The objective of present study is to design a novel multiparticulate system for colon targeting drug delivery system of cyclophosphamide (CPM) using biodegradable Konjac glucomannan (KGM) as a carrier for colorectal cancer treatment. Glucomannan is a high-molecular weight, water-soluble, non-ionic polysaccharide extracted from the tuber or root of the elephant yam, also known as konjac (Amorphophallus konjac or Amorphophallus rivieri). cyclophosphamide (CPM) has been the only agent with clinically active against colorectal cancer. Different batches of CPM granules were prepared and coated with KGM. Optimized CPM granules (KGM-STMP) were evaluated for flow properties, granular parameters, weight variation and content uniformity. The prepared formulations were subjected for in-vitro drug release studies in simulated gastric and intestinal fluids. It was found that during 2 hr at pH 1.2 HCl (SGF), 3 hr at pH 7.4 phosphate buffer (SIF) only less than 20% of drug was released. The drug release studies was also carried out in simulated colonic fluid (SCF) of pH 6.8 containing β-mannanase in order to mimic the conditions from mouth to colon. Drug release from 5-FU granules coated with KGM-STMP followed diffusion dependent zero order kinetics. Further, report suggested that konjac glucomannan (KGM) was biodegradable and susceptible to the colonic microfloras under anaerobic environments. Spectroscopic, (FTIR), X-ray Diffraction (X-RD) and DSC studies concluded that no polymer-drug interaction was concluded. Accelerated stability studies indicated that no significant changes, in drug release and micrometric patterns for observed when stored at 40± 2ºC / 75±5% RH. Therefore, it was concluded that konjac glucomannan (KGM) is a promising potential carrier for targeting CPM in the vicinity of colon in order to treat colon cancer effectively.
Key words: Cyclophosphamide (CPM), Konjac glucomannan (KGM), multiparticulate system, colon targeted
