Characterization and in vitro and in vivo evaluation of cross-linked chitosan films as implant for controlled release of citalopram

Abstract

The aim of the present study is to develop cross-linked chitosan (CH) films that can release drug over an extended period of time and that too in a controlled manner. A solution of different percentages of CH, is prepared in 1% lactic acid, followed by addition of citalopram (CTP) and then reacted with increasing amounts of glutaraldehyde (GL) to obtain films with different cross-linking densities. Prepared films are characterized for their physical and mechanical properties. The films are then subjected to in vitro drug release studies using pH 7·4 phosphate buffer saline (PBS) as dissolution medium and cumulative amount of drug released is calculated. Kinetic analysis of drug release is performed using Power law model and Higuchi’s model. With increase in concentration of CH, water absorption capacity and mechanical strength are increased; whereas, water vapour permeability and elasticity of the films are decreased. The effect of cross-linking agent, GL, is such that with an increase in the amount of GL, water vapour permeability, water absorption capacity and elasticity of the films are decreased; whereas, mechanical strength increased to some extent and then decreased. In vitro release studies indicate that films containing 3% CH, cross-linked with 2–3% GL and films containing 4% CH, cross-linked 1% GL are able to sustain the drug release for a prolonged time along with releasing almost complete drug in a desired period. Out of these batches, films containing 3% CH, cross-linked with 2–3% GL are having sufficient strength, water vapour permeation, water absorption capacity and elongation at break for implantation purpose. The in vitro degradation studies and histopathological studies were carried out with a sample film (batch C3 as in table 1) in rabbit model. In vitro degradation study indicates that the films maintained their integrity for desired implantation. The histopathological studies under optical microscope indicates that on implanting, there is no evidence of any inflammation, any foreign body granuloma or any necrosis or hemorrhage. Tissue configuration remains unaltered after 30 days of implantation. So, it can be suggested that cross-linked CH films of above said composition can be used as implant for long term application in depression and related disorders.