坎地沙坦西莱西酯固体分散体的配方优化

IF 0.2 Q4 PHARMACOLOGY & PHARMACY Asian Journal of Pharmaceutical Research and Health Care Pub Date : 2023-01-01 DOI:10.4103/ajprhc.ajprhc_104_22
S. Kothawade, V. Pande
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引用次数: 1

摘要

背景:坎地沙坦西列地酯(CC)是坎地沙坦的一种非活性前药,在胃肠道吸收过程中迅速水解成活性坎地沙坦,从而达到降压作用。由于其水溶性弱,CC肠吸收不足,口服生物利用度低。目的:本研究的目的是使药物CC更易溶于水。材料与方法:以低粘度羟丙基甲基纤维素(HPMC) E5LV为原料,通过喷雾干燥法制备固体分散体。结果:溶出度、傅里叶变换红外光谱、扫描电镜(SEM)、差示扫描量热仪(DSC)和x射线衍射对制备的固体分散体进行了表征。从扫描电镜,DSC和x射线粉末衍射实验的结果可以看出,CC从结晶状态非晶化。对比纯CC和固体分散体,前者溶出率更高。HPMC E5LV的表面活性剂和润湿性能减缓了脱硝过程,并具有抗塑化作用,提高了固体分散体的溶解度和稳定性。结论:本品为弱水溶性药物,在固体分散体中具有较好的溶解性。
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Formulation optimization of solid dispersion of candesartan cilexetil
Context: Antihypertensive effects were achieved by quickly hydrolyzing candesartan cilexetil (CC), an inactive prodrug of candesartan, into active candesartan during absorption in the gastrointestinal tract. Due to its weak water solubility, CC has an inadequate intestinal absorption and a low oral bioavailability. Aim: The goal of this study was to make the medication CC more soluble in water. Materials and Methods: Low viscosity hydroxypropyl methylcellulose (HPMC) E5LV was used to prepare the solid dispersions through spray drying. Results: Study of dissolution, Fourier transform infrared spectroscopy, scanning electron microscopy (SEM), differential scanning calorimeter (DSC), and X-ray diffraction characterized the prepared solid dispersions. CC amorphized from its crystallized state, as shown by the findings from the SEM, DSC, and X-ray powder diffraction experiments. Comparing pure CC and solid dispersion, the dissolution rate was higher with the former. The surfactant and wetting property of HPMC E5LV slowed devitrification and had an anti-plasticization impact, increasing the solubility and stability of the solid dispersion. Conclusion: The final results indicated that the CC, a weakly water-soluble medication, dissolved much better in the solid dispersions.
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