Membrane-based extraction of cholesterol lowering drug: Effect of membrane type on extraction

Separation and Purification Technology 46 (2005) 63–71

Membrane-based extraction of cholesterol lowering drug: Effect of membrane type on extraction Tippabust Eksangsri a,∗ , Hiroaki Habaki b , Junjiro Kawasaki b b

a Chemical Engineering Department, Faculty of Engineering, Thammasat University Rangsit Campus, Pathumthani 12120, Thailand Graduate School of Science and Engineering, Department of Chemical Engineering, Tokyo Institute of Technology, Meguro-ku, Tokyo 152-8552, Japan

Received 16 September 2004; received in revised form 17 January 2005; accepted 30 April 2005

Abstract Compactin (ML-236B) is an effective ingredient for production of anti-hypolipidemia medicine called mevalotin (Sankyo Pharmaceutical Co. Ltd.). Conventional liquid–liquid extraction is now applied in the commercial process of purification and concentration of compactin. In this study, we investigated compactin extraction process from aqueous solution to organic solvent of ethyl acetate using a microporous membrane-based flat interface contactor. Teflon (polytetrafluoroethelene; PTFE) membranes with 0.1 ␮m pore size with either hydrophilic or lipophilic surface were utilized under the study. The extraction experiments were conducted at 298 K. The main objective of this study was to investigate mass transfer characteristics of compactin extraction by different types of membranes at the same operating conditions. Our previous work showed that water and ethyl acetate transferred simultaneously with compactin during the extraction. Therefore, the study of mass transfer in a binary mixture of two solvents was indispensable. Local mass transfer coefficients of extraction could be estimated from the mass transfer of binary mixture, and mass transfer models for membrane extraction were developed. These mass transfer coefficients and models can be applied to any operating conditions. We found that extraction of compactin by lipophilic membrane has better performance than the extraction with hydrophilic membrane due to the faster transfer of ethyl acetate relative to water. © 2005 Elsevier B.V. All rights reserved. Keywords: Membrane-based extraction; Compactin; Hydrophilic membrane; Lipophilic membrane; Local mass transfer coefficients; Mass transfer models

1. Introduction Compactin is highly effective in lowering cholesterol synthesized in liver. Its mechanism is to inhibit the activity of HMG-CoA reductase, the enzyme that promotes cholesterol synthesis. Discovered in 1976 [1], continuous development of compactin synthesis brought out the famous “statin” drugs which are on huge demand for patients around the world [2]. In the commercial production, compactin is isolated from the cultures of Penicillium citrinum and used as an intermediate for production of mevalotin (Sankyo Pharmaceutical Co. Ltd.), the bestseller cholesterol lowering drug in Japan [3]. Production patent of mevalotin was expired in late 2003 while its demand is still large. Generic drug on the same class will eventually emerge and the marketing will be very ∗

Corresponding author. E-mail address: [email protected] (T. Eksangsri).

1383-5866/$ – see front matter © 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.seppur.2005.04.010

competitive. Similar to other pharmaceutical production, the main expense in manufacturing of pravastatin is from the concentration and purification processes rather than the synthesizing ones. However, there is a lack of understanding on the main concentration process, i.e. extraction of compactin. The extraction unit used in commercial process is mixing and settling type. It is a classical type used in medicine production but its mass transfer behavior is very complicated due to the turbulence at liquid–liquid interface. True shape of interface is hard to predict in mixing and settling tank so the effective contacting surface cannot be identified. Two types of PTFE membrane were used in our study. One was hydrophilic membrane and another was lipophilic membrane. The difference of these two membranes was type of solvent filled inside their pores due to their surface selectivity. Aqueous solution filled up the hydrophilic pores while organic solvent filled up the lipophilic pores. Adsorption of the solute on membrane surface can be neglected even at such

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Nomenclature Ci.j Dij Ka • ki,j mi Ni z xi,p z yi,p

concentration of component i in phase j (kmol/m3 ) diffusivity coefficient of solute i in j phase (m2 /min) dissociation constant (kmol/m3 ) mass transfer coefficient of component i in j phase (kmol/m2 min) distribution coefficient of component i (–) transfer flux of component i (kmol/m2 min) mole fraction of component i in aqueous phase at location p, of z-type contactor (–) mole fraction of component i in organic phase at location p, of z-type contactor (–)

Greek letters δ membrane thickness (␮m) ε membrane porosity (–) ηj viscosity of liquid j (cP) νj kinematic viscosity of liquid j (m2 /s) density of liquid j (kg/m3 ) ρj τ pore tortuosity (–) ωj liquid velocity (rpm) Superscripts z type of membrane-based contactor Subscripts A compactin anion aq aqueous phase E extract phase E ethyl acetate E2 the end of extract phase adjacent to membrane H hydrophilic membrane HA compactin free acid L lipophilic membrane M total compactin, i.e. compactin free acid plus compactin anion M1 the end of membrane adjacent to raffinate phase M2 the end of membrane adjacent to extract phase org organic phase p position along the transfer coordinate (m) R raffinate phase R1 the end of raffinate phase adjacent to membrane t total W water

a small pore size since the size of compactin molecule is much smaller. Ishizu et al. [4] used the same kind of membrane for their study on liquid membrane extraction of compactin and reported no adverse effect of adsorption. This membrane-

based contactor is considered suitable for our study because it provides less disturbed interfacial area of aqueous and organic phases during extraction. Other types of contactors such as spray tower or packed column will cause more disturbing interface relative to the membrane-based contactor. The organic solvent used in this study was ethyl acetate, the same as used in commercial plant. Although ethyl acetate gives high distribution of compactin, it poses another serious trouble from its ability to solve in aqueous solution. Compactin is an amphiphatic molecule. It can be solved in either aqueous solution or organic solvent since it has both hydrophilic and hydrophobic groups in one molecule. As a result, an increase in concentration of compactin causes salting effect in water–ethyl acetate system by increasing water solubility in organic solvent and increasing ethyl acetate solubility in aqueous solution when its concentration increases. These, in consequence, cause simultaneous transfer of water and ethyl acetate during compactin extraction [5]. The objective of this study is to investigate the extraction characteristics of compactin in water–ethyl acetate system, in a membrane-based contactor. A comparison of two kinds of membrane used is conducted. Mass transfer models of compactin under the mutual solubility change of the two solvents were developed in this work. At the final stage, mass transfer coefficients of extraction process are obtained.

2. Equilibrium of compactin in water–ethyl acetate system Compactin is a weak acid so it dissociates in aqueous solution. Among a few forms of compactin in aqueous solution, only compactin free molecule can permeate into organic solvent. Compactin extraction from aqueous phase to organic phase and reversed extraction can be controlled by pH adjustment. In this study, the initials HA, A and H denote to free compactin, ionic compactin and proton, respectively. The dissociation of compactin in aqueous solution can be written as Eq. (1), while the dissociation in organic solvent is assumed non-existent. CH,aq CA,aq Ka = (1) CHA,aq where Ka is dissociation constant of compactin and Ci,aq is concentration of component i in aqueous solution. Distribution of compactin in water–ethyl acetate system can be written in a form of a distribution coefficient in Eq. (2). mHA =

CHA,E CHA,R

(2)

where mHA is distribution coefficient of compactin, CHA,j the concentration of compactin in j phase, R the raffinate phase and E is the extract phase. Our earlier study on equilibrium of compactin in water–ethyl acetate at 298 K [5] shows that compactin con-

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centration is important in determination of Ka and mHA . In a range of compactin concentration of the study, it is assumed that the effective dissociation constant (Ka ) is constant; 1.0 × 10−8 kmol/m3 . This estimated Ka is so small that we can assume a non-dissociation of compactin in our study. Distribution coefficient of compactin could be well correlated to compactin concentration in aqueous solution, as written in Eq. (3). −0.69 mHA = 0.028CHA,aq

(3)

The distribution of compactin is very small when compactin concentration is large due to the increase of mutual solubility of the two solvents. Although compactin selectivity is high in organic solvent, it cannot compete with that of water or ethyl acetate. Our earlier studies [5,6] show the relationship of water concentration and compactin concentration in organic phase and the relationship of ethyl acetate concentration and compactin concentration in aqueous phase at equilibrium as in Eqs. (4) and (5):
0  CW,org log = −1.20 × 10−3 − 19.48CM,org CW,org 2 −508.25CM,org


log

0 CE,aq

CE,aq

(4)

 2 = 8.00 × 10−4 + 0.43CM,aq − 8.24CM,aq

Fig. 1. Illustration of mass transfer in membrane-based contactor for binary two-phase system of water and ethyl acetate.

(5) 0 is the saturated concentration of component i in j where Ci,j phase of binary two-phase system at 298 K; components: W is water, E the ethyl acetate, M is total compactin. Other than obstructing the distribution of compactin, the increase of solvents mutual solubility also causes undesirable dispersion of water and ethyl acetate. Compactin possess surfactant nature that it stabilizes emulsion. So it takes a long time to completely separate two phases of solvents. These are disadvantages of using ethyl acetate as an extraction solvent. However, it is not a favorable task for the producers to change chemicals used in existing process. Safety and economic issues should also be concerned of, and the process of change regarding permission request to an authorized institute is tedious. At the moment, we believe ethyl acetate is still a suitable solvent for extraction purpose.

3. Mass transfer of water and ethyl acetate in binary two-phase system In binary two-phase system, equilibrium conditions at the interface between aqueous and organic phases are always existed. These conditions are invariant at constant temperature and pressure. In a hydrophilic membrane-based contactor as illustrated in Fig. 1(a), the true interface is located at M2/E2. The true interface between aqueous and organic phases in

lipophilic membrane-based contactor is located at R1/M1, as shown in Fig. 1(b). With available concentration in bulk liquid and equilibrium concentrations of water, mass transfer coefficients in liquid film can be obtained. In hydrophilic membrane-based contactor, mass transfer in aqueous side is a combination of transfer in raffinate and membrane. On the contrary, only mass transfer in raffinate phase contributes to mass transfer in aqueous side of lipophilic membrane-based contactor. To obtain mass transfer coefficient in raffinate film, lipophilic membrane-based contactor should be used. The same explanation can be utilized for determination of mass transfer coefficient in extract film. Hydrophilic membrane-based contactor should be used for that purpose. We assumed that mass transfer coefficients in liquid films were equal no matter which type of membrane was applied to the contactor. Mass transfer coefficients of water in raffinate and extract films can be calculated by Eqs. (6) and (7). kR• = kE• =

L − xL N L NW W,R t L L xW,R − xW,R1 H − yH H NW W,E2 Nt H H yW,E2 − yW,E

(6)

(7)

where kR• is the mass transfer coefficient in raffinate film (kmol/m2 min), kE• the mass transfer coefficient in extract film

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z (kmol/m2 min), xW,j the mole fraction of water in aqueous z solution at location j in z membrane-based contactor, yW,j the mole fraction of water in organic solvent at location j in z z membrane-based contactor, NW the transfer flux of water by z membrane-based contactor (kmol/m2 min), NEz the transfer flux of ethyl acetate (kmol/m2 min), Ntz the total transfer flux z of liquid (kmol/m2 min) = NW + NEz . Our recent study of mutual solubility of water and ethyl acetate at 25 ◦ C [5,6] gave us the mole fraction of each compound at equilibrium. For hydrophilic membrane-based contactor:

At location M2/E2,

H xW,M2 = 0.9825 H yW,E2 = 0.1692

For lipophilic membrane-based contactor: At location R1/M1,

L xW,R1 = 0.9825 L yW,M1 = 0.1692

Concentrations of water and ethyl acetate at the interface between liquid and membrane can be measured only at the true interface of aqueous and organic solutions. At the location between raffinate phase and membrane in hydrophilic membrane-based contactor (R1/M1) and the location between membrane and extract phase in lipophilic membranebased contactor (M2/E2), measurement of water and ethyl acetate content are impossible. However, those concentration can be calculated by the used of mass transfer coefficients obtained by Eqs. (6) and (7), assuming kR• and kE• are equal for both types of contactor. Once the concentrations at two ends of membranes are found, mass transfer coefficients in membrane can be estimated by Eq. (8). • kM,z =

z z NW − xW,M1 Ntz

z z (xW,M1 − xW,M2 )

(8)

• when kM,z is the mass transfer coefficient in z membrane (kmol/m2 min).

4. Mass transfer of compactin in ternary system With compactin presiding, the equilibrium of ternary system needs to be adjusted to accommodate the existence of the three components. We knew from the equilibrium study that the three components transfer simultaneously in the same direction when compactin is extracted from aqueous to organic phase. Mass transfer configurations of compactin, water and ethyl acetate in hydrophilic membrane-based contactor and lipophilic membrane-based contactor are demonstrated in Fig. 2(a and b), respectively. Compactin concentration in ternary system is very small relative to concentrations of the two solvents. This implies that the local mass transfer coefficients of water in ternary system are the same as those obtained in binary system. Thus, the mass transfer coefficients of compactin can be estimated

Fig. 2. Illustration of mass transfer in membrane-based contactor for ternary system. • and k • of water. In order to from the modification of kR• , kM E modify mass transfer coefficients, Levich’s model [7] in Eq. (9) is selected.  −1/6 2/3 ρj • ωj 1/2 (9) ki,j ∝ Di,j ηj

where D is the diffusivity coefficient of component i in solvent j (m2 /min), ρ the liquid density (kg/m3 ), η the liquid viscosity (cp) and ω is the liquid velocity (rpm). Net transfer flux of compactin can be written as a summation of diffusional flux and flux caused by convective flow in a form [8]: NHA = −cD

dxHA + xHA Nt dz

or • (xHA,z1 − xHA,z2 ) + xHA Nt NHA = kHA

(10)

where NHA is the net transfer flux of compactin • is the mass transfer coefficient of (kmol/m2 min) and kHA 2 compactin (kmol/m min). Rate equations of compactin transfer in raffinate phase, membrane and extract phase for both types of membranebased contactor can be written in Eqs. (11)–(14), respectively. In raffinate phase: • NHA = kHA,R (xHA,R − xHA,R1 ) + xHA,R Nt

(11)

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Fig. 3. Configuration of membrane-based contactor.

5. Experiments

In membranes: Hydrophilic membrane, • NHA = kHA,MH (xHA,M1 − xHA,M2 ) + xHA,M1 Nt

(12)

Lipophilic membrane, • NHA = kHA,ML (yHA,M1 − yHA,M2 ) + yHA,M1 Nt

(13)

In extract phase: • (yHA,E2 − yHA,E ) + yHA,E2 Nt NHA = kHA,ML

(14)

With steady state operation, Eq. (11) = Eq. (12) = Eq. (14) for hydrophilic membrane extraction, while Eq. (11) = Eq. (13) = Eq. (14) for lipophilic membrane extraction. Basu and Sirkar [9] estimated mass transfer coefficient in membrane by its physical properties as: • kM =

εcD δτ

(15)

where ε is the membrane porosity, c the total concentration (kmol/m3 ), δ the membrane thickness (m) and τ is the membrane tortuosity. Comparison between this relationship and our experimental results is discussed later in Section 6.

Mass transfer fluxes of interested compounds were measured by the use of membrane-based contactor shown in Fig. 3. Two cylindrical glass cells of 120 ml volume were coupled together horizontally with a selected membrane placed in the middle. A stirrer is inserted inside each cell to assure the homogeneous solution. Flat interface between two bulks liquid was provided either by PTFE hydrophilic membrane (Advantec) or PTFE lipophilic membrane made (Advantec). The PTFE membrane is a porous membrane with pore size of 0.1 ␮m. Its microstructure is fibrous. Selective solvent will fill up the membrane’s pores and provide a layer of liquid film. Physical properties of membranes are summarized in Table 1. Morphology of membranes are shown in Fig. 3. Pictures of membranes were taken by JEOL SEM-6301F with gold coat and argon as inert gas. The experimental temperature was controlled at 298 K by the use of water tube winding Table 1 Specification of microporous membranes used under the study Specification

Hydrophilic membrane

Lipophilic membrane

Material Pore size (␮m) Thickness (␮m) Porosity

PTFE 0.1 35 0.71

PTFE 0.1 70 0.68

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around the contactor. The rotational speeds of stirrers in both cells were adjustable. 5.1. Mass transfer of water and ethyl acetate in binary, two-phase system Hydrophilic membrane was immersed in de-ionized water and lipophilic membrane was immersed in ethyl acetate before assembling to the contactor shown in Fig. 3. Only one type of membrane was used for one experiment. De-ionized water was filled in one cell of membrane-based contactor while 99.5% (v/v) ethyl acetate was filled in another. Agitation speeds of both cells were fixed at 200 rpm. Constant temperature of 298 K was controlled by the used of water tube winding around the contactor. Samples from both cells were taken at certain time interval within 60 min. Water and ethyl acetate concentrations were analyzed by GC-8A (Shimadzu Corporation). Acetone was used as diluent and helium gas was used as carrier. The gas chromatography was operated in TCD mode with column temperature of 150 ◦ C and current of 90 mA.

Fig. 4. Concentration profiles of ethyl acetate in aqueous solution and water in organic solvent obtained from membrane-based extraction.

5.2. Mass transfer of compactin in ternary system Before each extraction experiment, compactin aqueous solution was saturated with ethyl acetate and ethyl acetate was saturated with de-ionized water. The saturation method was to add the second liquid into main solution until the first drop of separated second liquid appeared. The pH of aqueous feed solution was adjusted to 6 afterward. These aqueous solution and organic solvent were brought into contact in membranebased contactor prepared by the same method for experiment in Section 5.1. Hydrophilic membrane and lipophilic membrane were used one at a time, under the same feed conditions (CM,0 = 0.2 kmol/m3 at pH 6) and agitation speed of 200 rpm. Samples from both cells were taken at certain time interval within 60 min. Compactin concentrations were analyzed by HPLC (Shimadzu Corporation) while water and ethyl acetate concentrations were analyzed by GC-8A (Shimadzu Corporation). A solution of 75% (v/v) methanol was used as diluent for HPLC analysis. The carrier was a mixture of methanol 75% (v/v), triethylamine 0.1% (v/v) and acetic acid 0.1% (v/v) in de-ionized water. HPLC column was packed with silica gel and operated at temperature 30 ◦ C.

Fig. 5. Transfer fluxes of water and ethyl acetate from extraction by hydrophilic membrane-based contactor.

ethyl acetate phase increases faster when lipophilic membranes were used. Figs. 5 and 6 shows the transfer fluxes of water and ethyl acetate obtained from each type of contactor. They show that mass transfer in hydrophilic membrane is different from mass transfer in lipophilic membrane. Water moved faster through hydrophilic membrane so the total transfer flux followed the transfer direction of water. In contrary, ethyl acetate moved faster through lipophilic membrane; therefore, the direction of the total flux transferred is in the same direction of ethyl acetate transferred. A positive sign indicates a transfer flux from aqueous to organic phase, and a negative sign to transfer flux from organic to aqueous phase.

6. Results and discussion 6.1. Mass transfer of water and ethyl acetate in binary, two-phase system Fig. 4 shows the extraction results of binary mixture by hydrophilic membrane-based contactor and lipophilic membrane-based. It verifies the natures of the membranes. Concentration of water in extract phase increases faster when hydrophilic membranes were applied, while concentration of

Fig. 6. Transfer fluxes of water and ethyl acetate from extraction by lipophilic membrane-based contactor.

T. Eksangsri et al. / Separation and Purification Technology 46 (2005) 63–71

In hydrophilic membrane-based contactor: N t = NW − N E

(16)

In lipophilic membrane-based contactor: −Nt = NW − NE

(17)

Mass transfer coefficient in extract film, kE• , was calculated from the result of hydrophilic membrane extraction. At the same time, mass transfer coefficient in extract film, kR• , was calculated from the result of lipophilic membrane extraction. Average values of these mass transfer coefficients are shown below. kE• = 0.040 kmol/m2 min

(18)

kR• = 0.091 kmol/m2 min

(19)

Then the concentration of water and ethyl acetate at M1 in hydrophilic membrane-based contactor and those concentrations at M2 in lipophilic membrane-based contactor were calculated by the use of estimated kE• and kR• in Eqs. (18) and (19). Once concentrations at the two ends of membrane were known, mass transfer coefficients in membranes could be calculated. We found that: • kMH = 0.078 kmol/m2 min

(20)

• kML

(21)

= 0.012 kmol/m min 2

• and k • by membranes’ properties, one If one estimated kMH ML • • around 10, which is only 20% : kML will get a ratio of kMH deviation from the ratio we obtained by our experimental results. This closeness of the two ratios obtained from different method supports the credibility of our study. Physical properties of liquids in binary mixtures can be used to estimate ratio of mass transfer coefficient in liquid films, by Eq. (9). The ratio of diffusivity coefficient is 1 since it is a binary mixture. Therefore, the ratio of the two mass transfer coefficients depends only on ratio of kinematic viscosity of the liquids. It came out that kR• : kE• = 1.11, which is quite different from the number we obtained from experiment; kR• : kE• = 2.25. A clear reason of such difference could not be found at the moment. Using a flat membrane as a mean for liquids contact should allow the interface of two-phase system more conforming compared to the use of packed bed or spray tower, although not perfectly flat. The morphology of PTFE membrane is fibrous. The macroscopic interface can be reasonably treated flat but the microscopic view might be not. Unidentified true shape of the liquid–liquid interface provided by membrane, as well as capillary effect caused by surface property of the liquids themselves, might cause the true length diffusional path to be shorter or longer than the membrane thickness. Furthermore, the membrane thickness under this study is as small as 35 ␮m (hydrophilic membrane) or 70 ␮m (lipophilic membrane). If there was a movement of 10 ␮m of the interface caused by the membrane morphology and liquid surface property as mentioned earlier, this minuscule movement

69

would cause more than 15–30% deviation from the estimated mass transfer coefficients. This phenomenal effect is out of the reach for any research to clarify, and we do not think it is necessary to find out. However, these two mass transfer • in a later stage. It was coefficients were used to evaluate kM • from experiment and obtained k • found that obtained kM M from simple calculation by membrane’s physical properties were surprisingly comparable. This agreement may be used as a proof that the estimated kR• and kE• are reliable. 6.2. Mass transfer of compactin in ternary system Fig. 7 plots the extent of compactin, water and ethyl acetate concentrations from extraction in membrane-based contactor. We can see that the system is almost equivalent to the binary system of water and ethyl acetate since the compactin concentrations were very small relative to water and ethyl acetate concentrations. The concentration ratio of water and compactin in aqueous phase was about 800 times and concentration ratio of ethyl acetate and compactin in organic phase was more than 10,000 times. According to the equilibrium study, water solubility in organic phase increased and ethyl acetate solubility in aqueous phase decreased due to the compactin concentration transferred from aqueous to organic bulk. This caused the same direction transfer for all components from aqueous to organic phase. It is clear that compactin transfers not only by its diffusion but also is carried by the movement of water and ethyl acetate.

Fig. 7. Concentration profiles of compactin, water and ethyl acetate from extraction in membrane-based contactor.

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From the results, our work shows two main concepts: (1) The amount of compactin is so small that there is no significant effect on water and ethyl acetate transfer. (2) Although the transfer characteristics of water and ethyl acetate are independent of compactin, the equilibrium between water and ethyl acetate was proved affected by compactin.

and steady-state condition of compactin transfer from membrane to extract phase At M2/E2,

xHA,M2 = xHA,E2

(29)

Providing that mass transfer coefficients in each phase and bulk concentrations were known, we have xHA,M1 =

• mHA (kHA,R xHA,R − NHA + Nt xHA,R )

kR•

(30)

Since compactin concentration is very small and so is compactin transfer flux when they are compared to those of water and ethyl acetate, total liquid flux can be thought of approximated as the summation of solvent fluxes only:

xHA,M2 = xHA,E2 =

Nt = NW + NE + NHA ∼ = NW + NE

Putting Eq. (30) and (31) into Eq. (13), total transfer flux could be obtained.

(22)

For hydrophilic membrane extraction, Eqs. (11) and (14) were rearranged. Steady-state condition of compactin transfer from raffinate to membrane was applied. At R1/M1,

xHA,R1 = xHA,M1

(23)

Equilibrium condition at the interface of membrane and extract phase was applied. At M2/E2,

xHA,E2 = mHA xHA,M2

(24)

Providing that mass transfer coefficients in each phase and bulk concentrations were known, xHA,M1 = xHA,R1 = xHA,M2 =

1 mHA



• kHA,R xHA,R − NHA + Nt xHA,R

kE• xHA,E + NHA kE• + Nt

kR• 

(25) (26)

Putting Eqs. (25) and (26) into Eq. (12), total transfer flux could be obtained. αNt3 + βNt2 + γNt + ξ = 0

(27)

kE• xHA,E + NHA kE• + Nt

αNt3 + βNt2 + γNt + ξ = 0

(31)

(32)

where α = mHA • • • β = mHA {(kHA,R + kHA,M + kHA,E )xHA,R − NHA }



• • • • γ = mHA (kHA,R kHA,M + kHA,M kHA,E • • +kHA,R kHA,E )xHA,R    • k • • NHA − HA,R + kHA,M + kHA,E mHA • • • ξ = (mHA xHA,R − xHA,E )kHA,R kHA,M kHA,E • • • • • • −(kHA,R kHA,E + kHA,M kHA,E + kHA,M kHA,R )NHA

Eqs. (27) and (32) are polynomial of order 3. However, the calculation gave only one root of real number while the rest were imaginary numbers. Therefore, total fluxes and interfacial concentrations of each experiment could be calculated.

where 6.3. Effect of membrane type on compactin extraction

α = mHA xHA,R • • • β = mHA {(kHA,R + kHA,M + kHA,E )xHA,R − NHA } • • • • • • γ = mHA {(kHA,R kHA,M + kHA,M kHA,E + kHA,R kHA,E )xHA,R • • • −(kHA,R + kHA,M + kHA,E )NHA } • • • • ξ = (−mHA (kHA,R kHA,E + kHA,M kHA,E ) • • −kHA,M kHA,R )NHA • • • −(xHA,E − mHA xHA,R )kHA,R kHA,M kHA,E

The same was done with lipophilic membrane extraction, with equilibrium condition at interface of raffinate phase and membrane: At R1/M1,

xHA,M1 = mHA xHA,R1

(28)

Mass transfer models were applied to the extraction of 0.2 M compactin aqueous solution at pH 6 and agitation speed of 200 rpm, with both types of membrane. The results will be discussed with the use of Fig. 8. With compactin presence, total fluxes from extractions by both types of membrane had positive sign. It means ethyl acetate solubility in aqueous phase decreased sharply so its total transfer was from raffinate to extract phase even in lipophilic membrane-based contactor. However, Nt of lipophilic membrane extraction was smaller than that of hydrophilic membrane extraction because of the nature of ethyl acetate flow described in the part of binary system extraction. Net transfer flux of compactin obtained from lipophilic membrane extraction was higher than that obtained from hydrophilic membrane extraction at the early stage of the operation. Since net transfer consists of diffusional transfer (Ndiff )

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Fig. 8. Transfer fluxes by extraction in both types of membrane-base contactor.

and bulk transfer (Nbulk ), these two transfer fluxes were evaluated separately by the usage of mass transfer models developed in Eqs. (27) and (32). It is unexpectedly found that Ndiff in both types of membrane were negative. Other than that, Ndiff in raffinate and extract films from hydrophilic membrane extraction were negative as well. These results imply that extraction of compactin by hydrophilic membrane was possible due to the movement of solvents only. In lipophilic membrane, Ndiff in raffinate and extract films were positive. These are major distinction between extractions by two types of membrane, and they show why extraction by lipophilic membrane gave higher performance than extraction by hydrophilic membrane. We might as well say that mass transfer in organic phase controlled the extraction since the film was extended when lipophilic was applied and it provided better performance.

7. Conclusions This study investigates a process of compactin extraction by the use of membrane-based contactor. Solvents of the extraction system are very important because they were the main components that transfer during the extraction and carry compactin through the interfaces. Local mass transfer coefficients in raffinate and extract phases of the extraction process were estimated for two types of membrane. Consequently, mass transfer coefficients in membranes were determined. Mass transfer models of compactin extractions were developed and the compactin concentration at the interfaces as well as total transfer flux could be calculated provided that

the local mass transfer coefficients were available. Therefore, mass transfer fluxes from diffusion and from convective flow were able to calculated separately. We could use these models to identify the different mechanism of extraction in two types of membrane. It is shown that lipophilic membrane extraction gave better extraction performance than hydrophilic membrane extraction.

Acknowledgements The authors would like to thank Sankyo Co. Ltd. for providing compactin and valuable information during the research. Also, the authors appreciate Ms. Walaiporn Hongrojjanawiwat for the SEM pictures of membranes.

References [1] A. Endo, J. Lipid Res. 33 (1992) 1569. [2] C. Downton, I. Clark, Nature 2 (2003) 343. [3] S&P Index Corporate Profiles, www.sptopix.com, updated on 05/05/02. [4] H. Ishizu, H. Habaki, J. Kawasaki, J. Membr. Sci. 213 (2003) 209. [5] T. Eksangsri, H. Habaki, J. Kawasaki, Chem. Eng. Process. 43 (2004) 1203. [6] T. Eksangsri, H. Habaki, J. Kawasaki, Proc. Regional Symposium on Chem. Eng. 2004, Bangkok, Thailand, session no. JS-057. [7] V.G. Levich, Physicochemical Hydrodynamics, second ed., PrenticeHall, Englewood Cliffs, NJ, 1962, pp. 60–72. [8] R. Bird, W. Stewart, E. Lightfoot, Transport Phenomena, first ed., John Wiley & Sons Inc., New York, 1960, p. 656. [9] R. Basu, K.K. Sirkar, J. Membr. Sci. 75 (1992) 131.