| 摘要: | 根據統計，每年台灣丟棄的廢棄藥物至少達193噸以上，而抗生素在其中占了相當大的比例。然而，四環素是世界上第二大類抗生素，也是最常見的獸醫用藥。因此，本研究的目的是從廢棄抗生素膠囊中回收其活性藥物成分(API)鹽酸四環素（TCH）作為案例研究。此研究包括兩個部分：（1）根據國際醫藥法規協和會（ICH）所訂定人類用藥之製程殘留溶劑標準，選擇TCH再結晶之溶劑以及（2）將第一部分的結果延伸至500 ml的攪拌槽規模並混合KINGDOM®和NOVABIOTIC®兩種市售的抗生素膠囊，從其中回收鹽酸四環素。本研究將探討混合、老化時間、老化溫度、反溶劑添加速率以及攪拌速率對製程的影響。在25℃下利用甲醇以300 rpm攪拌1.5 小時固液萃取其中的鹽酸四環素，經0.22 μm聚偏二氟乙烯(PVDF)膜過濾未溶解之物質。再以9.9 毫升/分鐘的速率添加甲基叔丁基醚(MTBE)作為反溶劑，添加後以900 rpm攪拌老化2小時，利用1μm棉絨纖維濾紙過濾蒐集固體。鹽酸四環素的回收率達到73.1％且HPLC純度測定達到99.2％。藥物回收的技術已屈指可數，然而相比之下利用結晶製程回收藥物更是乏人問津。此研究不僅是一個新穎的方法，更具其他優點，例如製程操作簡單且快速也具再現性。最重要的是，其中的活性藥物成分(API)能夠直接被回收而非分解或轉換成其他物質。;According to the statistics, at least 193 tons of drugs are thrown away in Taiwan every year and antibiotics make up a large proportion. Among them, tetracycline is the second largest class of antibiotics in the world, and the most common veterinary drug. For this reason, the aim of this research is to recycle tetracycline hydrochloride (TCH), one of the antibiotics, from capsule wastes as a case study. Experiments include two parts: (1) solvent screening and selection for recrystallization of purchased TCH according to the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guideline Q3C (R6) on impurities: Guideline for residual solvents, and (2) the results based on the first part were extended to recycle TCH from different brands of capsules (KINGDOM® and NOVABIOTIC®) in a 500 ml stirred tank scale. The effects of mixing, aging time, aging temperature, addition rates, and agitation rates on TCH recycling are studied. Solid-liquid extraction was applied to the capsules in methanol with an agitation rate of 300 rpm for 1.5 hours, and filtration by a 0.22 μm PVDF filter membrane. The addition of antisolvent, MTBE with an addition rate of 9.9 ml/min, with an agitation rate of 900 rpm, and aged for 2 hours at 25℃, then filtered through a 1μm alpha cotton cellulose filter paper to collect the solids. The recovery rates of TCH achieved 73.1%, and the HPLC assay achieved 99.2%. A novel, fast and simple operation, and reproducible recycling processes were carried out in this research. Most importantly, the original pure form of the active pharmaceutical ingredient (API) can be recovered directly instead of decomposing or transforming into some other components. |
