Formulation factors for preparing ocular biodegradable delivery system of 5-fluorouracil microparticles.
Microparticles containing 5-fluorouracil (5-FU) were prepared using poly(DL-lactide-co-glycolide) with an oil-in-oil emulsion/solvent extraction technique. Particle characteristics including size distribution, 5-FU loading efficiencies, in vitro release and degradation were investigated. The dispersed phase was composed of PLG dissolved in dichloromethane, and the continuous phase was paraffin oil containing lecithin. 5-FU was successfully entrapped in the microparticles with trapping efficiencies up to 76%, loading level 10% w/v, and particle size 3 microm. Release profiles of 5-FU loaded microparticles were determined to follow a first-order-time relationship. An optimized preparation of 5-FU microparticles was achieved and was capable of controlling the release of 5-FU over 21 days with an in vitro delivery rate of 0.4 microg 5-FU/mg particles/day in the study. Preliminary animal studies indicated that the 5-FU loaded microparticles as an ocular delivery system showed no ocular toxicity and no significant inflammatory response in rabbits for 2 months. The 5-FU loaded microparticles approach, with PLG, might be a potential for the application of long-term delivery of hydrophilic drugs in the eye.
Yeh
M K
MK
Department of Clinical Pharmacy, Tri-service General Hospital, Taipei, Taiwan.
Tung
S M
SM
Lu
D W
DW
Chen
J L
JL
Chiang
C H
CH
D000818:Animals; D000963:Antimetabolites / Q000008:administration & dosage / Q000493:pharmacokinetics; D001672:Biocompatible Materials; D001673:Biodegradation, Environmental; D002214:Capsules; D003131:Combined Modality Therapy; D004339:Drug Compounding / Q000379:methods*; D016503:Drug Delivery Systems; D004343:Drug Implants; D018463:Filtering Surgery; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005901:Glaucoma / Q000188:drug therapy / Q000601:surgery; D006801:Humans; D066298:In Vitro Techniques; D019344:Lactic Acid; D008855:Microscopy, Electron, Scanning; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011817:Rabbits
D000963:Antimetabolites; D001672:Biocompatible Materials; D002214:Capsules; D004343:Drug Implants; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005472:Fluorouracil