A fast-disintegrating sublingual tablet (FDST) of epinephrine (Epi) for the treatment of anaphylaxis has been successfully developed and evaluated in vitro and in vivo. The formulation of Epi FDST was recently licensed for GMP product development and clinical testing. In this formulation, Epi microcrystals and nanocrystals were developed and used to enhance drug permeation and absorption from the sublingual route using our developed taste-masked FDST platform.
We hypothesized that the evaluation and understanding of the effect of the medium's pH in the sublingual cavity and various penetration enhancers on Epi permeability can result in further optimization of the FDST formulation in order to further reduce the required bioequivalent sublingual Epi dose. In addition, it would facilitate for the development of smaller Epi FDST dosage form or even alternative dosage forms for pediatric use.
The objectives of this proposal are to 1) evaluate the effect of pH of the diffusion medium on Epi permeation in order to understand how to better optimize FDST formulation and enhance Epi absorption; 2) evaluate the effect of various penetration enhancers on Epi permeation in order to understand the mechanism of Epi transport across the sublingual membrane, which would allow for enhancement of its absorption; and 3) evaluate various pharmaceutical excipients and their effect on enhancing the tablets' physical characteristics and Epi permeation by testing various excipients to optimize Epi FDST formulation and allow for the development of smaller Epi tablet size or alternate dosage form for pediatric patients.
The effect of the pH and penetration enhancers on the permeation of Epi will be evaluated using Franz's cells diffusion cells through an excised porcine sublingual membranes according to our previously developed and published methods. Epi FDST will be developed, manufactured, and tested using our previously developed and published techniques and quality control tests. Various excipients will be evaluated to optimize FDST formulation and Epi permeation in order to allow for the reduction of the tablet size for pediatric use. Samples will be quantitatively analyzed using High Performance Liquid Chromatography (HPLC) system equipped with ultraviolet detections according the USP method. Data will be statistically analyzed using NCSS statistical analysis software at a significance level of p<0.05.
Upon the completion of this project, the new optimized FDST formulation will not only have better physical properties but hopefully should allow for the reduction of the tablet size for pediatric population and the reduction of the required Epi dose through delivering Epi more efficiently through the sublingual route.