Spherical Crystallization for Lean Solid-Dose Manufacturing by Initial Solvent Screening: The Study of Cimetidine

• Main Authors: Hung-ju Hou, 侯宏儒
• Other Authors: Tu Lee
• Format: Others
• Language: en_US
• Online Access: http://ndltd.ncl.edu.tw/handle/29416550033383174513

碩士 === 國立中央大學 === 化學工程與材料工程研究所 === 96 === Drug discovery and development process is a long and expensive process. The average cost of a new drug from laboratory to market is about US$500 to US$880 million and it takes ten to fifteen years to complete all the processes. Three important studies in this thesis were performed to improve the efficiency of the discovery and development process. Firstly, a useful engineering data bank of solubility, polymorphism, crystal habits and crystallinity by solvent screening for cimetidine would be established and a robust, miniature solvent screening method would be introduced. Secondly, a spherical crystallization technique replaces the traditional wet granulation for lean solid-dose manufacturing. This technique could be used to increase the flowability of active pharmaceutical ingredient (API) and save the money and time of solid-dose manufacturing. Thirdly, we used the Form Space to find the possible three-solvent combinations for spherical crystallization. Choosing the possible three-solvent combinations method for spherical crystallization is not clear. In this thesis, the Form Space was used to make the search of the possible three-solvent combinations more systematic and easy. Cimetidine was chosen as the active pharmaceutical ingredient because of its abundance in literatures. But the investigation methods in this thesis could also be applied to some other APIs or drug candidates or simple organic materials.