A poly(ortho ester) designed for combined ocular delivery of dexamethasone sodium phosphate and 5-fluorouracil: subconjunctival tolerance and in vitro release

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 50; no. 2; pp. 251 - 255
• Main Authors: Zignani, M, Einmahl, S, Baeyens, V, Varesio, E, Veuthey, J.L, Anderson, J, Heller, J, Tabatabay, C, Gurny, R
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01-09-2000; Elsevier Science
• Subjects: 5-Fluorouracil; Animals; Biocompatibility; Biocompatible Materials - administration & dosage; Bioerodible polymers; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Capillary electrophoresis; Conjunctiva - metabolism; Delayed-Action Preparations; Dexamethasone; Dexamethasone - administration & dosage; Dexamethasone - analogs & derivatives; Dexamethasone - chemistry; Dexamethasone - pharmacokinetics; Drug Carriers; Eye - metabolism; Fluorouracil - administration & dosage; Fluorouracil - chemistry; Fluorouracil - pharmacokinetics; General pharmacology; Glaucoma filtering surgery; Hydrogen-Ion Concentration; In vitro release; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Poly(ortho ester); Polymers - administration & dosage; Polymers - pharmacokinetics; Rabbits; Solubility; Glaucoma filtering surgery; Dexamethasone; 5-Fluorouracil; Bioerodible polymers; Capillary electrophoresis; Poly(ortho ester); In vitro release; Biocompatibility; Biodegradation; Postoperative; Corticosteroid; Pharmaceutical technology; Control release polymer; Toxicity; Fluoropyrimidine derivatives; Antiinflammatory agent; Ester polymer; Drug carrier; In vitro; Subconjonctival; Ethylene oxide polymer; Eye; Eye disease; Glaucoma (eye); Surgery; Pyrimidine derivatives; Antimitotic; Release; Fluorouracil
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/S0939-6411(00)00107-7

A viscous hydrophobic poly(ortho ester) (POE) has been developed as a biocompatible, biodegradable sustained release system for selected cases of glaucoma filtering surgery. Dexamethasone and 5-fluorouracil (5-FU) are frequently administered together post-operatively, for their anti-fibroblastic and anti-inflammatory properties, respectively. A combined sustained release of both drugs could be advantageously used. Drug release kinetics were studied using specially designed thermostated cells. Subconjunctival tolerance was evaluated on New Zealand albino rabbits by clinical evaluation. Due to its basicity, the addition of dexamethasone sodium phosphate (DEX-P) stabilized the polymer and prolonged 5-FU in vitro release from 2 to 4 days. Both therapeutic agents were released concomitantly, according to a linear profile. The presence of 5-FU only slightly affected the overall subconjunctival tolerance of POE in rabbits, whereas the addition of DEX-P markedly improved POE tolerance by reducing the hyperemia of the conjunctiva to a minimal grade.