Control of drug crystallization in transdermal matrix system

Supersaturation of a drug in a transdermal system is often desirable in order to deliver a target therapeutic dose into the body. Preventing drug crystallization during storage is of importance for such a metastable system. In this study, the following additives were examined under various conditions for transdermal systems: polyvinylpyrrolidone (PVP) and its derivatives; dextrin derivatives; polyethylene glycol (PEG); polypropylene glycol (PPG); mannitol; and glycerin. Norethindrone acetate (NETA) was used as the model drug. The effects of several variables, such as storage temperature and drug loading, on crystallization were also investigated. PVP was found to be the most effective crystallization inhibitor. A lower storage temperature, i.e. 4 degrees C, could significantly increase the induction time of drug crystallization in monolithic matrix transdermal systems.