Formulation and characterization of clay based film as oculardexamethasone delivery system

Abstract

The physiological barrier and protective nature of eye hinders the delivery of newlinesignificant amount of drug. Modified formulation could be delivered the medication to newlinethe target site of eye for longer time and provided better therapeutic efficacy, compared newlinewith conventional formulation. Ocular inflammation is effectively treated by potent newlineocular corticosteroid. Dexamethasone is glucocorticosteroid used for inflammation, newlineconjunctivitis, keratitis. Drugs can deliver over long time by introducing any material, newlinewhich can extend the retention and release to target site. The release of drug from matrix newlineis related to the swelling of that matrix. The objective of this study is to evaluate the newlinedexamethasone film containing kaolin for ocular inflammation treatment. The newlinedexamethasone film has been evaluated by swelling, in vitro release and ex vivo newlinepermeation as a kaolin content function and viscosity of hydroxypropyl methylcellulose newlinepolymer. Kaolin has ability to adhere to mucosa and can protect eye by absorbing newlineviruses, toxins, and bacteria.Swelling of hydroxypropyl methylcellulose matrix with newlinevaried kaolin studied as the measurement of hydration of matrix. Peleg and lag phase newlinemodel were utilized to understand the swelling kinetics of matrix. Furthermore, these newlinemodels were modified to evaluate the swelling process. Swelling of matrix was newlinecharacterized by the parameter such as swelling equilibrium,pelegcapacity constant, newlinepeleg rate constant. Permeation of drug through cornea studied byHiguchi and newlineKorsmeyer-Peppas model. Corneal permeation also described by measuring the newlinepermeation coefficient and flux. All film also characterized by FTIR, Differential newlinescanning electrometry, scanning electron microscopy, X-ray diffraction study. The newlinecorrelation between in vitro release and exvivo permeation was established to investigate newlinefurther corneal permeation. newlineThe prepared dexamethasone film with kaolin possessed adequate flexibility, newlineopacity and uniform drug content. The successful incorporation of dexamethasone in newlinefilm and interaction between dexamethasone and kaolin has been demonstrated in FTIR newlinespectra. In DSC thermogram, the disappearance of melting endotherm indicated that the newlinedrug in films possessed partial amorphization. X-ray diffraction pattern suggested the newlinereduce order of crystal lattice. Swelling of film was decreased with increasing kaolin newlinecontent and with higher viscosity HPMC. Erosion was inhibited due to presence of newlinexvi newlinekaolin in film. Peppas model described the swelling mechanism of film with kaolin as newlinethe diffusion controlled swelling. The diffusion coefficient was increased with increasing newlinekaolin content in films and with higher viscosity HPMC. The fitting of swelling with newlinemodified lag phase model was confirmed by small RMSE value and high R2 newlinevalue. The newlineobtained Swelling equilibrium value from modified lag phase model represented newlinesimilarity with experimental swelling equilibrium value. The increased peleg rate newlineconstant has described that the initial water absorption rate was decreased with higher newlinekaolin content in film.In vitro release study revealed that the film with kaolin have newlineability to extend the dexamethasone release up to 6 h without burst effect. Corneal newlinepermeation also extended more than 6 h. The significant difference in permeation newlinecoefficient of films with varied kaolin content was confirmed by the ANOVA (one way) newlinefollowed by Dunnett s test. The prepared film reduced the carrageenan induced ocular newlineinflammation in rabbit eye within 2 h. The in silico molecular docking study confirmed newlinethe interaction of (Dexamethasone-kaolin)-HPMC with higher negative binding energy newlinevalue. newline newline