Development and Validation of a Novel Diffusion Chamber for In Vitro Permeability Testing of Topically Delivered Spray Formulations

Abstract

In vitro testing of pharmaceutical formulations is an integral part of development of new drugs and formulations. The use of in vitro tests, which have a better in vitro-in vivo correlation, allows for a more efficient transition from in vitro testing to animal studies. Current testing protocol ignores the method of application opting instead for one-size-fits-all testing. In the case of topical spray formulations this may result in ignoring physical changes to a formulation that occur during application. The purpose of this study was to develop a diffusion chamber which is capable of receiving a direct spray application onto a model membrane for the in vitro evaluation of the diffusion of agents from topical spray formulations. This diffusion chamber, as developed in this investigation was coined the Munt/Dash chamber, was validated using two model drugs, diclofenac sodium and lidocaine hydrochloride. Shed snake skin was used as a model for human stratum corneum in these studies. Paired in vitro diffusion studies were performed using commercial and lab generated formulas for each drug in both Munt/Dash and Franz diffusion chambers. Diffusion data from the Munt/Dash chamber was compared with Franz diffusion chambers and with literature data for in vivo topical permeability. For diclofenac sodium the Munt/Dash chamber showed steady state flux of 0.22±0.02 and 1.53±0.15 μg/cm2*hour for lab and commercial formulations respectively where Franz chambers showed flux of 1.23±0.04 and 0.96±0.08 μg/cm2*hour respectively for the same solutions. Significant (p>0.05) differences were observed in the permeability and steady state flux of diclofenac and lidocaine. The Munt/Dash chamber produced similar standard error to Franz chambers. Changes in the concentration of formula components due to drying and changes to the membrane due to submersion are likely sources for the observed differences. Comparisons with previously reported in vivo studies were inconclusive suggesting that further paired in vivo and in vitro studies would be required to determine if this device does improve the in vitro-in vivo correlation. This study is a first step in the improvement of the in vitro evaluation of topical sprays which will reduce development time and increase accuracy of early studies.