Melt Extrusion and Spray Drying of Carbamazepine and Dipyridamole with Polyvinylpyrrolidone/Vinyl Acetate Copolymers

Abstract

Aim: Carbamazepine and dipyridamole are class II compounds (BCS) whose oral bioavailability is limited by poor solubility. The use of glass solutions to improve the bioavailability of this class of compound has been an area of research for a number of years. The influence of polymer parameters (T_g, hydrophilicity, solubility parameter, and ability to hydrogen bond) on glass solution properties is investigated. Methods: Carbamazepine and dipyridamole glass solutions are prepared with PVP/VA 64 and PVP/VA 37 by spray drying and melt extrusion. The products are then characterized by XRPD, thermal, and spectroscopic methods. Yield, physical stability, and dissolution profiles are also assessed.

Results: The properties of the polymer greatly influenced the ability to produce glass solutions. With decreases in T_g and hydrophilicity, melt extrusion became the more viable of the two preparative techniques. Although glass solutions were successfully prepared, the greater the difference in component solubility parameter, the less physically stable the formulation.

Conclusion: Consideration must be given to the characteristics of the polymer when selecting for glass solution formulation. Although a number of process parameters can be varied for melt extrusion and spray drying, their ability to overcome fundamental differences in the physical parameters discussed is limited.

Keywords:

• melt extrusion
• spray drying
• carbamazepine
• dipyridamole
• PVP/VA copolymer and physical stability

Notes

¹pH 6.8 buffer: 20 L prepared by addition of 10 L of Na₂HPO₄.2H₂O 17.8 g/L to 10 L of NaH₂PO₄.H₂O 13.8 g/L. pH was confirmed using a pH meter.

²During cyclic DSC analysis the maximum temperature of 100 °C was significantly lower than the temperature at which an onset of recrystallisation was observed.