The effect of storage time on the release profile of dexamethasone dipropionate from admixtures of steroid and heparinoid ointments

We examined the stability and release profiles of dexamethasone dipropionate (DDP) from admixtures by using an innovator ointment (Methaderm [IM]), two generic ointments (Promethasone [GP] and Mainvate [GM]), and a heparinoid ointment. The admixtures were prepared using a spatula and an ointment slab and were stored at room temperature. Microscopic and Fourier transform-Raman spectrometric analyses showed that crystallization of DDP in admixtures of IM after 1 week of storage occured. And DDP crystals in all admixtures of GP and GM were observed. DDP was not decomposed in the admixtures after storage. Cumulative DDP permeation across a silicone membrane in a 1-week storage sample of the IM system decreased with DDP crystallization and reached a plateau after 2 weeks. In the GP and GM systems, DDP permeation decreased after 1 week of storage and increased again after 2 and 4 weeks. Each admixture was separated into 3 phases (liquid, lower, and upper solid phases) by ultracentrifugation to determine the apparent solubility of DDP. The DDP contents in the upper solid phase of the IM admixtures at 1, 2, and 4 weeks were lower than that in the 0-week sample. No significant differences were observed in the DDP content between the liquid phases throughout the storage period. Therefore, the amount of DDP dissolved in the upper solid phase may influence DDP release from the IM admixtures. The GP and GM systems showed no significant differences in the apparent DDP solubility. These results indicate that the dispersion state of DDP in the tested admixtures may be altered with storage.