Pharmaceutical Science: New Insights and Developments Vol. 11

Transdermal patches are user-friendly and widely accepted medicated adhesive systems that deliver drugs through the skin for controlled systemic effects. The widely used approach for improving transdermal drug delivery employs penetration enhancers, which can often cause skin irritation and toxicity. Solid lipid nanoparticles have emerged as promising carriers to improve skin delivery of active compounds. The objective of the research work is to develop and evaluate the Solid Lipid Nanoparticles (SLNs) loaded matrix type transdermal patch of Nisoldipine (NSD). SLN formulations were developed and evaluated for particle size, zeta potential, polydispersibility index, drug content, and entrapment efficiency. N-D4 formulation with Dynasan 114 lipid and 1.5% of poloxamer was optimised as it was effective in producing physically stable SLNs with a zeta potential value of -23.1±7.01mv and small size SLNs of 202.4±4.26nm with entrapment efficiency of 98.2%. N-D4 formulation was freeze-dried and incorporated into a transdermal patch.SEM analysis showed non-aggregated spherical particles. The physicochemical interaction between Nisoldipine and polymer was examined by DSC (Differential Scanning Calorimetry) and FTIR (Fourier Transform Infrared Spectroscopy). Prepared patches were measured for thickness, uniformity of weight, folding endurance, moisture content, and moisture absorption. The in-vitro and ex-vivo permeation of Nisoldipine from the patches was studied by Franz diffusion cells. An in vivo bioavailability study was performed using male Wistar rats for optimised formulation N6 and compared with the reference tablet (Sular). N6 formulation patch containing 600mg HPMC E15 and 8% citral as permeation enhancer showed 96.5% of drug release and higher flux (15.8 µg/cm²/h) when compared to theoretical flux (12.36 µg/cm²/h) with 2.17 enhancement ratio (ER). Citral increases the drug partition coefficient into tissue by modifying the solvent nature of the stratum corneum. Relative bioavailability of the test formulation with respect to the market formulation was considered to be 2.52, and an increase in half-life for the patch (34.65h) compared to the oral formulation (13.33h) indicates sustained drug release from patches compared to the oral formulation. The SLN-loaded transdermal patches of Nisoldipine were developed successfully with a considerable increase in bioavailability of the test formulation (N6) when compared to the marketed formulation. The increase may be attributed to the avoidance of first-pass metabolism of Nisoldipine, which occurs through oral administration.