滴通鼻炎喷涂凝胶剂体外释放度及大鼠鼻黏膜毒性研究

Study on in Vitro Release and Nasal Mucosal Toxicity of Ditong Biyan Spray Gel

关键词:  滴通鼻炎喷涂凝胶剂  体外释放度  鼻黏膜毒性  缓释制剂

Key words:  Ditong Biyan Spray Gel  in vitro release test  nasal mucosal toxicity  sustained release preparation

摘要:

目的 研究滴通鼻炎喷涂凝胶剂的体外药物释放规律及鼻黏膜毒性。方法 采用无膜溶出法进行体外释放度试验，测定药物的累积溶蚀率和释放率，对黄芩苷、盐酸麻黄碱释药行为拟合数学模型进行分析；通过打喷嚏试验考察本品对大鼠的宏观刺激性，并结合HE染色法观察本品鼻黏膜毒性。结果 溶出曲线表明累积溶蚀率与累积释放率有较强线性关系，黄芩苷、盐酸麻黄碱体外释放符合一级动力学方程具缓释特征。本品对大鼠鼻腔有一定刺激性但停药可恢复；气管、支气管和肺部，均未出现红肿、充血等现象；HE染色表明，本品对大鼠鼻黏膜有轻微损伤，停药7 d后，除阳性组黏膜固有层可见腺管上皮细胞发生轻度空泡变性，黏膜上皮细胞发生变性、坏死，固有层充血、出血外，其余各组均可恢复正常。结论 本品为溶蚀与扩散相结合的缓释制剂，对鼻黏膜毒性较小，停药可恢复，安全性较高。

Abstract:

OBJECTIVE To study the release characteristics in vitro and nasal mucosal toxicity of Ditong Biyan Spray Gel. METHODS The cumulative dissolution rate and release rate of Ditong Biyan Spray Gel were determined by non-membrane dissolution method in vitro release test. And then the release behavior of baicalin and ephedrine hydrochloride were fitted with mathematical model. The macro-irritation and the nasal mucosal toxicity of Ditong Biyan Spray Gel were conducted by sneezing experiment and HE staining method. RESULTS There was a strong linear relationship between the cumulative dissolution rate and the cumulative release rate in the dissolution curve. Furthermore, the release of baicalin and ephedrine hydrochloride in vitro conforms to the first-order kinetic equation with sustained release characteristics. This preparation was irritating to the nasal cavity of rats, but it could recover after discontinuation of drug. No redness, congestion and other phenomena in trachea, bronchus and lungs. HE staining showed that this preparation had slight damage to the nasal mucosa of rats. After 7 days of withdrawal, there were slight vacuolar degeneration and necrosis of glandular epithelial cells in the propria mucosa of positive group, and the other groups could recover to normal. CONCLUSION Ditong Biyan Spray Gel is a sustained-release preparation combined with dissolution and diffusion. It is a safe preparation with low toxicity to nasal mucosa, and it can recovery after discontinuation.