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The Influence of Solvent Evaporation Rate on Solid Dispersion Initial Quality and Stability: A Fast Screening Approach
1 , 2 , 1 , 3 , 1 , * 1
1  Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.
2  School of Pharmacy, University of Otago, P.O. Box 56 Dunedin, New Zealand.
3  Quality and Technology, Section Spectroscopy and Chemometrics, Faculty of Life Sciences, University of Copenhagen, Rolighedsvej 30, 1958 Frederiksberg, Denmark.

Abstract: The potential of increased drug release and thus increasing bioavailability of poorly water soluble drugs formulated as solid dispersion is well recognized. When preparing solid dispersions, an important aim is to disperse the drug compound in amorphous form within the polymer, and thus exploit the increased solubility of the amorphous drug. Due to the increased free energy of the amorphous drug, recrystallization during solid dispersion preparation and storage are issues of concern. Up to date, one of the preferred approaches in preparing solid dispersions is the solvent evaporation based methods due to its convenience and possibility for larger scale manufacturing. The methods include rotation evaporation, evaporation using a stream of nitrogen, spin coating and spray drying. However, the evaporation rateis often uncontrolled and in many cases even unknown. In the present study, the effect of evaporation rate on the initial solid state of the solid dispersion was investigated using piroxicam as a low solubility model drug and polyvinylpyrrolidone (PVP) as a model polymer. In addition, the stability of these preparations was examined upon storage up to one month. Using experimental design, the evaporation rate was compared against drug:polymer ratio and polymer molecular weight. The results show that the so far unanticipated effect of evaporation rate accounts for the largest effect followed by drug:polymer ratio on both the initial quality of solid dispersion and the physical stability of the amorphous drug upon storage. This study demonstrated the importance of careful evaluation of the evaporation rate profile when comparing solid dispersion systems prepared by different solvent evaporation methods.
Keywords: solid dispersions, evaporation rate, solvent evaporation, experimental design, screening