Compression coated systems for colonic delivery of 5-fluorouracil.

Abstract

Compression coating is one of the approaches for delaying the release of drugs. The aim of this study was to develop colon-specific compression coated systems of 5-fluorouracil (5-FU) for the treatment of colorectal cancer using xanthan gum, boswellia gum and hydroxypropyl methylcellulose (HPMC) as the coating materials. Core tablets containing 50 mg of 5-FU were prepared by direct compression. The coating of the core tablets was done using different coat weights (230, 250, 275 and 300 mg) and different ratios (1:2, 2:1, 1:3, 1:7 and 3:4) of boswellia gum and xanthan gum and different ratios (1:1, 1:2, 2:1, and 2:3) of boswellia gum and HPMC. In-vitro release studies were carried out using simulated gastric and intestinal fluids, with and without rat caecal contents. Among the different ratios used for coating with boswellia:xanthan gum combination, ratio 1:3 gave the best release profile with the lowest coating weights of 230 mg (7.47 +/- 1.56% in initial 5 h). Further increase in the coat weights to 250, 275 and 300 mg led to drug release of 5.63 +/- 0.53%, 5.09 +/- 1.56% and 4.57 +/- 0.88%, respectively, in the initial 5 h and 96.90 +/- 0.66%, 85.05 +/- 1.01% and 80.22 +/- 0.35%, respectively, in 24 h. When coating was carried out using different ratios of the combination boswellia gum and HPMC, the ratio 2:3 gave the best results among the initial trial batches (7.80 +/- 0.57% in 5 h). Increasing the coat weights to 250, 275 and 300 mg led to drug release of 6.5 +/- 0.27%, 3.70 +/- 2.3% and 2.99 +/- 0.72%, respectively, in the initial 5 h and 96.90 +/- 0.66%, 85.05 +/- 1.01% and 80.22 +/- 0.35%, respectively, in 24 h. In-vitro studies were further carried out in the presence of 2% w/v rat caecal contents, which led to complete release of the drug from the tablets. Therefore, this study lays a basis for use of compression coating of 5-FU as a tool for delaying the release of the drug, which ensures better clinical management of the disease.

• Authors: V R Sinha, Asmita Singh, Sanjay Singh, J R Bhinge
• Journal: The Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 59 Issue 3 Pg. 359-65 (Mar 2007) ISSN: 0022-3573 [Print] England
• PMID: 17331338 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Delayed-Action Preparations
• Excipients
• Polysaccharides, Bacterial
• Tablets, Enteric-Coated
• Hypromellose Derivatives
• Methylcellulose
• xanthan gum
• Fluorouracil

Topics

• Animals
• Antimetabolites, Antineoplastic (administration & dosage, chemistry)
• Boswellia
• Chemistry, Pharmaceutical
• Colon
• Colorectal Neoplasms
• Delayed-Action Preparations
• Drug Delivery Systems
• Excipients
• Fluorouracil (administration & dosage, chemistry)
• Hypromellose Derivatives
• In Vitro Techniques
• Methylcellulose (analogs & derivatives)
• Polysaccharides, Bacterial
• Pressure
• Rats
• Tablets, Enteric-Coated (chemistry)