Colonic drug delivery of 5-fluorouracil: an in vitro evaluation

• Published in: International journal of pharmaceutics 2004-01, Vol.269 (1), p.101-108
• Main Authors: Sinha, V.R, Mittal, B.R, Bhutani, K.K, Kumria, Rachna
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; Administration, Oral; Animals; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacokinetics; Biological and medical sciences; Cecum - metabolism; Chemistry, Pharmaceutical; Chemotherapy; Chromatography, High Pressure Liquid; Colon specific drug delivery; Colorectal cancer; Delayed-Action Preparations; Drug Delivery Systems; Excipients; Fluorouracil - administration & dosage; Fluorouracil - chemistry; Fluorouracil - pharmacokinetics; Guar gum; Humans; In Vitro Techniques; Medical sciences; Pharmacology. Drug treatments; Polysaccharides, Bacterial; Rats; Rats, Wistar; Tablets, Enteric-Coated; Time Factors; Xanthan gum
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2003.09.036

Compression coating has been found to be useful for colonic drug delivery. The aim of the present investigation was to design a formulation with a considerably reduced coat weight and gum concentration for colonic delivery of 5-fluorouracil for the treatment of colorectal cancer. Rapidly disintegrating core tablets containing 50 mg of 5-fluorouracil were prepared and compression coating with 175 mg of granules containing a mixture of xanthan gum (XG) and guar gum (GG) in varying proportions was done. With this coat weight, a highly retarded drug release was observed. After 24 h of dissolution the mean percent drug release from the compression coated XG:GG 20:20, 20:10 and 10:20 tablets were found to be around 18±1.23%, 20±1.54% and 30±1.77%, respectively. So, the coat weight was further reduced to 150 mg. It was observed that reduction of coat weight did not affect the initial drug release rate in simulated upper gastrointestinal tract (GIT) conditions. At the end of 24 h of dissolution the amount of drug released increased to 25±1.22%, 36.6±1.89% and 42.6±2.22%, respectively in XG:GG 20:20, 20:10 and 10:20 tablets. Studies of XG:GG (10:20) tablets in presence of colonic contents showed an increased cumulative percent drug release of 67.2±5.23% in presence of 2% cecal content and 80.34±3.89% in presence of 4% cecal content after 19 h of incubation.