| The objective of this study is to investigate the feasibility of delivering recombinant human (regular, hexameric) insulin from polymer matrices across the stratum corneum through thermally created micropores.; Transdermal patches of insulin gel and film were prepared using polymers (HPMC, HEC, PVA, and EVA), and diluents/osmolytes (mannitol, sorbitol, and sucrose). In vitro drug release studies were conducted using Franz diffusion cell. The effects of insulin concentration, polymer concentration, diluent, and diluents concentration on release profile of insulin were studied. The release rate of insulin from polymers increased linearly with increasing insulin and diluent concentration. Controlled release system of insulin could be developed using polymers and diluents.; For permeation studies, hairless rats (cannulated) were first anesthetized by isofluorane gas. A PassPort(TM) system device (Altea Therapeutics, GA) was used to create micropores on the abdominal skin of the rat. A patch or film with insulin formulation was applied over the microporated area. Factors affecting insulin delivery such as buffers, buffer concentration, formulation excipients, formulation parameters (concentration, film thickness), micropore density, and activator pulse length were investigated. Samples were analyzed for insulin concentration by a validated ELISA method as well as for glucose levels. Delivery of insulin through microporated skin can be modulated by controlling the concentration of insulin, polymer, and diluents in the film or changing patch thickness, micropore densities, and activator pulse length.; Insulin self association was studied at various concentrations, pH, temperatures, and in various excipients using dynamic light scattering (DLS), size exclusion chromatography (SEC), and gel electrophoresis (SDS-PAGE). Excipient compatibility studies were done using differential scanning calorimetry (DSC). Insulin formulation was found to be stable during formulation processing as well during the 24 hours of patch application period by light scattering, gel electrophoresis, size exclusion - HPLC, and Differential scanning calorimeter.; Lyophilized insulin formulation was stable during the 24 hours of patch application period. DSC data suggested that there was no interaction between insulin and excipients. |
