Effect of storage on the dissolution rate of a fast-dissolving perphenazine/β-cyclodextrin complex.

Objective: In general, the chemical and physical stability of amorphous cyclodextrin complexes and how storage affects their dissolution rate have not been widely reported. The aim of this study was to evaluate the solid-state stability of a fast-dissolving perphenazine/β-cyclodextrin (β-CD) complex, which has been found to be well absorbed after sublingual administration to rabbits. In addition, the dissolution rate of plain β-CD in crystalline and amorphous forms was determined.

Methods: The amorphous perphenazine/β-CD complex powders were prepared by spray-drying and freeze-drying, and their stability was examined after storage at 40°C, 75% relative humidity (RH) or at room temperature, 60% RH for up to 82 days.

Key Findings: Perphenazine was found to be chemically stable in all samples. The dissolution rate of perphenazine remained practically unchanged at both storage conditions, although partial crystallization was observed in both spray-dried and freeze-dried samples at 40°C, 75% RH. Interestingly, it was also observed that the dissolution rates of crystalline and amorphous β-CD were similar.

Conclusion: The results suggest that CD complexation may represent a suitable alternative for preparing intraorally dissolving formulations because the fast dissolution rate of the drug was maintained even though changes in the crystal structure were observed during storage.