A Novel Protocol Using Small-Scale Spray-Drying for the Efficient Screening of Solid Dispersions in Early Drug Development and Formulation, as a Straight Pathway from Screening to Manufacturing Stages

Pharmaceuticals
Aymeric OussetKalliopi Dodou

Abstract

This work describes a novel screening strategy that implements small-scale spray-drying in early development of binary amorphous solid dispersions (ASDs). The proposed methodology consists of a three-stage decision protocol in which small batches (20⁻100 mg) of spray-dried solid dispersions (SDSDs) are evaluated in terms of drug⁻polymer miscibility, physical stability and dissolution performance in bio-predictive conditions. The objectives are to select the adequate carrier and drug-loading (DL) for the manufacturing of robust SDSD; and the appropriate stabilizer dissolved in the liquid vehicle of SDSD suspensions, which constitutes the common dosage form used during non-clinical studies. This methodology was verified with CDP146, a poorly water soluble (<2 µg/mL) API combined with four enteric polymers and four stabilizers. CDP146/HPMCAS-LF 40:60 (w/w) and 10% (w/v) PVPVA were identified as the lead SDSD and the best performing stabilizer, respectively. Lead SDSD suspensions (1⁻50 mg/mL) were found to preserve complete amorphous state during 8 h and maintain supersaturation in simulated rat intestinal fluids during the absorption window. Therefore, the implementation of spray-drying as a small-scale screening approach allowed ...Continue Reading

References

Nov 30, 2006·International Journal of Toxicology·Shayne C GadHeide Robbe
Dec 23, 2006·International Journal of Pharmaceutics·Kirk A OverhoffRobert O Williams
Jul 14, 2010·Journal of Pharmaceutical Sciences·Jared A BairdLynne S Taylor
Aug 31, 2010·Journal of Pharmaceutical Sciences·Jessica AlbersPeter Kleinebudde
Jul 24, 2012·International Journal of Pharmaceutics·Amrit PaudelGuy Van den Mooter
Feb 12, 2013·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Nicole WyttenbachSusanne Page
Sep 24, 2013·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Chau Le-Ngoc VoBeom-Jin Lee
Oct 1, 2013·Expert Opinion on Drug Metabolism & Toxicology·Evan A Thackaberry
Jan 21, 2014·International Journal of Pharmaceutics·Keisuke UedaKunikazu Moribe
Feb 18, 2015·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Fan MengHarsh Chauhan
Apr 29, 2015·Journal of Pharmaceutical Sciences·Tapan ParikhAbu T M Serajuddin
Jul 16, 2015·Journal of Pharmaceutical Sciences·Yan He, Chris Ho
Feb 1, 2014·Acta Pharmaceutica Sinica. B·Yanbin Huang, Wei-Guo Dai
Nov 19, 2015·Acta Pharmaceutica Sinica. B·Sandeep Kalepu, Vijaykumar Nekkanti
Dec 27, 2015·Advanced Drug Delivery Reviews·Abhishek Singh, Guy Van den Mooter
Jul 6, 2016·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Shrawan BaghelNiall J O'Reilly
Aug 22, 2017·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Ahmad ZiaeeGavin Walker

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Citations

Nov 16, 2020·International Journal of Pharmaceutics·Wei ZhangTao Chen

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Methods Mentioned

BETA
X-ray
light microscopy
Atomic force microscopy
Raman

Software Mentioned

Axiovision
Universal Analysis
Universal Analysis 2000
Matlab
Empower
Eva DIFFRAC - SUITE
iC Raman
TA

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