New Category for Active Pharmaceutical Ingredients, a Low Molecular Weight Organogelator: Crystal Structure of Atorvastatin Calcium and Its Unusual Phase Transition Behavior during Dissolution

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• 作者：Bishal Raj Adhikari ; Daeyoung Kim ; Jae Ho Bae ; Jisun Yeon ; K. C. Roshan ; Sung Kwon Kang ; Eun Hee Lee
• 刊名：Crystal Growth & Design
• 出版年：2016
• 出版时间：December 7, 2016
• 年：2016
• 卷：16
• 期：12
• 页码：7198-7204
• 全文大小：519K
• ISSN：1528-7505

文摘

A gel is presented which represents a new category of pharmaceutical active ingredient in addition to the conventional crystalline and amorphous forms. The crystal structure of atorvastatin calcium ethylene glycol solvate suggests atorvastatin calcium to be a low-molecular weight organogelator that forms organogels with a wide variety of alkyl alcohols. Metal ion driven ionic interactions based on the amphiphilic nature of atorvastatin calcium leads to a lamellar type packing structure. Like ethylene glycol in its solvated form, alkyl alcohols, ranging from ethanol to octanol, can interact with the metal ions, and/or occupy the void spaces within that lamellar structure, thereby forming organogels featuring highly varying solubilities and unusual phase transition behaviors. An in situ dissolution study identified changes in the amounts/ratios of solvents in the atorvastatin calcium organogels without any significant structural changes, indicating that simultaneous solvent exchange is the mechanism of phase transition during dissolution. The presented low molecular gelator system may also be observed with the other statins that share common structural features with atorvastatin calcium as well as with other pharmaceutical materials. Thus, we propose a new form of active pharmaceutical ingredient, a gel. Since gels show important pharmaceutical properties quite distinct from those of crystalline or amorphous forms, they deserve special attention.