(321g) The Impact of Reaction and Crystallization of Acetaminophen (Paracetamol) on Filtration and Drying through in-Process Controls
AIChE Annual Meeting
2014
2014 AIChE Annual Meeting
Process Development Division
Crystallization Process Development
Tuesday, November 18, 2014 - 2:35pm to 2:55pm
abstract example
The Impact of Reaction and Crystallization of Acetaminophen
(Paracetamol) on Filtration and Drying through In-Process Controls
Hung Lin Lee, Hong Yu Lin, and Tu Lee?
Department of Chemical and Materials Engineering, National Central University,
300 Jhong-Da Road, Jhong-Li City 320, Taiwan R.O.C.
ABSTRACT
Acetaminophen (paracetamol), one of the important analgesic and antipyretic active pharmaceutical ingredients (APIs), is synthesized via acetylating
p-aminophenol with acetic anhydride. To understand how reaction and crystallization affect the solid-state properties of acetaminophen, and influence the downstream operations, three crystallization routes (i.e. Cases I, II, and III) with various modes in agitation and addition of sodium hydroxide have been studied from the chemical engineering point of view. The three extreme cases are designed to explore the effect of particle size distribution (PSD) on filtration and drying. The thorough processes involving concentration profile, temperature, and pH value, are monitored by in-process controls such as UV-vis spectrophotometer, thermocouple
and pH papers, respectively. The overall mass balances are compiled and reveal that yields and purities of acetaminophen obtained in three cases are almost the same from chemistry point of view. The nucleation and crystal growth rates are calculated by the mixed-suspension, mixed-product removal (MSMPR) formalism as well. This study demonstrates that the three crystallization processes with different PSD gives various distinctive processing properties of acetaminophen such as cake resistance
and Krischer rate-moisture plot in solid state. Although the controls of purities and
? Corresponding author. Telephone: +886-3-422-7151 ext. 34204. Fax: + 886-3-425-2296. E-mail: tulee@cc.ncu.edu.tw
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yields have been achieved in the chemical reaction, the three extreme cases with various crystallization routes as models for designing a process operation based on subsequent applications have been studied. To design a robust and reproducible process, all of the processing and functional properties must be taken into a consideration.
Keywords: Acetaminophen, in-process controls, crystallization routes, unit operations.
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