Quality by design coupled with near infrared in formulation of transdermal glimepiride liposomal films

Abstract

This study is aimed at developing glimepiride (GMD) liposomal films using quality by design (QbD) and process analytical technology (PAT) principles. Risk analysis and Plackett-Burman design were utilized to evaluate formulation variables in two paths. Internal path included liposomal parameters (phosphatidylserine, cholesterol and drug concentrations, and pH of hydration medium). External path constituted films parameters, namely, polymer, plasticizer, and permeation enhancer percentages. As a PAT tool, near infrared (NIR)-based chemometric analysis was used in quantifying GMD contents. Liposomal formulations showed maximum GMD entrapment capacity of 41.9% with vesicular size of 0.51 μm at phospholipid to cholesterol to drug weight ratio of 2:1:0.8. Its transdermal films showed elongation ratio of 75%, folding endurance of 700-fold, 16.6% and 26.8% drug release after 1 and 12 h, respectively. Moreover, 3D response spaces for GMD entrapment and release characteristics were established. Regarding NIR analysis, partial-least-square regression model was accurate in quantifying drug content as indicated by the low root-mean-squared error of calibrations and prediction of 0.031 and 0.032, and bias values of 0.0015 and 0.0021, respectively. In conclusion, this study highlights the level of understanding that can be accomplished through a well-designed research based on QbD and PAT paradigms.

Keywords: Formulation; Infrared spectroscopy; NIR; Percutaneous; Placket-Burmann design; Transdermal drug delivery; glimepiride; liposomes; transdermal film.