尼可地爾(Nicorandil)為治療心絞痛的藥物，本研究主要以其為研究模式藥物，探討於製程放大中對藥品安定性之影響。本研究主要分為五個部份來進行，首先，藉由市售品之安定性試驗觀察含水率對於Nicorandil錠劑的安定性變化，以最佳安定性之市售品所含原料內容進行處方設計；第二部份，藉由前處方試驗，調整原料內容及使用比例，設計出一個較安定且較容易應用於製造過程的藥品處方；第三部份，評估處方藥品性質經製程放大後的影響及確認半成品於製程間的保存條件及暫存週期，得知足量的乾燥劑可維持半成品於暫存期尖的安定性；且錠劑於製程放大後之物理性質及藥物釋放機制並未有明顯改變，藉以證實錠劑於製程放大之穩定性；第四部份，藉由不同的包裝設計，探討Nicorandil錠劑在不同保護機制下的安定性變化，得知防潮性佳的外包裝搭配足量的乾燥劑保存較可維持藥品於架儲期間之安定性；第五部份，藉由溶離試驗，評估錠劑安定性對溶離速率的影響，發現錠劑硬度增加時，會使得其崩解速度變慢，進而減緩其溶離速率變慢。藉由上述研究結果，除了可瞭解Nicorandil錠劑的特性變化，亦可依此做為未來製劑研發上藥物安全性的風險考量依據。 Nicorandil is an anti-anginal drug, also represented as a model drug for the product stability evaluation during scale-up process in this study. This study is divided into five parts. In the first part, observed the stability of nicorandil market product which have different amount of moisture content, and referred the raw material been used from the best stability product for the further formulation development. In the second part, to develop the formulation and the manufacturing process that can be executed stably and easily by pre-formulation study. In the third part, to evaluate the effect of drug product properties after scale-up process, also the storage period and condition of semi-final product during the holding time. The result showed that the sufficient amount of desiccant is necessary for the storage stability maintenance during the holding time, also the physical characteristics and drug release property of nicorandil tablet has no significantly change after scale-up process. In the fourth part, to investigate the stability variance of nicorandil tablet under different package protection. The well moisture resistance package material and desiccant moisture absorption capacity offered the ability to defer the drug degradation and the increase of total impurities. In the last part, to evaluate the effect of the dissolution rate of nicorandil tablet in 0.1N hydrochloride acid dissolution test. The harder tablet obtained from stability test, the slower dissolution rate of nicorandil tablet. With these result, not only the nicorandil tablet characteristics have been investigated, but also as the basis of risk assessment for the drug stability of formulation development in the future.
