 for HPC H and HPMC systems respectively. Metformin HCl release at pH 1.2 was from Na alginate-HPC H and Na alginate-HPMC system yielded a non linear drug release kinetics. At 2 h the metformin HCl release was 62 and 56% and at 4 h it was 93 and 86% for HPC H and HPMC respectively. Metformin HCl release results from at GI pH 6.8 gave a non linear extended release profile over 11 h period with no significant difference between HPC H and HPMC systems.