Development and in-vitro drug release studies of methotrexate from modified pulsatile release guar gum based enteric coated capsules for colon specific delivery

The objective of the present study was to develop pulsatile release based enteric coated capsules for site specific delivery of Methotrexate to colon which is used in treatment of colo-rectal cancer. The modified formulation was capable of delaying onset of drug release for a programmed lag time period of 3-5 h in the simulated physiological environment of upper gastrointestinal tracts depends on coating ratios of HPMC (inner coating) and Eudragit-S100 (outer coating). Dissolution studies demonstrates that, polymeric coated formulations of HPMC and pH sensitive Eudragit-S 100 were gastro-resistance for 2 h at pH 1.2 and further for 3 h at pH 6.8, since they released only 3-7 % of drug in physiological environment of stomach and small intestine. The complete disintegration occurred only after a certain lag time of 4 to 5 h. The systems having optimized 30% of guar gum and polymeric coating ratios of 2: 4, 3: 2, 3: 4 and 4: 3 without and with 4% rat caecal content in PBS 7.2 pH released approximately up to 33% and 92% of drug as compared to control during 24 h of in-vitro dissolution studies, which suggest the susceptibility of polymers to the colonic microflora and likely to be used for local action in colon. DSC thermogram analysis shows no possibility of interaction between drug and polymers used in the study. The study result demonstrated that the developed system can be a promising device for targeting of methotrexate to colonic region for treatment of colorectal cancer.