Physical stability of drugs after storage above and below the glass transition temperature: Relationship to glass-forming ability

International Journal of Pharmaceutics
Amjad AlhalawehChristel A S Bergström

Abstract

Amorphous materials are inherently unstable and tend to crystallize upon storage. In this study, we investigated the extent to which the physical stability and inherent crystallization tendency of drugs are related to their glass-forming ability (GFA), the glass transition temperature (Tg) and thermodynamic factors. Differential scanning calorimetry was used to produce the amorphous state of 52 drugs [18 compounds crystallized upon heating (Class II) and 34 remained in the amorphous state (Class III)] and to perform in situ storage for the amorphous material for 12h at temperatures 20°C above or below the Tg. A computational model based on the support vector machine (SVM) algorithm was developed to predict the structure-property relationships. All drugs maintained their Class when stored at 20°C below the Tg. Fourteen of the Class II compounds crystallized when stored above the Tg whereas all except one of the Class III compounds remained amorphous. These results were only related to the glass-forming ability and no relationship to e.g. thermodynamic factors was found. The experimental data were used for computational modeling and a classification model was developed that correctly predicted the physical stability above the Tg....Continue Reading

References

Jun 28, 2002·International Journal of Pharmaceutics·Bruno C HancockMatthew P Mullarney
Aug 24, 2006·Pharmaceutical Research·Patrick J MarsacLynne S Taylor
Aug 26, 2006·Pharmaceutical Research·Patrick J MarsacLynne S Taylor
Aug 28, 2007·Journal of Pharmaceutical Sciences·Chandan Bhugra, Michael J Pikal
Apr 28, 2009·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Kirsten A GraeserThomas Rades
Jul 14, 2010·Journal of Pharmaceutical Sciences·Jared A BairdLynne S Taylor
Apr 6, 2013·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Denny Mahlin, Christel A S Bergström
Mar 7, 2014·Physical Chemistry Chemical Physics : PCCP·M AlonsoF De Proft
Jul 12, 2014·Molecular Pharmaceutics·Amjad AlhalawehChristel A S Bergström
Jul 31, 2014·The Journal of Physical Chemistry. B·Niraj S TrasiLynne S Taylor
Nov 2, 2014·Journal of Chemical Information and Modeling·Ahmad AlzghoulChristel A S Bergström

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Citations

May 31, 2016·Journal of Pharmaceutical Sciences·Katarzyna NurzyńskaFrank Gommer
Oct 25, 2016·Journal of Pharmaceutical Sciences·M Teresa ViciosaHermínio P Diogo
May 20, 2017·Pharmaceutical Research·Khadijah EduengChristel A S Bergström
Aug 3, 2018·The Journal of Pharmacy and Pharmacology·Felix DitzingerMartin Kuentz
Dec 6, 2019·Biological & Pharmaceutical Bulletin·Yuya HirakawaMasahiro Goto
Jul 4, 2019·Pharmaceutics·Bożena KarolewiczIgor Mucha
Nov 14, 2018·Journal of Pharmaceutical Sciences·Amjad AlhalawehChristel A S Bergström
Aug 21, 2020·Journal of Pharmaceutical Sciences·Andrew Toye Ojo, Ping I Lee
Feb 21, 2021·Journal of Pharmaceutical Sciences·Martin KuentzBrendan T Griffin
Mar 7, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Fan XieGuy Van den Mooter
Mar 18, 2019·Journal of Pharmaceutical Sciences·Lasse Ingerslev BlaabjergHolger Grohganz
Apr 30, 2021·International Journal of Pharmaceutics·Dani Lakshman YarlagaddaKrishnamurthy Bhat
Aug 11, 2021·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·Hecong QinJohn Kurhanewicz
Jun 5, 2020·Molecular Pharmaceutics·Nicole WyttenbachMartin Kuentz

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Methods Mentioned

BETA
differential scanning calorimetry

Software Mentioned

ADMET Predictor

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