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Pharmaceutics 2018, 10(1), 29; https://doi.org/10.3390/pharmaceutics10010029

Prediction of Phase Behavior of Spray-Dried Amorphous Solid Dispersions: Assessment of Thermodynamic Models, Standard Screening Methods and a Novel Atomization Screening Device with Regard to Prediction Accuracy

1
School of Pharmacy and Pharmaceutical Sciences, Faculty of Health Sciences and Wellbeing, University of Sunderland, Sunderland SR13SD, UK
2
UCB Pharma S.A., Drug Delivery Design and Development, B-1420 Braine l’Alleud, Belgium
*
Author to whom correspondence should be addressed.
Received: 11 February 2018 / Revised: 27 February 2018 / Accepted: 2 March 2018 / Published: 7 March 2018
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Abstract

The evaluation of drug–polymer miscibility in the early phase of drug development is essential to ensure successful amorphous solid dispersion (ASD) manufacturing. This work investigates the comparison of thermodynamic models, conventional experimental screening methods (solvent casting, quench cooling), and a novel atomization screening device based on their ability to predict drug–polymer miscibility, solid state properties (Tg value and width), and adequate polymer selection during the development of spray-dried amorphous solid dispersions (SDASDs). Binary ASDs of four drugs and seven polymers were produced at 20:80, 40:60, 60:40, and 80:20 (w/w). Samples were systematically analyzed using modulated differential scanning calorimetry (mDSC) and X-ray powder diffraction (XRPD). Principal component analysis (PCA) was used to qualitatively assess the predictability of screening methods with regards to SDASD development. Poor correlation was found between theoretical models and experimentally-obtained results. Additionally, the limited ability of usual screening methods to predict the miscibility of SDASDs did not guarantee the appropriate selection of lead excipient for the manufacturing of robust SDASDs. Contrary to standard approaches, our novel screening device allowed the selection of optimal polymer and drug loading and established insight into the final properties and performance of SDASDs at an early stage, therefore enabling the optimization of the scaled-up late-stage development. View Full-Text
Keywords: amorphous solid dispersions; miscibility; solid state properties; spray dryer; screening; polymers; Flory–Huggins theory; phase diagram amorphous solid dispersions; miscibility; solid state properties; spray dryer; screening; polymers; Flory–Huggins theory; phase diagram
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Ousset, A.; Chavez, P.-F.; Meeus, J.; Robin, F.; Schubert, M.A.; Somville, P.; Dodou, K. Prediction of Phase Behavior of Spray-Dried Amorphous Solid Dispersions: Assessment of Thermodynamic Models, Standard Screening Methods and a Novel Atomization Screening Device with Regard to Prediction Accuracy. Pharmaceutics 2018, 10, 29.

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