High drug load, stable, manufacturable and bioavailable fenofibrate formulations in mesoporous silica: a comparison of spray drying versus solvent impregnation methods

Abstract

Encapsulation of drugs in mesoporous silica using co-spray drying process has been recently explored as potential industrial method. However, the impact of spray drying on manufacturability, physiochemical stability and bioavailability in relation to conventional drug load processes are yet to be fully investigated. Using a 2³ factorial design, this study aims to investigate the effect of drug-loading process (co-spray drying and solvent impregnation), mesoporous silica pore size (SBA-15, 6.5 nm and MCM-41, 2.5 nm) and percentage drug load (30% w/w and 50% w/w) on material properties, crystallinity, physicochemical stability, release profiles and bioavailability of fenofibrate (FEN) loaded into mesoporous silica. From the scanning electronic microscopy (SEM) images, powder X-ray diffraction and Differential scanning calorimetry measurements, it is indicated that the co-spray drying process was able to load up to 50% (w/w) FEN in amorphous form onto the mesoporous silica as compared to the 30% (w/w) for solvent impregnation. The in vitro dissolution rate of the co-spray dried formulations was also significantly (p = 0.044) better than solvent impregnated formulations at the same drug loading. Six-month accelerated stability test at 40 °C/75% RH in open dish indicated excellent physical and chemical stability of formulations prepared by both methods. The amorphous state of FEN and the enhanced dissolution profiles were well preserved, and very low levels of degradation were detected after storage. The dog data for the three selected co-spray-dried formulations revealed multiple fold increment in FEN bioavailability compared to the reference crystalline FEN. These results validate the viability of co-spray-dried mesoporous silica formulations with high amorphous drug load as potential drug delivery systems for poorly water soluble drugs.

• Amorphous
• bioavailability
• dissolution
• MCM-41
• SBA-15
• stability

Acknowledgements

The authors are also thankful for the technical assistance from Ms. Low Yan Ling Shawn.

Declaration of interest

The authors and scientists from AbbVie (formerly Abbott) Private Limited, Singapore, AbbVie Inc. and Institute of Chemical and Engineering Sciences (ICES) designed the study and analyzed and interpreted the data. The authors gratefully acknowledge the financial support provided by AbbVie Private Limited, Singapore, and Economic Development Board, Singapore. All authors contributed to the development of the content. The authors and AbbVie reviewed and approved the publication; the authors maintained control over the final content. S. H., D. C. T. T., X. L., A. W. I., S. A. N., K. M. and R. G. are employees of AbbVie and may own AbbVie stock. S. S., W. K. N., L. S. O. C. and R. T. are employees of Institute of Chemical and Engineering Sciences and have no additional conflicts of interest to report.