RELEASE ENHANCEMENT OF MELOXICAM FROM TRANSDERMAL GEL THROUGH CYCLODEXTRIN COMPLEXATIONAbstract
The purpose of the study was to determine the in vitro as well in vivo efficiencies of 1% carbopol hydrogel different preparations containing the meloxicam, a cyclooxygenase-2 inhibitor anti-inflammatory drug with b-cyclodextrin. The release of plain drug was then compared with release of from trans dermal gel containing physical mixture of drug and b-cyclodextrin, inclusion complex of drug and b-cyclodextrin obtained by kneading method and in situ complex of drug and b-cyclodextrin obtained by reacting the drug and b-cyclodextrin within the gel. All solid inclusion complex abstained were then characterized by x-ray diffractrometry, infrared spectroscopy, differential scanning colorimetry and scanning electron microscopy, where as the in situ complex formation was evidenced only by release and permeation studies. Although many other derivative of cyclodextrins such as hydroxy propyl-b-cyclodextrin and methylated-b-cyclodextrin are better skin permeating enhancers but in this study b-cyclodextrin was employed because of ease of availability and low cost. Solid inclusion complex was prepared by kneading method. Gel formulations were prepared by incorporating pure drug, physical mixture, inclusion complex and separately drug and b-cyclodextrin dispersed in propylene glycol (to get in situ complex) to the gel base. Prepared gels were subjected to physical evaluation for its viscosity, pH and drug content. In vitro drug release and in vitro drug permeation experiments were carried out on Franz diffusion cell using cellophane membrane and human cadaver skin respectively. Selected formulations were evaluated for anti-inflammatory activity using the carrageenan-induced paw oedema in rats. Differential scanning colorimetry and infrared spectroscopy studies indicate the complexation where as x-ray diffractrometry studies indicate conversion of crystalline drug to porous, spherical and fluppy structures. The release rates when compared were found to be highest with gel containing inclusion complex than the gels containing pure drug, physical mixture and the in situ complex. A lag period was observed with all formulations. Physical stability was performed by freeze thaw cycling. The complex containing in situ complex was more stable. The overall data suggest that the prepared hydrogel of meloxicam is highly efficient transdermal vehicle for the delivery of the drug at the site of action.