Application of Carrier and Plasticizer to Improve the Dissolution and Bioavailability of Poorly Water-Soluble Baicalein by Hot Melt Extrusion
Application of Carrier and Plasticizer to Improve the Dissolution and Bioavailability of Poorly Water-Soluble Baicalein by Hot Melt Extrusion
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DOI：
10.1208/s12249-013-0071-x
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发表时间：
2014-02
影响因子：
3.3
通讯作者：
Yilan Zhang;Rui Luo;Yi Chen;X. Ke;D. Hu;Miaomiao Han
中科院分区：
文献类型：
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作者：
Yilan Zhang;Rui Luo;Yi Chen;X. Ke;D. Hu;Miaomiao Han
摘要采用热熔挤压法制备黄芩素（一种高熔点难溶药物）的固体分散体，研究了黄芩素的合适配方。通过计算汉森溶解度参数，评价熔炼工艺条件，测定熔体溶解度，选择合适的载体和增塑剂。评价了HME法制备的固体分散体的性能。将挤出物的溶出性能与纯药和物理混合物进行了比较。采用差示扫描量热法（DSC）、粉末x射线衍射（PXRD）和傅里叶变换红外光谱（FTIR）对挤出物的理化性质进行了表征。评估了小猎犬口服给药后的相对生物利用度。因此，选择Kollidon VA64和Eudragit EPO作为两个载体；增塑剂为Cremophor RH。所有挤出物的溶解都有明显改善。DSC和PXRD结果表明，黄芩苷在挤出物中呈无定形。FTIR光谱揭示了药物与聚合物之间的相互作用。口服后，含有VA64和EPO的固体分散体的相对生物利用度是比较的，分别比纯药物高2.4倍和2.9倍。图ᅟ
AbstractThe objective of this study was to develop a suitable formulation for baicalein (a poorly water-soluble drug exhibiting high melting point) to prepare solid dispersions using hot melt extrusion (HME). Proper carriers and plasticizers were selected by calculating the Hansen solubility parameters, evaluating melting processing condition, and measuring the solubility of obtained melts. The characteristic of solid dispersions prepared by HME was evaluated. The dissolution performance of the extrudates was compared to the pure drug and the physical mixtures. Physicochemical properties of the extrudates were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR). Relative bioavailability after oral administration in beagle dogs was assessed. As a result, Kollidon VA64 and Eudragit EPO were selected as two carriers; Cremophor RH was used as the plasticizer. The dissolution of all the extrudates was significantly improved. DSC and PXRD results suggested that baicalein in the extrudates was amorphous. FTIR spectroscopy revealed the interaction between drug and polymers. After oral administration, the relative bioavailability of solid dispersions with VA64 and EPO was comparative, about 2.4- and 2.9-fold greater compared to the pure drug, respectively. Figureᅟ