Formulation and Quality – Chemical
2019 PharmSci 360
Drug-in-adhesive TDS are designed to provide a controlled rate of drug delivery across human skin to elicit a desired pharmacologic effect. Permeation of drug substances from a TDS across the skin is mostly driven by the concentration gradient between the adhesive matrix and skin. To achieve a sustained rate of drug delivery over the period of intended application, TDS are usually formulated with drug concentration that is close to the saturation solubility in the adhesive matrix. This strategy helps minimize the surface area of the TDS, but it increases the risk of drug recrystallization over the product life cycle and shelf life. Visible crystals in a TDS can also undermine patient confidence in the quality of TDS. More importantly, recrystallization decreases the soluble amount of drug in TDS, which may decrease the rate of drug delivery and affect the drug product’s efficacy and physical performance. There have been several reports of drug recrystallization in TDS which led to their recall from the market such as Neupro® and Duragesic®. This presentation will focus on understanding the effects of drug recrystallization on drug release and permeation kinetics, as well as TDS physical characteristics. Moreover, various methodologies such as Raman mapping and X-ray diffractions will be discussed as tools that may be used to unveil the identity of crystals formed during development and aging of various TDS formulations. The regulatory considerations for assessing and mitigating the risk of drug recrystallization in TDS will be also discussed.