外消旋(R,S)-(±)-伊普鹽二水化合物的介晶質,成核與結晶成長; Mesocrystals, Nucleation and Crystal Growth of Racemic (R,S)-(±)-Sodium Ibuprofen Dihydrate

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Title:	外消旋(R,S)-(±)-伊普鹽二水化合物的介晶質,成核與結晶成長;Mesocrystals, Nucleation and Crystal Growth of Racemic (R,S)-(±)-Sodium Ibuprofen Dihydrate
Authors:	張瓊文;Chyong Wen
Contributors:	化學工程與材料工程研究所
Keywords:	硫酸十二酯鈉;伊普鹽二水化合物;mesocrystals;S)-(±)-Sodium Ibuprofen Dihydrate;solvent screening;Racemic (R;nucleation and crystal growth
Date:	2007-06-27
Issue Date:	2009-09-21 12:27:52 (UTC+8)
Publisher:	國立中央大學圖書館
Abstract:	在藥物的市場上，大約50%的藥物都是消旋性混合物 (racemic mixture)。消旋性混合物的種類有三種: 外消旋聚集物、外消旋混合物或者擬消旋體（固體溶液）。市面上大部分（90-95%）的外消旋藥都是外消旋混合物。在這篇論文中，我們集中在伊普鹽二水化合物的外消旋混合物藥的結晶。在本研究中有三個部份。首先，利用初步的溶劑篩選建立一個有關伊普鹽二水化合物的外消旋混合物結晶的資料庫，有溶解度、同質異相、結晶度和晶貌。Hansen parameters被利用來預測活性藥物份在不同的溶劑中的溶解度。第二，添加硫酸十二酯鈉在伊普鹽二水化合物的外消旋混合物的結晶中可以誘發介晶質的聚集並且具有良好的排列方向和外在的晶面。奈米顆粒可以自我組裝成介晶質而增加伊普鹽二水化合物的外消旋混合物的溶解速率。並且，添加硫酸十二酯鈉添加物可以誘發不同的同質異相並改變左右旋的比例。第三，我們使用電導度計來執行原位監控整個介晶質結晶過程並且整合熱力學與動力學的資訊來建立基本的成核和成長的參數。最後，所有的實驗都進行在伊普鹽二水化合物的外消旋混合物的臨界微胞濃度之上。 In the pharmaceutical market, approximately 50% are racemics (mixture of enantiomers). Racemic species have three types: racemic conglomerate, racemic compound and pseudoracemate. Most of the racemic drugs are racemic compound (90-95%). In this thesis, we focused on the crystallization of the racemic compound of (R,S)-(±)-sodium ibuprofen dihydrate. It has three sections in this study. Firstly, a useful engineering data bank of solubility, polymorph, crystallinity and crystal habits of racemic (R,S)-(±)-sodium ibuprofen dihydrate was established by initial solvent screening. Hansen parameters were utilized to predict APIs’ solubility in different solvents. Secondly, the presence of sodium dodecyl sulfate (SDS) additive in the crystallization of racemic (R,S)-(±)-sodium ibuprofen dihydrate could induce the formation of aggregation of mesocrystals which has well-aligned orientation and external crystal faces. Nanoparticles by self-assembly to form mesocrystals can enhance dissolution rate of racemic (R,S)-(±)-sodium ibuprofen dihydrate. Beside, the presence of the additive can induce different polymorphs and chance chiral resolution. Thirdly, conductivity in situ to monitor the entire crystallization process of mesocrystals and to gather the mesocrystals kinetic (nucleation and crystal growth) and thermodynamic (Gibbs free energy) information. The fundamental nucleation and crystal growth parameters were then estimated. Finally, all of the experiments were preceded above Critical Micelle Concentration (CMC) of racemic (R,S)-(±)-sodium ibuprofen dihydrate.
Appears in Collections:	[National Central University Department of Chemical & Materials Engineering] Electronic Thesis & Dissertation

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