Mixture design approach for early stage formulation development of a transdermal delivery system.
Transdermal delivery systems (TDS) consisting of mixtures of adhesives also named multiple polymer adhesive systems are rarely found in the market and research has only been performed on a few of them. Following the principles of ICH Q8, a Design of Experiments (DOE) approach was selected for the formulation development. For evaluation of the statistical method of "mixture design", blends of silicon adhesive, acrylic adhesive, oleyl alcohol as a surfactant and ibuprofen as a model drug were considered to be combined at different concentrations. A randomized design of 16 runs with five replicates and five runs to estimate the lack of fit (LOF) was generated. Samples were tested for adhesion properties, stability of the wet mixes, solubility of the API in the matrix and appearance of the matrix. After performing an ANOVA with the results, response surfaces of tack, shear adhesion, extent of creaming, crystallization behavior, droplet size and droplet size range were derived as contour plots. It could be shown that crystal growth of ibuprofen correlates well with droplet size and droplet size range, where lowest values for crystallization were found with mixtures containing small droplets. However, it was observed that oleyl alcohol showed no positive effect on the miscibility of the polymers and no improvement of the solubility of ibuprofen in the mixtures. With a reasonable number of experiments, the development of a design space for a TDS via mixture design gave valuable information on the product as well as on the interactions of the components.
['Michaelis|M|M|', 'Leopold|C S|CS|']
D000268:Adhesiveness D000269:Adhesives D000279:Administration, Cutaneous D002626:Chemistry, Pharmaceutical D003460:Crystallization D016503:Drug Delivery Systems D005233:Fatty Alcohols D007052:Ibuprofen D011108:Polymers D012825:Silicon D012995:Solubility D013501:Surface-Active Agents D057968:Transdermal Patch
multiple polymer adhesive system ICH Q8 Design of experiments mixture experiment polymer blend quality by design transdermal patch