Gel-forming erodible inserts for ocular controlled delivery of ofloxacin

• Published in: International journal of pharmaceutics 2001-03, Vol.215 (1), p.101-111
• Main Authors: Di Colo, G, Burgalassi, S, Chetoni, P, Fiaschi, M.P, Zambito, Y, Saettone, M.F
• Format: Article
• Language: English
• Subjects: Animals; Anti-Infective Agents - administration & dosage; Anti-Infective Agents - chemistry; Anti-Infective Agents - pharmacokinetics; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Aqueous Humor - metabolism; Biological and medical sciences; Biological Availability; Controlled drug delivery; Delayed-Action Preparations; Excipients; Eye - drug effects; Eye - metabolism; General pharmacology; Male; Materials Testing; Medical sciences; Mucoadhesive polymer; Ocular bioavailability; Ocular drug delivery; Ocular insert; Ofloxacin; Ofloxacin - administration & dosage; Ofloxacin - chemistry; Ofloxacin - pharmacokinetics; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Poly(ethylene oxide); Polyethylene Glycols; Rabbits; Solubility
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(00)00671-2

A new application of high molecular weight (400 kDa) linear poly(ethylene oxide) (PEO) in gel-forming erodible inserts for ocular controlled delivery of ofloxacin (OFX) has been tested in vitro and in vivo. Inserts of 6 mm diameter, 20 mg weight, medicated with 0.3 mg OFX, were prepared by powder compression. The in vitro drug release from inserts was mainly controlled by insert erosion. The erosion time scale was varied by compounding PEO with Eudragit L100 (EUD) 17% neutralized (EUDNa17) or 71% neutralized (EUDNa71). The insert erosion rate depended on the strength of interpolymer interactions in the compounds, and on the hydrophilic-hydrophobic balance of compounds. Immediately after application in the lower conjunctival sac of the rabbit eyes, the inserts based on plain PEO, PEO–EUDNa17 or PEO–EUDNa71 formed mucoadhesive gels, well tolerated by the animals; then the gels spread over the corneal surface and eroded. The gel residence time in the precorneal area was in the order PEO–EUDNa71MIC) were strikingly increased by plain PEO inserts with respect to commercial eyedrops (5.25±0.56 vs. 1.39±0.05 μg ml −1; 693.6 vs. 62.7 μg ml −1 min; and 290 vs. 148 min, respectively). Bioavailability increase has been ascribed to PEO mucoadhesion and/or increased tear fluid viscosity.