The effects of thermodynamics on mass transfer and enantioseparation of (R,S)-amlodipine across a hollow fiber supported liquid membrane Niti Sunsandee a , Natchanun Leepipatpiboon b,⇑ , Prakorn Ramakul c , Thidarat Wongsawa a , Ura Pancharoen a,⇑ a Department of Chemical Engineering, Faculty of Engineering, Chulalongkorn University, Bangkok 10330, Thailand b Chromatography and Separation Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University, Patumwan, Bangkok 10330, Thailand c Department of Chemical Engineering, Faculty of Engineering and Industrial Technology, Silpakorn University, Nakhon Pathom 73000, Thailand article info Article history: Received 6 May 2012 Received in revised form 16 September 2012 Accepted 26 September 2012 Available online 11 October 2012 Keywords: Thermodynamics Temperature effects Enantioseparation HFSLM (S)-amlodipine abstract Chiral separation of enantiomers of amlodipine, one of the most commonly prescribed antihypertensive drugs, was examined using the hollow fiber supported liquid membrane (HFSLM) extraction technique. The influence of temperature on enantioseparation of (R,S)-amlodipine via a HFSLM containing the chiral selector O,O 0 -dibenzoyl-(2S,3S)-tartaric acid ((+)-DBTA) was systematically investigated. The parameters affecting the mass transfer such as distribution ratio and flux were determined at different temperatures ranging from 278.15 K to 313.15 K. The thermodynamic parameters, DH and DG, were determined, and an interesting relationship with stoichiometric value was found: higher temperatures lead to an increase in distribution ratio but a decrease in enantioselectivity. The activation energy (E a ) of the (S)-amlodipine extraction reaction was 71.10 kJ/mol. The chemical reaction between (S)-amlodipine and (+)-DBTA is the mass transfer-controlling step for the enantioseparation of (S)-amlodipine by a hollow fiber supported liquid membrane system. Ó 2012 Elsevier B.V. All rights reserved. 1. Introduction Amlodipine – 3-ethyl 5-methyl-2-[(-2-(aminoethoxymethyl]-4- (2-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylate (Fig. 1) – is a potent third-generation dihydropyridine derivative calcium channel blocker used in the treatment of hypertension and angina pectoris [1]. Like most other calcium blocker agents of the dihydropyridine type, amlodipine is therapeutically used as a racemic mixture. However, the vasodilating effect only resides in (S)-amlodipine [2].(R)-amlodipine is inactive, and is thought to be responsible for pedal edema observed with racemic amlodipine [3].(S)-amlodipine is the more potent calcium channel blocker showing about 2000 times the potency in in vitro evaluation in the rat aorta than (R)-amlodipine [4]. In addition to its longer dura- tion of action, (S)-amlodipine reduces the chances of reflex tachy- cardia, and its clearance is subject to much less inter-subject variation than (R)-amlodipine [5]. Several methods dedicated to the separation of enantiomers of amlodipine have been reported [6]. Separation techniques such as crystallization [7], chromatography [8] and capillary electrophore- sis [9] have been developed. These techniques have furthered re- search and development into the separation of (S)-amlodipine from its racemic mixture; however, there are some deficiencies. Crystallization requires many time-consuming and cost-inefficient steps [10]. Chromatography and capillary electrophoresis are not suitable for production of multi-gram-quantities [11]. Membrane extraction is one of the separation processes, which combines li- quid–liquid extraction [12–16] with a membrane [17]. The litera- ture on enantioselective liquid–liquid extraction spans more than half a century of research [18–21]. Enantioseparation through li- quid membranes was first reported in the 1970s [22]. Recently, enantioselection by membrane-supported liquid–liquid extraction has been a technology of interest for chemical engineers in a wide range of fields, such as fine chemicals, pharmaceuticals and foods [23–25]. Hollow fiber supported liquid membrane (HFSLM) extrac- tion is an especially popular technique. Great progress has been made in such applications, as in metal ion extraction [26,27], or- ganic extraction [28], pharmaceutical extraction [29], and enzy- matic transformation [30]. In recent years, racemic separation by HFSLM has proven to be a topic of great interest [31,32]. HFSLM is renowned as an effective method for simultaneous extraction and recovery of compounds from very dilute solutions of a component of interest in the feed by a single unit operation [33]. The advantages of the hollow fiber contactor over traditional separation techniques include lower capital and operating costs 1383-5866/$ - see front matter Ó 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.seppur.2012.09.027 ⇑ Corresponding authors. Tel.: +66 2218 7608; fax: +66 2254 1309 (N. Lee- pipatpiboon), tel.: +66 2218 6891; fax: +66 2218 6877 (U. Pancharoen). E-mail addresses: natchanun.l@chula.ac.th (N. Leepipatpiboon), ura.p@chu- la.ac.th (U. Pancharoen). Separation and Purification Technology 102 (2013) 50–61 Contents lists available at SciVerse ScienceDirect Separation and Purification Technology journal homepage: www.elsevier.com/locate/seppur