DESIGN SPACE EVALUATION OF FORMULATION AND PROCESS VARIABLES OF REPAGLINIDE TRANSDERMAL THERAPEUTIC SYSTEM

Repaglinide, a blood-glucose-lowering drug, has low oral bioavailability (56 %) due to first-pass metabolism and shorter half-life (~1 hour) lead to frequent dosing to control blood glucose level. Repaglinide Transdermal Therapeutic System (TTS) was prepared to provide continuous drug delivery for a prolonged period of time. Factors affecting critical quality attributes (CQA) of Repaglinide TTS are optimization of drug load in the adhesive matrix, selection of design, selection of permeation enhancer, matrix thickness, optimization adhesive characteristics, and optimization of delivery rate for a prolonged period of the time. In this research, the impact of critical material attributes (CMA), for example, the concentration of API and permeation enhancers, were studied on CQA like drug delivery and adhesive performance of the product using optimal full factorial design. Moreover, critical process parameters (CPP) were identified using the response surface method, and the impact of identified CPP (drying temperature) on CQA (residual solvents) was evaluated. The results of the design of the experiments study indicate a significant impact of API and permeation enhancer concentration on drug delivery along with mixed impacts on adhesion characteristics. A statistical model was determined based on the relationship between CMA, CPP, and CQA for predictability of the results in design space, and further, this model was validated based on % prediction error. The skin flux results show that Repaglinide TTS can provide the sustain drug delivery over the time period of 72 h.