Biopharmaceutical studies of Tenoxicam

• Main Authors: Yu,Du-Wun, 俞篤文
• Other Authors: Chen,Rei-long
• Format: Others
• Language: zh-TW
• Published: 1996
• Online Access: http://ndltd.ncl.edu.tw/handle/78434416092259969704

碩士 === 國立臺灣大學 === 藥學研究所 === 84 === Tenoxicam為一種非固醇類抗發炎藥(nonsteroidal antiinflammtory drug ), 其藥理機轉為抑制前列腺素的分泌, 發生消炎的作用, 由於本藥 物對滑液組織(synovail tissue)有很好的滲透作用, 故臨床多使用於風 濕性關節炎、關節黏連性脊椎炎、關節外疾病及痛風。 Tenoxicam在胃腸 道黏膜的吸收良好, 因此錠劑的處方設計、不同的結晶型以及顆粒大小, 其物理化學性質不同,是影響崩散和溶離速率進而對吸收的快慢造成影響 。本論文主要分為兩部份,一. 結晶試驗, 二. 體內藥品相等性試驗; 在 結晶試驗中係將 Tenoxicam 原料以各種不同的溶劑 (如, 丙酮、氯仿、 乙醇、氰甲烷) 重新養成結晶, 所得到結晶做紅外線儀、示差熱掃描分析 儀以及 X-Ray 光譜儀等等儀器的定性鑑定, 之後依不同的晶型結構和顆 粒大小,以 , 以溶離機測定其溶離速率。 第二部份體內藥品相等性試驗 是以健康的男性為受試對象, 探討不同處方設計對tenoxicam錠, 在相同 劑量下投與人體 , 按時間抽取血液, 以高效能液相層析儀分析其血中濃 度,比較其在藥物動態學上的性質及是否具有生體相等性。 Tenoxicam is a nonsteroidal anti-inflammatory drug(NSAID) associ- ated with the oxicam group. Its pharmacological mechanism in- cludes weak cyclooxygenase inhibition that reduces the protaglan- din release. Since tenoxicam is easily diffused to synovium and joint cartilage, it is used for rheumatic disease and gout in the clinical treatment. Tenoxicam is completely absorbed by the oral route and is about 99% protein bound in human plasma. So, They are important factors that the different formulations, crystals and particle sizes have different erosion and dissolution to influence absorption rate and extent. The present study were divided into two categories: one was aimed at the polymorphism and another was for a in vivo bioequivalence study. In the partⅠstudy, serveral solvents (ex. acetone, chloroform, ethanol, acetonitrile, etc.) were used tenoxicam crystalization. These crystals were photographed and the charateristics were identify by IR, DSC and X-Ray. For the in vivo study, two tenoxicam 20 mg tablet formulations were tested in 12 healthy male subjects by a balanced crossover design. After oral administration, blood samples were collected at different times and tenoxicam concentrations were analyzed by a validated HPLC method. The pharmacokentic parameters for the two formulations were com- pared according to the following statistical methods: a. ANOVA with residual effect (P< 0.05 for significant differene) b. Statistical powers c. 90% confidence intervals