茶碱两次脉冲释药微丸的研制及体外释放的影响因素

Studies on preparation of theophylline twice pulsed release pellets and various influence factors

目的制备茶碱两次不等剂量脉冲释药微丸并考察体外释放影响因素。方法采用挤出滚圆法制备载药速释丸芯,用流化床包衣技术,以水溶胀性材料交联羧甲基纤维素钠(CCNa)为内包衣溶胀层,乙基纤维素水分散体(Surelease E-7-19010)为外包衣控释层制备第二次脉冲释药微丸,并考察溶胀层种类、溶胀层和控释层包衣后增加的质量、介质pH值以及微丸粒径等对药物释放的影响。对所制得的第二次脉冲释药微丸再进行包衣,即在其外层继续包上茶碱层和普通薄膜衣制备两次脉冲释药微丸,并考察了微丸中第一剂量茶碱的体外溶出度、含量均匀度及两次脉冲释药微丸体外溶出度。结果溶胀层和控释层包衣后增加的质量以及微丸粒径等对第二剂量脉冲释药微丸的释药时滞和释药速率均具有显著影响,但不受溶出介质pH值的影响。结论两次脉冲释药微丸中的第一脉冲释药在45 min内能够达到理想的溶出度,其含量均匀度符合要求,时滞时间达到8.5 h开始第二剂量脉冲释药,时滞后3 h释药达到80%。进一步的实验表明茶碱层和普通薄膜衣对茶碱第二次脉冲释药速率几乎没有影响,只是时滞延长了0.5h。

Obtective To prepare the theophylline twice pulsed release pellets(PRP).Methods Theophylline–loaded pellets were prepared by extrusion-spheronization technology.The second PCRP were prepared with croscarmellose sodium(CCNa) as the inner swelling layer and ethylcellulose aqueous dispersion(Surelease) as the outer controlled layer.The influences of the coating material of the swelling layer,the coating level of the swelling layer,the controlled layer,the pH values of the media and the size of final pellets on the release of theophylline from the second PRP were investigated respectively.The second PRP were further coated to prepare the first PRP with normal coating material which contained theophylline.Dissolution and content uniformity of the first PRP and twice PRP were also investigated.Result The coating lever of the swelling layer,the controlled layer and the size of final pellets had significant effect on the lag time and the release rate of theophylline from the second PRP.Conclusion Theophylline of the first dose could dissolute completely within 45 min in vitro and content uniformity of it was ideal.After the lag time of 8.5 h,the drug of the second dose release from twice PRP was more than80% within the following 3 h.Further test indicated that outer coating had no influence on the release behaviour of the drug of the second dose.