Quality by Design-Based Optimization of Silymarin–Pioglitazone Nanoemulsion for Enhanced Topical Delivery

Abstract

The primary objective of the present study was to develop and optimize a nanoemulsion formulation of silymarin and pioglitazone for enhanced topical delivery of antidiabetic effect using Quality by Design (QbD) approach. Both drugs exhibited poor aqueous solubility and low bioavailability in water and also had low bioavailability, which required the advanced development of a nanocarrier system that could enhance drug permeation and therapeutic efficacy. Organoleptic evaluation, solubility analysis, Fourier-transform infrared spectroscopy (FTIR) were conducted as preformulation studies to evaluate the physical properties and compatibility of the drug. Capryol 90 was optimized as the oil phase, and Tween 80 and Transcutol P as the surfactant and co-surfactant, respectively. The pseudo-ternary phase diagrams were prepared with various Smix ratios to determine the nanoemulsion region and 2:1 Smix ratio showed the best formulation of nanoemulsion. Central Composite Design (CCD) based QbD approach was used to optimize formulation variables and oil concentration, Smix concentration were selected as the independent variables and particle size, polydispersity index (PDI), and drug loading were selected as dependent response. Optimized nanoemulsion had nanosized globules, narrow size distribution and high drug loading efficiency. Developed models were found to be appropriate and significant through statistical analysis. Further, transmission electron microscopy (TEM) studies showed spherical and uniform nano-sized droplets. The optimized formulation demonstrated excellent physicochemical stability in terms of physicochemical stability and as formulation characteristics for topical application. In conclusion, the developed nanoemulsion system of silymarin and pioglitazone showed great potential to be an advanced nanocarrier system for more efficient topical antidiabetic treatment.