Nanosuspension-Based Gel of Ketoprofen for Transdermal Delivery: Preparation, In Vitro and In Vivo Penetration Evaluation

This study aimed to prepare ketoprofen nanosuspension-based gel and evaluate in vitro and in vivo penetration compared with general gel. Ketoprofen nanosuspensions were successfully prepared by precipitation combined high pressure homogenization (PCH) method. Central composite experimental design was applied to optimize ketoprofen nanosuspensions prescription. Three formulation variables: content of F68 (X-1), content of soybean lecithin (X-2) and content of ketoprofen (X-3) were included in the design. The systems were evaluated for mean particle size (Y-1) and polydispersity index (Y-2). The optimized ketoprofen nanosuspensions were assessed for particle size, size distribution, morphology and crystallinity. The results demonstrated that ketoprofen nanosuspensions with a mean particle size of 46.71 +/- 6.89 nm and a polydispersity index of 0.137 were obtained. The result of differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRPD) showed that crystalline of ketoprofen was transformed into the amorphous form during the nanosuspension preparation procedure. Compared to ketoprofen gel, the optimized ketoprofen nanosuspension- based gel indicated the higher cumulative amount of permeated through mouse skin and skin retention amount after 24 h in vitro penetration experiments. The results from in vivo penetration experiments highlighted the nanosuspension capability to favor ketoprofen retention in the skin and muscle while minimizing transdermal delivery of the drug, responsible of its side effects. Overall, this work had attested the high potentiality of nanosuspensions-based gel in dermal drug delivery of ketoprofen.