Formulation and Evaluation of Hydroxypropyl and#946; Cyclodextrin based Fast Dissolving Oral Thin Films of Quercetin

Abstract

The purpose of the current work was to enhance the solubility of Quercetin (QUE) by developing inclusion complexes followed by developing them into fast dissolving films. QUE was found to be BCS class-4 molecule with desired cancer preventive activity but characterized by lower solubility and permeability. To overcome the issues associated with QUE, the current research was designed for the development of cyclodextrin based inclusion complexes loaded orally fast dissolving films (ICQF). Quality by design (QbD) based statistical approaches were employed using Design Expert software for the development and optimization of the formulations. newlineThe first step of the work focused on preparing ternary cyclodextrin inclusion complexes of QUE (ICQs) with tween-80 as surfactant employing quality by the design tool. The concentration of hydroxypropyl-and#946;-cyclodextrin, tween-80, and method of preparation were taken as critical process parameters and evaluated to get the final product with desired solubility and dissolution rate as the responses. The central composite design was used for the systemic development of ICQs. The % yield and drug content of the prepared ICQs were found to be greater than 90% and 98%, respectively. X-ray diffraction and differential scanning calorimetry results showed the QUE was converted into an amorphous form after the formulation of ICQs. Improved solubility and dissolution rate was observed for the prepared ICQs than pure drug. The design method was optimized, and design validation studies were also performed. All the factors significantly influenced both solubility and dissolution at p lt 0.05. Based on the suggested combinations by overlay plot of graphical optimization, a new formulation was developed and evaluated for solubility and dissolution, which were impressively increased from pure QUE. The solubility and dissolution rate constant of the optimized ICQs were found to be 0.746 mg/mL and 0.193 min-1 respectively. This optimized ICQ was taken for the development of the ICQFs. newline