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Open AccessArticle

Stabilisation and Growth of Metastable Form II of Fluconazole in Amorphous Solid Dispersions

1
Department of Drug Forms Technology, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland
2
Centre for Advanced Manufacturing Technologies (CAMT/FPC), Wroclaw University of Science and Technology, Lukasiewicza 5, 50-371 Wroclaw, Poland
*
Author to whom correspondence should be addressed.
Pharmaceutics 2020, 12(1), 12; https://doi.org/10.3390/pharmaceutics12010012
Received: 18 November 2019 / Revised: 11 December 2019 / Accepted: 18 December 2019 / Published: 20 December 2019
(This article belongs to the Special Issue Drug Polymorphism and Dosage Form Design)
The crystallisation of metastable drug polymorphs in polymer matrices has been reported as a successful approach to enhance the solubility of poorly water-soluble drug molecules. This can be achieved using different polymers, drug to polymer ratios and formulation techniques enabling the formation of stable nuclei and subsequent growth of new or metastable drug polymorphs. In this work we elucidated the polymorphism behaviour of a model compound fluconazole (FLU) embedded in solid dispersions with amorphous Soluplus® (SOL) obtained using spray drying and fusion methods. The effect of humidity on the stability of FLU in the obtained dispersions was also evaluated. FLU at a drug content below 40 wt. % stayed amorphous in the dispersions prepared using the fusion method and crystallised exclusively into metastable form II at a drug content above 40 wt. % and 70% relative humidity (RH) conditions. In contrast, a mixture of forms I, II and hydrate of FLU was detected in the spray dried formulations after 14 days of storage at 40 °C/40% RH, with preferential growth of thermodynamically stable form I of FLU. This study highlights the importance of preparation techniques and the drug:polymer ratio in the formulation of amorphous solid dispersions and provides further understanding of the complex crystallisation behaviour of amorphous pharmaceuticals encapsulated in the polymer matrixes. View Full-Text
Keywords: polymorphism; fluconazole; Soluplus; ASD; stability; spray drying; amorphous solid dispersion polymorphism; fluconazole; Soluplus; ASD; stability; spray drying; amorphous solid dispersion
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MDPI and ACS Style

Nowak, M.; Gajda, M.; Baranowski, P.; Szymczyk, P.; Karolewicz, B.; Nartowski, K.P. Stabilisation and Growth of Metastable Form II of Fluconazole in Amorphous Solid Dispersions. Pharmaceutics 2020, 12, 12.

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