High drug load, stable, manufacturable and bioavailable fenofibrate formulations in mesoporous silica: a comparison of spray drying versus solvent impregnation methods
| Autor: | Kennan C. Marsh, Rajeev Gokhale, Reginald B. H. Tan, Wai Kiong Ng, David Cheng Thiam Tan, Steven A. Nowak, Anastasia Windy Irwan, Xueming Liu, Shiqi Hong, Leonard Chia, Shoucang Shen |
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| Rok vydání: | 2014 |
| Předmět: |
Materials science
Chemistry Pharmaceutical Drug Compounding Biological Availability Pharmaceutical Science 02 engineering and technology 030226 pharmacology & pharmacy 03 medical and health sciences Crystallinity Dogs 0302 clinical medicine Differential scanning calorimetry Fenofibrate MCM-41 Animals Desiccation Dissolution Hypolipidemic Agents Chromatography General Medicine Factorial experiment Mesoporous silica Silicon Dioxide 021001 nanoscience & nanotechnology Bioavailability Chemical engineering Spray drying Solvents 0210 nano-technology Porosity |
| Zdroj: | Drug Delivery. 23:316-327 |
| ISSN: | 1521-0464 1071-7544 |
| DOI: | 10.3109/10717544.2014.913323 |
| Popis: | 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 2(3) 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. |
| Databáze: | OpenAIRE |
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