Characterization of heterogeneity and spatial distribution of phases in complex solid dispersions by thermal analysis by structural characterization and X-ray micro computed tomography
| Autor: | Samy Yassin, Sheng Qi, Peter S. Belton, J. Axel Zeitler, Mike Reading, Muqdad Alhijjaj |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Materials science
Polymers Drug Compounding Analytical chemistry Pharmaceutical Science 02 engineering and technology 030226 pharmacology & pharmacy Miscibility hot melt extrusion law.invention Polyethylene Glycols Excipients 03 medical and health sciences 0302 clinical medicine solid dispersions law Phase (matter) Vitamin E Pharmacology (medical) thermal analysis by structural characterization (TASC) Crystallization Thermal analysis Dissolution Pharmacology Drug Carriers Felodipine Organic Chemistry XμCT tomography X-Ray Microtomography 021001 nanoscience & nanotechnology Microstructure injection moulding Characterization (materials science) Drug Liberation Pharmaceutical Preparations Solubility Molecular Medicine drug-polymer miscibility phase separation 0210 nano-technology Drug carrier Biotechnology Research Paper |
| Zdroj: | Pharmaceutical Research |
| Popis: | Purpose This study investigated the effect of drug-excipient miscibility on the heterogeneity and spatial distribution of phase separation in pharmaceutical solid dispersions at a micron-scale using two novel and complementary characterization techniques, thermal analysis by structural characterization (TASC) and X-ray micro-computed tomography (XμCT) in conjunction with conventional characterization methods. Method Complex dispersions containing felodipine, TPGS, PEG and PEO were prepared using hot melt extrusion-injection moulding. The phase separation behavior of the samples was characterized using TASC and XμCT in conjunction with conventional thermal, microscopic and spectroscopic techniques. The in vitro drug release study was performed to demonstrate the impact of phase separation on dissolution of the dispersions. Results The conventional characterization results indicated the phase separating nature of the carrier materials in the patches and the presence of crystalline drug in the patches with the highest drug loading (30% w/w). TASC and XμCT where used to provide insight into the spatial configuration of the separate phases. TASC enabled assessment of the increased heterogeneity of the dispersions with increasing the drug loading. XμCT allowed the visualization of the accumulation of phase separated (crystalline) drug clusters at the interface of air pockets in the patches with highest drug loading which led to poor dissolution performance. Semi-quantitative assessment of the phase separated drug clusters in the patches were attempted using XμCT. Conclusion TASC and XμCT can provide unique information regarding the phase separation behavior of solid dispersions which can be closely associated with important product quality indicators such as heterogeneity and microstructure. Electronic supplementary material The online version of this article (doi:10.1007/s11095-016-1923-3) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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