Formulation optimization and release kinetics of Metronidazole matrix, compression and spray coated tablets: Effect of organic acid on colon targeted drug delivery system

Abstract

Amoebiasis is an infection of the large intestine caused by Entamoeba histolytica, and it is mainly present in the intra-intestinal lumen. The efficient treatment of amoebiasis and other colonic infections could be achieved by targeting the drug to the colon. Metronidazole is the drug of choice for intestinal amoebiasis and other colon infections and the best approach for this drug is to target the drug delivery to colon which would make the drug effective with low dose and prevent the potential hazards observed in conventional dose. Moreover, addition of suitable organic acid in the formulation could enhance the drug solubility where less free aqueous is present than intestine. The aim of the present investigation was to formulate matrix formulations using different concentrations of guar gum and pectin with suitable organic acid and to prevent the premature drug release in the GI tract, the matrix formulations further taken for compression and spray coating to test the suitability for targeted drug delivery to the colon. The release kinetics of the formulations was performed using PCP-Disso Excel software. All the Matrix, Compression coated and Spray coated formulations were showed the desired physicochemical properties as per the official limits. Based on the drug release study in pH 1.2 (0.1N HCl), Phosphate buffer pH 7.4 and 6.8, the three MGT F8, MGTE F20, and MGTES F32 were found to be best and they were taken for further release study in phosphate buffer pH 6.8 with rat cecal content (4% w/v). The formulations MGTE F20 (r² - 0.9986, n - 1.0601) and MGTES F32 (r² -0.9974, n - 1.1501) were shown zero order release in terms of its kinetic release. Guar gum (40%) and Tartaric acid (80mg) was found to be suitable for this formulation and further gastrointestinal resistant coating is necessary for targeting the drug release. Hence, this special drug delivery system is needed to minimize the hazardous effects and to increase the effectiveness of the drug.