Design and development of buccoadhesive and transdermal systems of duloxetine hydrochloride inclusion complexes

Abstract

The work encompasses systematic development of inclusion complexes of duloxetine HCl (DLX) for enhanced bio performance in systemic circulation. Initially, analytical and bioanalytical method for the quantitative estimation of drug was developed employing HPLC. Further, bioanalytical method was established to carry out the in vivo pharmacokinetic studies on the optimized formulations. Varied inclusion complexes using freeze drying and spray drying methods for DLX, were developed. Various physicochemical attributes based on the outcomes of various protocols were analysed. Subsequently, factor screening studies were conducted, depending on the results and systematically optimized. Later, a blend of numeric (e.g., desirability function) and graphic (e.g., overlay plotting) optimum search procedures were employed to demarcate the optimum solution. The formulations developed as per prevailing hypothesized strategy were characterized for various CQAs like particle size, drug content, complexation efficiency and drug release profile. For ideal transdermal delivery, the optimized formulations were administered to animals employing the best suited route of administration. The pharmacodynamic performance was analyzed employing forced swim test and locomotor activity test. In vitro interaction of formulations with natural (i.e. Chitosan and Na alginate) and synthetic (i.e., HPMC) for better bio-adhesion was explored for investigating their sustaining and prolonged release potential and stability vis-à-vis the respective pure drug(s) forms. Further, the optimized formulations were tested on dermal fibroblast cells for their safety and uptake potential. In vivo studies carried out in mice employing well established protocol indicated significant improvement in bio-performance and biopharmaceutical attributes in systemic circulation vis-à-vis pure drugs. newline