Abstract:

Objective： To prepare felodipine/copovidone solid dispersions, which were made based on different preparation technologies. Insoluble felodipine was selected as the model drug in this research. This drug belonged to Biopharmaceutics Classification System Ⅱ (BCSⅡ) with insoluble property and good permeability across intestinal mucosa simultaneously. A comparative study was carried out for further investigating their corresponding pharmaceutical properties. Methods: Felodipine/copovidone solid dispersions were achieved by four methods including spray-drying method, microwave-induced fusion quench cooling method, freeze-drying method and co-precipitation method. These solid dispersions were produced based on corresponding processes that corresponded to these methods. Internal properties of co-povidone solid dispersions were analyzed by various approaches including scanning electron microscope (SEM), differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). The improvement on insoluble properties of felodipine by solid dispersions produced by different technologies was characterized by dissolution experiments based on dissolution instrument. Crystallization inhibition effect of polymers against drugs was studied by supersaturated experiments through determining the concentration value at different time points. Results: The internal drug was dispersed in amorphous form in solid dispersions produced by spray-drying, microwave method, microwave/quench-cooling method and co-precipitation method. Freeze-drying method resulted in a form of crystal in felodipine/copovidone solid dispersions. Compared with other technologies, microwave-induced quench cooling method could significantly improve the dissolution of insoluble drug felodipine (P<0.05). The dissolution concentration reached approximately 4.65 mg/L at 60 min time point. Copovidone could inhibit or retard the crystallization of felodipine in a supersaturated state. In the solution pre-dissolved with maximum copoyidone po-lymer, the minimum crystallization rate of supersaturated felodipine was observed at 240 min time point. The value of crystallization rate was 0.19 mg/(L·min). Conclusion: The study is helpful to understand and clarify the internal properties of solid dispersions obtained by different technologies. The research also provides beneficial consultation for the choice of technology in practical production of drug-polymer solid dispersions.

Key words: Felodipine, Drug preparation, Solubility, Solid dispersions