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

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 (2^15) 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 2^3 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.