Engineering Reaction and Crystallization and the Impact on Filtration, Drying, and Dissolution Behaviors: The Study of Acetaminophen (Paracetamol) by In-Process Controls

被引：26

作者：

Lee, Tu ^{[1
]}

Lin, Hong Yu ^{[1
]}

Lee, Hung Lin ^{[1
]}

机构：

[1] Natl Cent Univ, Dept Chem & Mat Engn, Jhong Li City 320, Taiwan

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2013年 / 17卷 / 09期

关键词：

BATCH CRYSTALLIZATION; DIRECT COMPRESSION; PURE PARACETAMOL; SCALE-UP; FORM-II; POLYMORPH; KINETICS; CRYSTALS; AGGLOMERATION; DYNAMICS;

D O I：

10.1021/op400129n

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

Acetaminophen was synthesized by reacting p-aminophenol with acetic anhydride. Overall materials balance was compiled. Three different crystallization paths (i.e., cases I, II, and III) involving various modes in agitation and addition of sodium hydroxide were taken to produce acetaminophen particles with different particle size distributions (PSDs) and polymorphism. The concentration profile of acetaminophen, temperature, and pH values throughout reaction and crystallization were monitored mainly by in-process control (IPC). The rates of nucleation, crystal growth, and agglomeration during crystallization were quantified by the mixed-suspension mixed-product removal (MSMPR) formalism. The average specific cake resistance for filtration, Krischer rate-moisture plot for drying, Carr's index for powder flowability, and dissolution rate for drug delivery of acetaminophen crystals generated in cases I, II, and III were thoroughly studied and compared.

引用

页码：1168 / 1178

页数：11

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