期刊
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
卷 127, 期 -, 页码 60-70出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejps.2018.10.020
关键词
Ritonavir; Hot-melt extrusion; Solid dispersion; Plasticizer; Solubility enhancement; Dissolution rate
资金
- National Science and Technology Major Project [2017ZX09201-003]
- National Nature Science Foundation of China [21473085]
- Natural Science Foundation of Shandong Province of China [ZR2017BH065, ZR2016CL14]
- College Science and Technology Project of Shandong Province of China [J17KA234]
- Open Project of Shandong Collaborative Innovation Center for Antibody Drugs [CIC-AD1831]
- Doctoral Starting up Foundation of Liaocheng University [318051633]
- Tai-Shan Scholar Research Fund of Shandong Province of China
In this study, novel ritonavir solid dispersion (RTV SD) formulations were prepared with copovidone (PVPVA 64) and optimized plasticizers via hot-melt extrusion (HME) at different extrusion temperature to evaluate the effect of plasticizers on the process of HME. The optimized drug-loading content of RTV SD formulations was around 15% and RTV was converted to the amorphous state and integrated through physical interactions (possibly hydrogen bonding) with the polymeric carrier. Using Span 20 or HSPC as plasticizer, the HME extrusion temperature of RTV SD formulations suggested a decrease of 10 degrees C or 20 degrees C. Furthermore, the in vitro release and the in vivo pharmacokinetics analyses both showed that RTV SD formulations using Span 20 or HSPC as plasticizer possessed better release profiles and bioavailability over RTV bulk powder but showed equal physicochemical characteristics compared to RTV SD formulations without plasticizer. According to the increased drug solubility, enhanced dissolution profiles, superior bioavailability, but decreased extrusion temperature in HME process, the RTV SD formulation using HSPC as plasticizer could be potentially applied in the clinic as an efficient drug delivery system, and HSPC is recommended as an efficient plasticizer for manufacturing RTV SD formulations via HME.
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