以擠壓搓圓法製備傳統中藥（六味地黃丸）圓粒新劑型之統計適宜化   全文下載

Statistical Optimization of Novel Traditional Chinese Medicine (Liu-Wei-Di-Huang-Wan) Pellets Prepared by Extrusion-Spheronization Method

雖然傳統中草藥近來受到廣泛注目，其應用卻常因為缺乏完整藥劑學性質之研究而受到限制，本研究進行廣泛使用之中草藥－－六味地黃丸新劑型之探討。由於傳統中草藥含有許多成分以及複雜之製造程序，而對於其有效主成分與賦形劑之間的交互作用之研究卻很少。首先，本研究利用示差掃瞄卡計法（DSC），探討六味地黃丸主成分及三種中草藥製劑常用賦形劑之不可配伍性。此外，以擠壓搓圓方法製備六味地黃丸新圓粒劑型，並利用L16（215）直交實驗設計法，對不同變因進行全面性的探討。將製得之合適圓粒與常用之賦形劑HPMC壓製成錠劑，以探討六味地黃丸錠劑新劑型製備之可行性。最後，以23複因子設計來探討不同參數之圓粒及錠劑劑型之溶離曲線。本研究中製備之六味地黃丸圓粒呈現出良好的可壓縮性，經由壓錠過程形成較堅硬及緊密之結構，藥物有較緩慢之初始釋出速率，並得到更好之安定性。藉由改變擠壓搓圓過程之不同變因，可得到合適之六味地黃丸錠劑與圓粒劑型，這些新劑型可提供傳統中草藥在製備上另一種選擇。

Traditional Chinese Medicine (TCM) has received broader attention recently, but the applications are limited due to the lack of more complete study of their pharmaceutical properties. TCM often consists of numerous ingredients and generally involves a complicated manufacturing process, but studies on the interaction of the active ingredients and excipients are rare. In this study, the development of a novel dosage form of a widely utilized TCM (Liu-Wei-Di-Huang-Wan, LWDHW) was investigated. Firstly, Differential Scanning Calorimetry (DSC) was used to study the incompatibility between the active ingredients of LWDHW and three excipients commonly used in the manufacturing of TCM products. Secondly, a novel pellet dosage form of LWDHW was prepared using the extrusion-spheronization method, and L16 (215) orthogonal experimental design method was applied to perform an overall investigation of different variables. The frequently used excipient, hydroxypropyl methylcellulose (HPMC), was compressed with resultant optimal pellets to investigate the feasibility of a new LWDHW tablet dosage form. Finally, a 23 full factorial design was used in drug release studies to explore the dissolution profile of pellets and tablets at various parameters. The pellets prepared in this study exhibited good compression properties and formed a harder and tighter structure during the compression process, the resultant tablets showed a slower initial release rate and higher stability than pellets. Optimal LWDHW pellet and tablet dosage forms were obtained by adjusting the variables of the extrusion-spheronization process. The results from this study may provide a novel way of preparing LWDHW as well as other TCM dosage forms.