Pectin/Ethylcellulose as film coatings for colon-specific drug delivery: preparation and in vitro evaluation using 5-fluorouracil pellets.
The aim of the present study is to develop colon-targeted drug delivery systems for 5-fluorouracil using pectin combined with ethylcellulose as a film coat with fluidized bed coater. Pellets (0.8-1.0 mm in diameter) containing 40% 5-fluorouracil and 60% microcrystalline cellulose were prepared by extrusion and spheronization. Film-coated pellets of 5-fluorouracil containing various proportions (1:0, 0:1, 1:1, 1:2, w/w) of pectin and ethylcellulose (Surelease) were prepared and subjected to in vitro drug release. The amount of 5-fluorouracil released from pellets at different time intervals was estimated by high-performance liquid chromatography. Drug release was assessed using flow testing in the presence and absence of rat caecal contents. The film thickness is expressed as the theoretical percentage of the weight gained (TWG-%) used relative to the weight of the coated pellets. Coated pellets with pectin alone and TWG-20% released 100% of the 5-fluorouracil in the simulated gastric and small intestinal conditions and failed to control the drug release in the first 5 h of the dissolution study in the simulated gastric and small intestinal conditions; while coated pellets with ethylcellulose alone and TWG-20% released 11.7 +/- 0.9% of the 5-fluorourail at the end of 24 h. When the ratio of pectin to Surelease was 1:1 (w/w) and film coat TWG-20%, the release was rapid and was accompanied by splitting of the coat. When the ratio of pectin to Surelease was 1:2 (w/w) and film coat TWG-13% and TWG-20%, the formulations released 9.8 +/- 0.7% and 4.1 +/- 0.4%, respectively, of 5-fluorouracil in the first 5 h of the dissolution study in the simulated gastric and small intestinal conditions. When the dissolution study was continued in simulated colonic fluids (4% w/v rat caecal content medium) for another 19 h, the film coat with the formulations of TWG-13% and TWG-20% released 96 +/- 1.3% and 85.0 +/- 0.3%, respectively, of 5-fluorourail in simulated colonic fluids at the end of 24 h of the dissolution study, whereas in the control study the formulations released 51.4 +/- 1.0% and 34 +/- 0.5%, respectively, of 5-fluorouracil in absence of rat caecal contents at the end of 24 h. The results of the study show that the formulation of TWG-20% (pectin to Surelease 1:2, w/w) is most likely to provide targeting of 5-fluorouracil for local action in the colon, as it released only 4.1 +/- 0.4% of the drug in the simulated gastric and small intestinal conditions, and it released 85.0 +/- 0.3% of 5-fluorourail in simulated colonic fluids at the end of 24 h. The 5-fluorouracil-coated pellets showed no change in physical appearance, drug content, or dissolution pattern after storage at 40 degrees C/75% relative humidity for 6 months. Differential scanning calorimetric study indicated no possibility of interaction between 5-fluorouracil and pectin or other excipients used in the coated pellets.
Wei
He
H
Department of Pharmaceutics, School of Pharmaceutical Science, Hebei Medical University, ShiJiaZhuang, P.R. China.
Qing
Du
D
De-Ying
Cao
C
Bai
Xiang
X
Fanli-Fang
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D002152:Calorimetry, Differential Scanning; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003106:Colon / Q000378:metabolism*; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D005243:Feces / Q000737:chemistry; D005472:Fluorouracil / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D010368:Pectins / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013608:Tablets, Enteric-Coated; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors
D000964:Antimetabolites, Antineoplastic; D005079:Excipients; D013608:Tablets, Enteric-Coated; C013517:ethyl cellulose; D010368:Pectins; D002482:Cellulose; C109691:microcrystalline cellulose; D005472:Fluorouracil