In Vitro Consistency Evaluation of Tulobuterol Patch and The Impact of Quality Standard Characteristics on Industrialization
TAN Hua-jin1,2, GUAN Jin3, HE Shu-wang4, FANG Xia-qin1, JIN Wen-zhen1, QIAO Pei-xiang1, ZHANG Yu-jia1, TAN Xiao-chuan1, ZHANG Jian-min3, ZHENG Wen-sheng1*
1. Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing City Key Laboratory of Drug Delivery Technology and Novel Formulation, Beijing 100050, China; 2. Anhui University of Chinese Medicine,Hefei 230012, China; 3. Beijing Shou′er Pharmaceutical Factory, Beijing 101304, China; 4. Shandong DYNE Marine Biopharmaceutical Co., Ltd, Rongcheng 264300, China
Abstract：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.
檀华进, 关晶, 何淑旺, 方夏琴, 靳雯臻, 乔培香, 张宇佳,谭晓川, 张建民, 郑稳生. 妥洛特罗透皮贴剂体外一致性评价及质量标准特性对产业化影响[J]. 中国药学杂志, 2019, 54(21): 1758-1765.
TAN Hua-jin, GUAN Jin, HE Shu-wang, FANG Xia-qin, JIN Wen-zhen, QIAO Pei-xiang, ZHANG Yu-jia, TAN Xiao-chuan, ZHANG Jian-min, ZHENG Wen-sheng. In Vitro Consistency Evaluation of Tulobuterol Patch and The Impact of Quality Standard Characteristics on Industrialization. Chinese Pharmaceutical Journal, 2019, 54(21): 1758-1765.