目的 制备妥洛特罗透皮贴剂,进行体外一致性评价及探究质量标准特性对产业化的影响。方法 以聚异丁烯B50、聚丁烯、石油树脂为辅料制备妥洛特罗透皮贴剂;采用高效液相色谱法检测样品中药物含量;以显微镜、差热分析仪、傅立叶变换红外光谱仪、持黏力测试仪、溶出试验仪与透皮试验仪等,评价体外一致性;通过考察贴剂溶出情况及其与透皮相关性、贴剂内药物结晶与体外释药机制,探究质量标准特性对产业化的影响。结果 自制贴剂与参比制剂的药物含量、药物结晶、DSC、MATR、耐热耐冷、黏性及赋形型一致性符合要求;在水或pH 7.4、6.8、4.0的磷酸盐缓冲液的溶出介质中,f₂分别为72.516、94.840、90.905和81.760;体外透皮平均渗透率之比为1.02,皮肤滞留量之比为0.88;药物溶解度存在pH依懒性,但体外溶出对pH不敏感,且体外透皮与溶出相关性良好;体外释药受辅料组成与药物结晶等影响。结论 自制贴剂与参比制剂体外评价一致性良好;体外溶出试验可有效反映药物体外透皮渗透吸收过程;并引入制剂内药物结晶评价指标,以提高产业化过程质控检测效率与质量保证;可为本品一致性评价研究、产业化及质量标准改进提供研究参考。

OBJECTIVE To prepare of a torotrope transdermal patch for in vitro consistency evaluation and explor of the impact of quality standard characteristics on industrialization. METHODS The tulobuterol transdermal patch was prepared with polyisobutylene B50, polybutene and petroleum resin as auxiliary excipients. The drug content in the sample was determined by high-performance liquid chromatography; in vitro consistency was evaluated by microscopy, differential thermal analysis, Fourier transform infrared spectroscopy, viscosity tester, dissolution Tester, and transdermal tester. The dissolution of the patch and its relationship with transdermal permeation, drug crystallization and in vitro release mechanism of the patch were studied in order to explore the influence of quality standard characteristics on industrialization. RESULTS The self-made patch and the reference preparation have conformity in the drug content, drug crystallization, DSC, MATR, heat resistance, cold resistance, viscosity and shape. The dissolution tests were performed in medium of water and phosphate buffer (pH 7.4, 6.8, 4.0), and the corresponding f₂ were 72.516, 94.840, 90.905, and 81.760. The average transdermal permeability ratio is 1.02 and the skin retention ratio is 0.88. The drug solubility is pH dependent while the in vitro dissolution is not sensitive to pH. The correlation between transdermal and dissolution in vitro is good. The in vitro release is affected by the composition of the excipients and the crystallization of the drug. CONCLUSION The self-adhesive and the reference preparation have good consistency in vitro evaluation; the in vitro dissolution test can effectively reflect the transdermal permeation and absorption process of the drug in vitro. The drug crystallization evaluation index in the preparation is introduced to improve the quality control detection efficiency and quality assurance in the industrialization process. Research reference is provided for the consistency evaluation research, industrialization and quality standard improvement of this product.