Abstract

QUALITY BY DESIGN: A SYSTEMATIC APPROACH USING AN ADVANCED STATISTICAL TOOL TO OPTIMIZATION OF NIOSOMES PREPARATION FOR THE TOPICAL DELIVERY

Parinbhai Shah, Benjamin Goodyear, Anika Haq, Vinam Puri and Bozena Michniak-Kohn*

ABSTRACT

QbD is a systematic approach that may be used to improve product quality, process understanding, and supporting adequate regulatory compliance for vehicle-based drug delivery systems commonly used in the pharmaceutical industry. The purpose of this investigation was to optimize critical material attributes & critical process parameters to effectively develop a niosomal drug delivery system for use with the topical application of desoximetasone. Formulation variables considered were based on previous research of niosome CMAs (surfactant & cholesterol concentrations), and CPPs (mixing time, mixing speed, & organic phase addition rate) variables. An extensive 25 factorial design was created using JMP® statistical software better to understand the effects of these parameters on niosome formulations. Experiments were systematically conducted to develop an in-silico profile predictor using the fit model and 3D surface plots. Various profile predictions were generated, and best fit model regression lines were selected to validate the niosome QTPP. An optimized formulation with 450 nm particle size and a 90% entrapment efficiency was obtained using a drug, surfactant, and cholesterol ratio (1:2:1) with an external phase temperature of 65°C, internal and external phase volume of 10 and 20 mL respectively, mixing parameters 650 rpm and 50 minutes and addition rate of 0.5 mL/min. By selecting specified CMAs and CPPs, optimized niosome vesicles containing desoximetasone was achieved successfully.

Keywords: Quality by Design (QbD), JMP® statistical software, Critical Material Attributes and Critical Process Parameters, Desoximetasone, Controlled drug delivery, Niosome, Allergic reactions, Topical drug delivery, Psoriasis, Eczema.