Scientific Publications by FDA Staff

J Pharm Sci 2020 Jul 20 [Epub ahead of print]

Evaluation of heat effects on fentanyl transdermal delivery systems using in vitro permeation and in vitro release methods.

Zhang Q, Murawsky M, LaCount TD, Hao J, Ghosh P, Raney SG, Kasting GB, Li SK

Experimental conditions that could impact the evaluation of heat effects on transdermal delivery systems (TDS) using an in vitro permeation test (IVPT) and in vitro release testing (IVRT) were examined. Fentanyl was the model TDS. IVPT was performed using Franz diffusion cell, heating lamp, and human skin with seven heat application regimens. IVRT setup was similar to IVPT, without using skin. Dissolution study was conducted in a modified dissolution chamber. The activation energy of skin permeation for fentanyl was determined using aqueous solution of fentanyl. In IVPT, the increase of temperature from 32°C to 42°C resulted in a 2-fold increase in flux for fentanyl TDS, consistent with the activation energy determined. The magnitude of flux increase was affected by the heat exposure onset time and duration: higher flux was observed when heat was applied earlier or following sustained heat application. Heat induced flux increases could not be observed when inadequate sampling time points were used, suggesting the importance of optimizing sampling time points. The IVRT results suggest that the heating-lamp method was not suitable for heat-effect evaluation. Drug release from TDS evaluated using IVRT was fast and the skin was the rate-limiting barrier for TDS fentanyl delivery under elevated temperature.