Compression Effects on the Phase Behaviour of Miconazole-Poly (1-Vinylpyrrolidone-Co-Vinyl Acetate) Solid Dispersions-Role of Pressure, Dwell Time, and Preparation Method.
Compression of miconazole-poly (1-vinylpyrrolidone-co-vinyl acetate) (PVPVA64) solid dispersions prepared by spray drying and hot-melt extrusion was performed to gain insights into effect of compression pressure, dwell time, and preparation method on compression-dependent phase behavior. The solid dispersions prepared by spray drying were initially phase-separated showing two glass transition temperature (Tg), whereas the extruded samples showed one single Tg indicating better mixing. Compression caused mixing of spray-dried solid dispersions at high compression pressures and especially high dwell times. The extruded systems showed no statistically significant differences. However, physical mixtures made up from extruded samples containing 20% and 40% of active pharmaceutical ingredient underwent mixing upon compression. Coincidence Doppler measurements were performed to quantify the free volume of PVPVA64 which is a major contributor to the free volume in the solid dispersion matrix. A small but significant difference was found between the open free volume of the pure polymer subjected to varied manufacturing processes. Compression-induced plastic deformation and plastic flow enhances molecular mobility leading to mixing of different domains in solid dispersions. Different manufacturing methods may result in products with similar free volume, thereby showing similar molecular mobility.
Drug Delivery and Disposition, KU Leuven, Leuven, Belgium.
Abhishek
A
Singh
Drug Delivery and Disposition, KU Leuven, Leuven, Belgium.
Cathérine
C
De Bisschop
Faculty of Applied Physics, Delft University of Technology, Delft, The Netherlands.
Henk
H
Schut
Department of Metallurgy and Materials Engineering, KU Leuven, Leuven, Belgium.
Jan
J
Van Humbeeck
Drug Delivery and Disposition, KU Leuven, Leuven, Belgium.
Guy
G
Van Den Mooter
D002152:Calorimetry, Differential Scanning; D003890:Desiccation / Q000379:methods; D004339:Drug Compounding / Q000379:methods*; D005079:Excipients / Q000737:chemistry*; D008825:Miconazole / Q000737:chemistry; D011208:Powders; D011312:Pressure; D011759:Pyrrolidines / Q000737:chemistry*; D013816:Thermodynamics; D014753:Vinyl Compounds / Q000737:chemistry*; D014961:X-Ray Diffraction
D005079:Excipients; D011208:Powders; D011759:Pyrrolidines; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); D008825:Miconazole
X‐ray diffractometry; calorimetry (DSC); compression; extrusion; glass transition; mixing; solid dispersions; spectroscopy; spray drying; tableting