Melt extrusion and spray drying of carbamazepine and dipyridamole with polyvinylpyrrolidone/vinyl acetate copolymers.
OBJECTIVE
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 (Tg, 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 Tg 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.


CONCLUSIONS
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.
Patterson
James E
JE
School of Pharmacy, University of Otago, Dunedin, New Zealand.
James
Michael B
MB
Forster
Angus H
AH
Rades
Thomas
T
D002220:Carbamazepine / Q000008:administration & dosage / Q000737:chemistry*; D004176:Dipyridamole / Q000008:administration & dosage / Q000737:chemistry*; D004355:Drug Stability; D011759:Pyrrolidines / Q000737:chemistry*; D012995:Solubility; D013678:Technology, Pharmaceutical; D014753:Vinyl Compounds / Q000737:chemistry*
D011759:Pyrrolidines; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); D002220:Carbamazepine; D004176:Dipyridamole