黄芩苷乙基纤维素微球鼻腔给药系统的制备研究

Studies on baicalin ethylcellulose microspheres for intranasal administration

该研究采用乳剂-溶剂挥发法制备了黄芩苷乙基纤维素鼻用微球。所得微球圆整度好,载药量及包封率分别为(33.31±0.045)%,(63.34±0.11)%,微球平均粒径37.08μm。XRD结果表明黄芩苷在微球中以结晶状态存在但结晶度较原料药有所降低。DSC结果证实药物被包裹于载体内部,而不同于简单的物理混合物。粉末流动性测试显示微球特别流动能为3.57 m J·g-1;在正应力为15 k Pa时,空气以2 mm·s-1的速度通过微球粉末时气压降值为0.222 k Pa。体外释放试验研究结果显示黄芩苷原料药7 h累积释放接近90%,而黄芩苷微球只达75%,表明微球具有一定的缓释作用。对前7 h释放曲线进行模型拟合,结果显示黄芩苷原料药释放符合一级模型(R2=0.990 4),微球释放符合Riger-Peppas模型(R2=0.961 2)。离体兔鼻黏膜渗透实验显示微球在7 h时单位面积累计释放量是黄芩苷原料药的1.56倍,为下一步体内药动学研究提供了依据。

In this study, solvent evaporation method was used to preparing baicalin ethylcellulose microspheres for intranasal administration. The prepared microspheres were round with certain rough surface. The average drug loading and entrapment efficiency was （33.31 ± 0. 045） %, （63.34 ± 0. 11 ） %, respectively. As the characteristic crystalline peaks of baicalin were observed in the microspheres sample, the result of X-ray diffractometric analysis indicated that the baicalin was present in crystalline form after its entrapment in ethylcellulose matrix. By investigating the thermogram of microspheres sample, it was found that endothermic peak of baicalin was shifted from 211.8 ℃ to 244. 2℃ and associated with the first broad endothermic peak of ethylcellulose. This could confirm that baicalin was loaded into ethylcellulose, nor simply physical mixture. The powder flowability test exhibited that the specific energy of microspheres was 3. 57 mJ · g^-1 and the pressure drop was 2. 22 mBar when air kept the speed of 2 mm·s ^-1 through the powder bed with the force was 15 kPa. The consequence of the baicalin in vitro released from microspheres showed that the pure baicalin sample displayed faster （90%） release than microspheres sample （75%） in 7 h. Fitting model for release curve before 7 h, the results showed that the pure baicalin sample and the microsphere sample accorded with first order model （R2 = 0. 990 4） and Riger-Peppas model（R^2 =0. 961 2）, respectively. Ex vivo rabbit nasal mucosa permeability experiment revealed that the value of cumulative release rate per unit area of the microsphere sample was 1.56 times that of the pure baicalin sample. This provided the foundation for the in vivo pharmacokinetic study.