Early drug development predictions of glass-forming ability and physical stability of drugs
2013 (English)In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 49, no 2, 323-332 p.Article in journal (Refereed) Published
The purpose of this study was to investigate if rapidly measured physical properties can predict glass-forming ability and glass stability of drug compounds. A series of 50 structurally diverse drug molecules were studied with respect to glass-forming ability and, for glass-formers (n = 24), the physical stability upon 1 month of storage was determined. Spray-drying and melt-cooling were used to produce the amorphous material and the solid state was analysed by Differential Scanning Calorimetry (DSC) and Powder X-ray Diffraction. Thermal properties and molecular weight (Mw) were used to develop predictive models of (i) glass-forming ability and (ii) physical stability. In total, the glass-forming ability was correctly predicted for 90% of the drugs from their Mw alone. As a rule of thumb, drugs with Mw greater than 300 g/mole are expected to be transformed to its amorphous state by using standard process technology. Glass transition temperature and Mw predicted the physical stability upon storage correctly for 78% of the glass-forming compounds. A strong sigmoidal relationship (R-2 of 0.96) was identified between crystallization temperature and stability. These findings have the potential to rationalize decisions schemes for utilizing and developing amorphous formulations, through early predictions of glass-forming ability from Mw and physical stability from simple DSC characterization.
Place, publisher, year, edition, pages
2013. Vol. 49, no 2, 323-332 p.
Glass-forming ability, Amorphous stability, Prediction, Molecular weight, Glass transition temperature, Crystallization temperature
IdentifiersURN: urn:nbn:se:uu:diva-204132DOI: 10.1016/j.ejps.2013.03.016ISI: 000319639800027OAI: oai:DiVA.org:uu-204132DiVA: diva2:637734