Design And Evaluation Of Ophthalmic Drug Delivery System Of Quinolone

As one of the important fields of controlled release, ophthalmic drug delivery has received extensive interests during the last two decades. The sensitivity and protection mechanisms of the eye promote more effective drug delivery systems with better compliancy to be developed, however, the applications of numerous pharmaceutical methods are limited simultaneously, which presents great challenge in designing ophthalmic dosage forms. In this dissertation, enoxacin (ENX) and gatifloxacin (GAT) were selected as model drugs, then an ophthalmic sustain-released gel of ENX and an ion-activated in situ gelling ophthalmic drug delivery system for GAT were developed and evaluated in vitro and in vivo, respectively. Seven main sections were included in this paper:1, The study on the solubilities and partition coefficients of drugsThe results showed that the solubilities of ENX and GAT were both dependent on pH value, and the partition coefficients were relatively low, which suggested the rate-limiting barrier was corneal epithelium. In order to increase the transcorneal influx of both drugs, penetration enhancers were needed to employ.2, The study on ophthalmic sustain-released gel of ENX? The permeability of ENX across isolated rabbit cornea was measured using in vitro method under various penetration enhancers. The diffusion behaviors of ENX across isolated rabbit cornea possessed zero-order kinetic characteristic. An apparent permeation coefficient of 1.795×10^-6 cm·s^-1 was found without enhancers. 1% poloxamer (F68) and 2% HP-β-CD improved the apparent permeability of ENX as much as 1.65 and 2.05, respectively. However, 0.05%Azone and 0.5%EDTA did not improve the apparent permeability of ENX. When the concentrations of HP-β-CD varied from 2% to 4%, the apparent permeation coefficient of ENX was increased 2.58-fold, but further increasing HP-β-CD concentration to 12% led to lower the P_app value of ENX. All enhancers did not significantly change the transcorneal lag time of ENX. The irritancy of poloxamer and Azone was observed.? The results of in vitro release studies showed that the ENX gel based 3% HPMC K4M and 3%HPMC F4M povided sustained release of the drug over an 8-h period in vitro.Diffusion area has significantly effect on drug release, and pH value of medium and rotation rate have effcet on drug release.However, the diffusion shield has no effect on drug release. The P_app value of the preparation based on 3% HPMC F4M was 1.34-fold of conventional eye drops of ENX. The results suggested that the compatibility between the...