In vitro drug release studies on guar gum-based colon targeted oral drug delivery systems of 5-fluorouracil.
Intravenous administration of 5-fluorouracil for colon cancer therapy produces severe systemic side-effects due to its cytotoxic effect on normal cells. The broad objective of the present study was to develop novel tablet formulations for site-specific delivery of 5-fluorouracil to the colon without the drug being released in the stomach or small intestine using guar gum as a carrier. Fast-disintegrating 5-fluorouracil core tablets were compression coated with 60% (FHV-60), 70% (FHV-70) and 80% (FHV-80) of guar gum, and were subjected to in vitro drug release studies. The amount of 5-fluorouracil released from the compression-coated tablets in the dissolution medium at different time intervals was estimated by a HPLC method. Guar gum compression-coated tablets released only 2.5-4% of the 5-fluorouracil in simulated GI fluids. When the dissolution study was continued in simulated colonic fluids (4% w/v rat caecal content medium) the compression-coated FHV-60, FHV-70 and FHV-80 tablets released another 70, 55 and 41% of the 5-fluorouracil respectively. The results of the study show that compression-coated tablets containing 80% (FHV-80) of guar gum are most likely to provide targeting of 5-fluorouracil for local action in the colon, since they released only 2.38% of the drug in the physiological environment of the stomach and small intestine. The FHV-80 formulation showed no change either in physical appearance, drug content or dissolution pattern after storage at 40 degrees C/RH 75% for 6 months. The differential scanning calorimetric study showed that 5-fluorouracil did not interact with the formulation excipients used in the study.
Department of Pharmaceutical Sciences, College of Engineering, Andhra University, Visakhapatnam, 530 003, India. krishnaysr112@rediffmail.com
Y S R
YS
Krishnaiah
V
V
Satyanarayana
B
B
Dinesh Kumar
R S
RS
Karthikeyan
D000284:Administration, Oral; D000818:Animals; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005685:Galactans / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008351:Mannans / Q000008:administration & dosage* / Q000493:pharmacokinetics; D053149:Plant Gums; D051381:Rats; D013608:Tablets, Enteric-Coated
D005685:Galactans; D008351:Mannans; D053149:Plant Gums; D013608:Tablets, Enteric-Coated; C007894:guar gum; D005472:Fluorouracil