In vitro and in vivo assessment of hydroxypropyl cellulose as functional additive for enabling formulations containing itraconazole
| Autor: | Thilo Faber, Yann Pellequer, Marius Monschke, Alf Lamprecht, Karl G. Wagner, Anna K. Krome, Rafael D. Bachmaier, Edmont Stoyanov |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
HPC
hydroxypropyl cellulose Hot-melt extrusion Biphasic dissolution AcN acetonitrile Pharmaceutical Science DMSO dimethyl sulfoxide PM physical mixture AUC area under the curve chemistry.chemical_compound DSC differential scanning calorimetry Pharmacy and materia medica Differential scanning calorimetry HPMC hydroxypropyl methyl cellulose HPMC In vivo BCS biopharmaceutical classification system TG glass transition temperature NCE new chemical entity Amorphous solid dispersion Dissolution chemistry.chemical_classification Supersaturation Chemistry Hydroxypropyl cellulose HME hot-melt extrusion Polymer ASD amorphous solid dispersion GI gastrointestinal ITZ itraconazole Bioavailability KTZ ketoconazole RS1-441 Chemical engineering OH-ITZ hydroxy-itraconazole SD spray-drying XRPD x-ray powder diffraction HPC API active pharmaceutical ingredient FaSSIF fasted state simulated intestinal fluid Ternary operation Research Paper |
| Zdroj: | International Journal of Pharmaceutics: X, Vol 3, Iss, Pp 100076-(2021) International Journal of Pharmaceutics: X |
| ISSN: | 2590-1567 |
| DOI: | 10.1016/j.ijpx.2021.100076 |
| Popis: | Using polymers as additives to formulate ternary amorphous solid dispersions (ASDs) has successfully been established to increase the bioavailability of poorly soluble drugs, when one polymer is not able to provide both, stabilizing the drug in the matrix and the supersaturated solution. Therefore, we investigated the influence of low-viscosity hydroxypropyl cellulose (HPC) polymers as an additive in HPMC based ternary ASD formulations made by hot-melt extrusion (HME) on the bioavailability of itraconazole (ITZ). The partitioning potential of the different HPC grades was screened in biphasic supersaturation assays. Solid-state analytics were performed using differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD). The addition of HPCs, especially HPC-UL, resulted in a superior partitioned amount of ITZ in biphasic supersaturation assays. Moreover, the approach in using HPCs as an additive in HPMC based ASDs led to an increase in partitioned ITZ compared to Sporanox® in biorelevant biphasic dissolution studies. The results from the biphasic dissolution experiments correlated well with the in vivo studies, which revealed the highest oral bioavailability for the ternary ASD comprising HPC-UL and HPMC. Graphical abstract Unlabelled Image Highlights • Increased partitioning rate of itraconazole using low-viscosity HPC polymers. • Enhanced bioavailability of itraconazole using HPC-UL as functional additive. • Ternary amorphous solid dispersion with higher performance than Sporanox®. |
| Databáze: | OpenAIRE |
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