In vitro comparison of guar gum-based matrix and compress ion coated colon-specific diclofenac sodium tablets

Abstract

In order to examine the impact of formulation and processing variables on colonic drug delivery, 2 3 factorial design was applied in this study to develop guar gum-based matrix and compression coated colon-specific tablets. The influence of guar gum loading level on tablet friability was found to be more profound with compression coated tablets whereas best matrix friability was associated with low loading level of MCC regardless of the drug: guar gum ratio. In both cases, increasing the content of guar gum in the formulations has resulted in formation of high strength gel. With matrix formulations, the desired maximum swelling and minimum erosion tendencies among different formulations tested were shown to be associated with high loading level of guar gum. However, with compression coated formulations, the retarding influence (enhancing erosion effect) of MCC on swelling and erosion in these tablet formulation is somewhat noticeable. Although it has been found that the maximum % erosion among these formulations was more sensitive to pH variation, statistical analysis revealedno significant effect of pH variation on swelling and/or erosion behaviors of the tested formulations (p≥0.05). When present as matrixing and/or coating material, content of guar gum was found to be a determining factorfor the in vitro drug delivery control. Addition of 4% w/v of rat caecal content to dissolution medium to mimic colonic fluid was found to enhance the drug release from matrix and/or compression coated guar gumbased tablets. The result has indicated that the enhanced release of the drug inpresence of rat caecal content is due to anaerobic microbialenzymatic action on the swollen guar gum. Moreover, it has been shown that the enhanced effect of rat caecal content on drug release fromguar gum based compression coated formulations is more prominent than with matrix formulations. In vitro drug release studies showed that guar gum matrix and compression coated formulations were able to deliver 78% and 89% of the loaded drug, respectively, inenvironment similar to colonic conditions by the end of 24hrs with a chance for 22% and 11% of the loaded dose to be released before reaching the colon from the two types of formulations, respectively. Consequently, guar gum in form of coating material is confirmed to be more effective than when present as matrixing agent for colonic diclofenac sodium delivery, at least under the conditions of this study