Please use this identifier to cite or link to this item: https://doi.org/10.3109/03639045.2011.558091
Title: Investigating the effect of moisture protection on solid-state stability and dissolution of fenofibrate and ketoconazole solid dispersions using PXRD, HSDSC and Raman microscopy
Authors: Kanaujia, P.
Lau, G.
Ng, W.K.
Widjaja, E.
Schreyer, M.
Hanefeld, A.
Fischbach, M.
Saal, C.
Maio, M.
Tan, R.B.H. 
Keywords: Degree of crystallinity
Melt extrusion
Moisture protection
Solid dispersion
Stability studies
Issue Date: Sep-2011
Citation: Kanaujia, P., Lau, G., Ng, W.K., Widjaja, E., Schreyer, M., Hanefeld, A., Fischbach, M., Saal, C., Maio, M., Tan, R.B.H. (2011-09). Investigating the effect of moisture protection on solid-state stability and dissolution of fenofibrate and ketoconazole solid dispersions using PXRD, HSDSC and Raman microscopy. Drug Development and Industrial Pharmacy 37 (9) : 1026-1035. ScholarBank@NUS Repository. https://doi.org/10.3109/03639045.2011.558091
Abstract: Enhanced dissolution of poorly soluble active pharmaceutical ingredients (APIs) in amorphous solid dispersions often diminishes during storage due to moisture-induced re-crystallization. This study aims to investigate the influence of moisture protection on solid-state stability and dissolution profiles of melt-extruded fenofibrate (FF) and ketoconazole (KC) solid dispersions. Samples were kept in open, closed and Activ-vials® to control the moisture uptake under accelerated conditions. During 13-week storage, changes in API crystallinity were quantified using powder X-ray diffraction (PXRD) (Rietveld analysis) and high sensitivity differential scanning calorimetry (HSDSC) and compared with any change in dissolution profiles. Trace crystallinity was observed by Raman microscopy, which otherwise was undetected by PXRD and HSDSC. Results showed that while moisture protection was ineffective in preventing the re-crystallization of amorphous FF, KC remained X-ray amorphous despite 5% moisture uptake. Regardless of the degree of crystallinity increase in FF, the enhanced dissolution properties were similarly diminished. Moisture uptake above 10% in KC samples also led to re-crystallization and significant decrease in dissolution rates. In conclusion, eliminating moisture sorption may not be sufficient in ensuring the stability of solid dispersions. Analytical quantification of API crystallinity is crucial in detecting subtle increase in crystallinity that can diminish the enhanced dissolution properties of solid dispersions. © 2011 Informa Healthcare USA, Inc.
Source Title: Drug Development and Industrial Pharmacy
URI: http://scholarbank.nus.edu.sg/handle/10635/89280
ISSN: 03639045
DOI: 10.3109/03639045.2011.558091
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