他达拉非纳米晶体干混悬剂的制备与质量评价

Preparation and quality evaluation of Tadalafil Nanocrystal Dry Suspensions

目的制备他达拉非纳米晶体干混悬剂,并评价其质量。方法采用介质研磨法将他达拉非制备成纳米晶体,通过喷雾干燥工艺固化成固体颗粒,并与其他辅料混合后制备成干混悬剂;以沉降体积比和再分散性作为评价指标,通过单因素实验筛选干混悬剂中填充剂和助悬剂的种类及用量;通过扫描电镜观察他达拉非原料药、固化前后的纳米晶体颗粒以及干混悬剂的微观结构;比较他达拉非纳米晶体干混悬剂与市售他达拉非片剂的体外药物溶出速率。结果经实验优化得到他达拉非纳米晶体干混悬剂的处方组成为:填充剂甘露醇用量为40%,助悬剂黄原胶用量为25%;固化前后他达拉非纳米晶体的粒径分布未发生显著变化;在扫描电镜下可以观察到他达拉非原料药呈片状或柱状分布,纳米晶体呈不规则颗粒状分布,喷雾干燥后呈疏松粉末状;与他达拉非片相比,他达拉非纳米晶体干混悬剂药物溶出速度更快,在10 min内药物可完全溶出。结论将他达拉非制备成纳米晶体干混悬剂,处方设计合理,工艺可行,药物溶出速率显著提高,有望提高生物利用度。

Objective To prepare Tadalafil Nanocrystal Dry Suspensions and evaluate the preparation quality.Methods The tadalafil nanocrystal was prepared by wet media milling method,which was solidified into solid particles through a spray drying process,and mixed with other excipients to prepare dry suspensions.The types and amount of filler and suspending agent in dry suspensions were determined by single factor experiment.Scanning electron microscopy was used to observe the microstructure of tadalafil nanocrystal before and after being solidified and in dry suspensions.The in vitro drug dissolution rates of Tadalafil Nanocrystal Dry Suspensions and commercial Tadalafil Tablets were compared.Results The formulation of Tadalafil Nanocrystal Dry Suspensions was as follows:the amount of mannitol 40%,and the amount of xanthan gum 25%.The particle size distribution of tadalafil nanocrystal did not change significantly before and after being solidified.Under scanning electron microscopy,it was observed that tadalafil was distributed in plate-like,the nanocrystal was distributed in irregular particles,and the spray-dried particles was loose powder.Compared with Tadalafil Tablets,Tadalafil Nanocrystal Dry Suspensions had a faster dissolution rate,and the drug could be completely dissolved within 10 min.Conclusion Tadalafil was prepared as a nanocrystal dry suspensions.The formulation design was reasonable and the process was feasible.The drug dissolution rate was significantly improved,and therefore the drug bioavailability is expected to be improved.