Designing of a Thermosensitive Chitosan/Poloxamer In Situ Gel for Ocular Delivery of Ciprofloxacin

Abstract

To increase the low bioavailability and short ocular residence time of ciprofloxacin eye drops, aqueous solutions of drug in chitosan/ Pluronic (poloxamer) were prepared to identify suitable compositions with regard to gel forming properties and drug release behavior. Mixtures of solutions of Pluronic (10-25% w/w) with chitosan (0.1-0.3% w/w) of different molecular weights (Mw) were prepared. Ciprofloxacin release was determined using a membraneless dissolution model in artificial tear solution up to 8 hours and the samples were analyzed spectrophotometrically at 272.4nm. The rheological behavior of solutions in response to dilution or temperature changes and also the phase change temperature (PCT) were determined using a Cup & Bob viscometer. Antimicrobial effect of the solutions was studied in nutrient agar in comparison to marketed solutions of ciprofloxacin using Pseudomonas aueroginosa and Staphylococcus aureus by the agar diffusion test using the cup-plate technique. The formulation consisted of 15% Pluronic and 0.1% low Mw chitosan, with the highest release efficiency (46.61 ± 0.41%) and an acceptable mean release time (1.94 ± 0.27 hr), is suggested as a suitable ophthalmic preparation for sustained release of ciprofloxacin. This in situ gel released the drug by a Higuchi model and Fickian mechanism. It was liquid in non-physiologic conditions (pH 4 and 25ºC) and transferred to the gel form upon physiologic conditions (pH 7.4 and 37ºC). The PCT of this in situ gel did not change upon dilution and the zone of inhibition of the growth of both studied bacteria was significantly greater for it than the marketed eye drop of ciprofloxacin.

Comparative topical delivery of antifungal drug croconazole using liposome and micro-emulsion-based gel formulations

“…According to this equation, if n 0.45, the release of drug follows Fickian mechanism, if 0.5 n 0.8, the release of drug is nonFickian and if 0.8 n 1, a zero-order mechanism is governing the drug release mechanism from the gel (Varshosaz et al, 2008).…”

Newer Trends in In Situ Gelling Systems for Controlled Ocular Drug Delivery

“…It was liquid in non-physiologic conditions (pH 4.0 and 25ºC) and transformed in to the gel form in physiologic conditions (pH 7.4 and 37ºC). The phase transition temperature of this in situ gel did not change upon dilution and the zone of inhibition of Pseudomonas aeruginosa and Staphylococcus aureus was significantly greater for the formulation as compared to the marketed eye drop formulation of ciprofloxacin in the agar diffusion test [12].…”

“…The suitable compositions of chitosan-PluronicF 127 solution to achieve good gel forming properties and drug release behavior for enhancing the low bioavailability and ocular residence time of ciprofloxacin has been investigated by Varshosaz et al [12]. In this investigation, various compositions of Pluronic F127 (10-25% w/w) with different molecular weights chitosan (0.1-0.3% w/w) solutions were prepared.…”

“…A wide variety of drug molecules and materials of therapeutic advantages such as antibiotics (Ofloxacin, Ciprofloxacin, Gatifloxacin), beta blockers (Timolol, Carteolol), NSAIDs (Ketorolac Tromethamine, Indomethacin), Pilocarpine hydrochloride, Puerarin, Recombinant rhEGF, Antivirals (Acyclovir) has been delivered through in situ gelling systems, which shows the importance of in situ gelling formulations as the future drug delivery systems [7][8][9][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25].…”

Contemporary Trends in Novel Ophthalmic Drug Delivery System: An Overview

“…The rheological behavior, phase change temperature (PCT) and antimicrobial effect of the solutions was studied. The authors found that this in situ gel released the drug by a Higuchi model and Fickian mechanism, it was liquid in non-physiologic conditions and transferred to the gel form upon physiologic conditions and they concluded that the PCT of this in situ gel did not change upon dilution and the zone of inhibition of the growth of both studied bacteria was significantly greater for it than the marketed eye drop of ciprofloxacin [38].…”