Formulation development for transdermal and intradermal delivery of pharmaceuticals and cosmeceuticals

Purpose. The broad aim of this research project was to develop patch or cosmetic formulations for transdermal or intradermal delivery of pharmaceuticals and cosmeceuticals.;Methods. Different therapeutic molecules including levonorgestrel (Levonorgestrel), captopril (Captopril), SMA-012, 4-ethoxy benzaldehyde, retinol and retinoic acid were used in the project. For patch studies, an acrylate adhesive (DuroTak-2516) and a silicone adhesive (BIO PSA) were selected. Drug-in-adhesive (DIA) patches were made for levonorgestrel and captopril using solvent evaporation method. Slide crystallization studies were performed to select the best crystallization inhibitor for both levonorgestrel and captopril. Patches were evaluated using in-vitro skin permeation studies across rat skin and characterized using release studies. Differential Scanning Calorimetry (DSC) studies were also performed and compared to slide crystallization studies for screening of crystallization inhibitors. Accelerated stability testing of DIA patches was done using the process of die cutting. Freezing conditions were tested to inhibit the process of crystallization and stabilize patches for longer periods. Lag time experimental model was developed to predict the saturation solubility of a drug in any adhesive.;Formulation optimization was done for the skin lightener, NYU-201, using in vitro skin permeation experiments through human skin. Skin irritation and efficacy testing of the optimized formulation were performed using three dimensional Epiderm™ and Melanoderm™ models. Long term stability of formulations of retinol and retinoic acid was tested at room temperature storage conditions.;Results and Conclusions. Slide crystallization study is an effective tool and can be used with DSC studies to predict crystallization inhibition potential of additives. Addition of polyvinylpyrrolidone in DIA patches enabled higher loadings of levonorgestrel and captopril but did not affect the skin permeation or release profiles of levonorgestrel or captopril as compared to saturated patches. Die cutting of patches and freezing storage conditions can be used to perform accelerated stability testing and to inhibit crystallization of drugs in DIA patches respectively. Lag time permeation experiments proved to be useful in predicting the saturation solubility of a drug in any adhesive.;NYU-201 (0.1 %) formulation was selected using in vitro skin permeation experiments. This formulation was also found to be non-irritant and effective in decreasing melanin in Epiderm and Melanoderm models respectively. Formulations of retinol and retinoic acid showed degradation and were not stable for long term storage.