Separation Bfbification

Technology Separation and Purification Technology 12 ( 1997) 99-108 ELSEVIER

Adsorption of 6-aminopenicillanic acid on activated carbon

M. Dutta, R. Baruah, N.N. Dutta * Chemical Engineering Division, Regional Research Laboratory, Jorhat-785 006, India

Received 15 November 1996; accepted 1 April 1997

Abstract

The ads’orption and desorption of 6-aminopenicillanic acid (6-APA) in aqueous solution has been studied using activated carbon as the adsorbent. The extent of adsorption was found to be strongly dependent on the aqueous phase pH and this dependence could be interpreted from a model for neutral species adsorption. Desorptionstudies suggest that a small fraction of 6-APA adsorbs irreversibly on activated carbon. Adsorption equilibrium data were correlated with the Langmuir, Freundlich and Redlich-Peterson expressions with the Langmuir model being found to provide the best fit of the experimental data. The rates of adsorption and desorption appear to follow the first- order kinetics under the experimental conditions used in the study. However, more precise rate expressions requires the inclusion of the external mass transfer effect initially and the particle diffusion effect at the later stage. Adsorption enthalpy calculated from the Van’t Hoff plot was found to be 3.92 kcal mol -l. 0 1997 Elsevier Science B.V.

Keywords: Adsorption; Adsorption enthalpy; Activated carbon; 6-aminopenicillanic acid; Langmuir isotherm; Freundlich isotherm; Redlich-Peterson isotherm

1. Notation KL. k ads

aR parameter of Redlich-Peterson model m b parameter of Redlich-Peterson model c concentration of 6-APA (mol 1-l) N G equilibrium concentration of 6-APA n

(mol 1 - ‘) pk, G concentration of neutral form of 6-APA 4

(mol 1 - ‘) CO initial solute concentration (mol 1-l) qd

G solute concentration at time t (mol 1-l)

4 adsorbent particle diameter (cm) qe K adsorption equilibrium constant k constant in Langmuir equation defined as 40

KG, UK’) R

* Corresponding author.

1383-5866/97/$17.00 0 1997 Elsevier Science B.V. All rights reserved. PZZ S1383-5866(97)00033-6

Langmuir constant (1 mm01 -‘) adsorption rate constant (s-l) mass of adsorbent per litre of particle free slurry (g 1 - ‘) stirring speed (rpm) parameter in Freundlich isotherm model dissociation constant of 6-APA (=pH) amount of 6-APA adsorbed per gram of activated carbon (m mol g-‘) surface concentration at desorption equilib- rium (m mol g- ‘) amount of 6-APA adsorbed at equilibrium (mm01 g - ‘) surface concentration before desorption (mm01 g - ‘) universal gas law constant (kcal g mol-’ K-l)

M. Dutta et al. /Separation and Purification Technology 12 (1997) 99-108 100

ss T t V W

XIII Pl EP PP II/

AC AG"

AH"

AS"

particle surface area (cm-l) absolute temperature (K) time (s) solution volume (1) weight of adsorbent (g) monolayer saturation value (mm01 g-r) mass transfer coefficient (cm s - ‘) porosity of adsorbent particle (-) density of adsorbent particle (g cmw3) term signifying solute activity coefficient (-) change in 6-APA concentration (mol 1 - ‘) standard free energy of adsorption (kcal mol - ‘) standard enthalpy of adsorption (kcal mol - ‘) standard entropy of adsorption (kcal mol - ‘)

2. Introduction

6-APA, a starting material for preparing com- mercially important ampicillin and amoxicillin can be derived from either penicillin V or G via enzy- matic hydrolysis which also produces phenoxya- cetic acid as the side product [ 11. Isolation of 6-APA from the reaction mixture generally involves the use of solvent extraction of the side product with methyl isobutyl ketone at pH 2.5 or adsorption on ion-exchange resin, i.e. Lewatit MP 500A followed by pH adjustment of the aqueous 6-APA solution to pH 7-8, concentration under vacuum and precipitation at the isoelectric point (PI) of pH 4.3. We have been exploring the appli- cation of reactive extraction in liquid membrane and/or adsorption for the recovery of beta-lactam antibiotics from culture broth [2-S]. Though the liquid membrane technique can provide attractive separation selectivity for beta-lactams [9, lo], its commercial exploitation is yet to be established. Adsorption chromatography, recommended for extraction and purification of various hydrophylic products [ 111, can be competitive for various amphoteric beta-latam antibiotics [ lo]. Non-ionic polymeric resins, ion-exchange resins, activated carbon, molecular sieves, etc. have all been pro- posed as candidate adsorbents for isolating hydro-

philic products [ 10,111. A variety of polymeric resins have also been studied for preparative and analytical scale isolation of beta-lactam antibiotics [ 12-171 and plant products, i.e. alkaloids [18]. The early generation of adsorbents was activated carbon, but regeneration problems render its use prohibitive in several cases. However, because of its low cost and easy availability, it has enough prospects for purification of amphoteric cephalo- sporins particularly at low pH condition under which cephalosporins are markedly hydrophobic. Activated carbon has been also used for efficient recovery of cephalexin from the reaction products of enzymatic conversion process [ 191. Though the technology for production of activated carbon with precise and definite pore structure and surface properties has now been well developed, there is very limited or practically no information on sys- tematic studies of adsorption of beta-lactam anti- biotics on activated carbon. In this paper, complementary studies of 6-APA adsorption have been reported with emphasis on adsorption mecha- nism, equilibrium and kinetics.

3. Experimental

6-APA used in this study was obtained from a commercial source (Sigma Chemical Company, St Louis, MO). Buffer reagents such as sodium phos- phate, sodium acetate, sodium carbonate, etc. were supplied by BDH, Bombay, India and were of analytical grade. Granular activated carbon was obtained from E. Merck (India), Bombay. It had a specific surface area of 920 m2 g-’ (by BET N, adsorption), an average diameter of 1.3 x 10m4 m, a porosity of 55%, an apparent density of 410 kg rnw3, a particle density of 1100 kg me3 and sphericity of nearly 1. It was washed with distilled water and dried overnight at around 100°C before use.

Equilibrium isotherms were obtained by con- tacting 100 ml of aqueous 6-APA solution with different amount of activated carbon in a thermo- statted shaker maintained at the desired temper- ature. The initial concentration of 6-APA in the aqueous solution was varied between 8 and 20 mM. The pH of the solution was varied between

M. Dutta et al. j Separation and Purification Technology I2 (1997) 99-108 101

4 and 8 by using buffer agents of appropriate dosages and the contact time was 24 h. After attaining equilibrium, the mixture was allowed to settle and the supernatant liquor was filtered to remove any particulate matter. The clear solution thus obtained was analysed by means of a UV-VIS spectrophotometer (Shimadzu 160A) calibrated at appropriate wavelength depending on the buffer media used for maintaining the pH of the aqueous solution. The amount of 6-APA adsorbed per gram of activated carbon, q (mol g- ‘) was calculated as q= VAC/ W, where, AC is the change in 6-APA concentration (mol l_ ‘), V is the solution volume (l), and W is the weight of adsorbent (g).

Adsorption enthalpy was measured using the method based on the van? Hoff plot. In the van? Hoff method, the temperature dependence of the adsorption equilibrium constant can be related to the adsorption enthalpy via two thermodynamic relationships. The first relationship is:

AG“ = - RTln K= - RTln {$(q/C’,)}, (1)

where, AG“ is the standard free energy of adsorp- tion, R is the gas law constant, T is the temperature in K, and K is the adsorption equilibrium constant. At low solute concentrations, adsorption is limited to the linear region of the isotherm and therefore the equilibrium constant can be related to the adsorption affinity (q/C,). The factor $ includes the terms for the activity coefficient of the solute in the two phases and activity of the unbound adsorption sites. For a narrow range of solute concentrations, II/ may be assumed to be constant under the standard conditions.

The second relationship is:

AG” = AH“ - TAS”, (2)

where AH” and AS” are the standard enthalpy and entropy changes of adsorption, respectively. Combining Eqs. (1) and (2), the following equa- tion is obtained:

ln(q/C,) = - g+[!!&ln*] (3)

Thus, a plot of ln(q/C,) versus l/T should give a straight line with a slope of -AHDIR, from which -AH” can be calculated under the assumption

that AH”, AS” and $ are constant over the temper- ature range of study.

For desorption isotherm studies, solute initial surface concentration, qO was calculated from a mass balance in the loading step and comparing with the value predicted by the adsorption iso- therm. The qO values obtained in equilibrium iso- therm studies were mostly selected for use in the analysis of the desorption equilibrium experiments. Solute surface concentrations, qd, at desorption equilibrium, were determined from a mass balance. Under a set of experimental conditions, both adsorption and desorption isotherms will be com- pared in a single figure.

Experiments on adsorption rates were conducted in a stirred constant volume tank similar to that used in our earlier work [ 8,201. The liquid volume was 150 cm3 with 0.330.35 g of activated carbon samples.

4. Results and discussion

4.1. Adsorption isotherm

6-APA is an amphoteric molecule with pKal, pK,, and isoelectric points (~1) of 2.3, 5.1 and 4.3, respectively. The pH dependence of the adsorption isotherm has been emphatically dis- cussed here as the pH determines the extent of ionization of the molecule, thereby affecting the adsorption affinity. As shown in Fig. 1, the effect of pH on the isotherm is quite apparent and the adsorption increases with a decrease in the pH value. This observation is similar to that obtained for adsorption of cephalosporin-C and other peni- cillins on neutral polymeric sorbents like Amberlite XAD-16, Amberlite XAD-7 (aliphatic esters) [ 12-151, but is in contrast to that for alkaloid adsorption on Amberlite XAD-7 [ 181. The pH dependence can be interpreted by considering the adsorption affinity, expressed as the slope of the linear region of the isotherm (q/C,). As shown in Fig. 2, a strong dependence of q/C, on pH exists. Since the concentration (C,) of the neutral form of 6-APA is related to the pH and the total concentration (C,) by the Henderson-Hasselback

102 M. Dutta et al. / Separation and Purification Technology 12 (1997) 99-108

i-2

t A/-

0

z 0.6

E 3-

0’4

PH 4 5 6 7 a

0.2 . . .:. . .

vycr &--

.

or ’ I I I

0 2 4 G 8 1

C er mmolli

Fig. 1. Adsorption isotherm for 6-APA on activated carbon as a function of pH.

relationship as given by:

c, = G (l+lO*i+pxa)’ (4)

the isotherm, as shown in Fig. 3, follows a model for neutral species adsorption and can represent well the pH variation. This has been demonstrated in the case of the adsorption of penicillin V and cephalosporin-C on a neutral resin [ 131 and in our earlier work for the adsorption of three semisyn- thetic cephalosporins on activated carbon [ 81. The adsorption affinity of 6-APA is relatively lower than those reported in our earlier paper [S] for adsorption of three semisynthetic cephalosporins, i.e. cephalexin, 7-aminocephalosporanic acid and cefadroxyl, on activated carbon. The adsorption capacity of various penicillins and cephalosporins on non-ionic macroporous resins was found to decrease with increase of pH and this dependence was quantitatively described by model incorporat- ing hydronium ion concentration and dissociation constant [ 151. The pH versus q/C, profile obtained

Fig. 2. The affinity of 6-APA adsorption on activated carbon as a function of pH.

in this work perhaps indicates that the neutral form of the antibiotics should be adsorbed and this adsorption may be attributed to the hydro- phobic interaction. The adsorption affinity of the p-lactam studied here and in our previous paper [8] increases in the order cephalexinb cefadroxil > 7-ACA > 6-APA. Thus, considering their structures, it appears that a relationship exists between hydrophobicity and adsorption affinity and the adsorption may be attributed to hydro- phobic interaction. In general, for the adsorption of solutes from aqueous solutions onto solid sur- faces which do not strongly interact with the solute, hydrophobic interaction is the major driv- ing force for adsorption [21].

The adsorption equilibrium was interpreted from Langmuir, Freundlich and Redlich-Peterson isotherm. Table 1 shows the estimated parameter values for all the isotherms. It appears that

M. Dutta et al. / Separation and Purijication Technology 12 (1997) 99-108 103

, .4, O-,004 0;006 0;OlZ 0*?16 @,02 O/op?1

1’2 .

1'0

0-l 0’8

a E E 0’61 .

V I

Fig. 3. Dependence of adsorption on the concentration of the neutral form of 6-APA.

Langmuir isotherm provides the most satisfactory representation of the experimental data almost at all pH values studied. The Langmuir model was found to be applicable for adsorption of cephalosporin-C and streptomycin on ion- exchange resin over a range of practically relevant liquid-phase concentrations, [ 13,251. The adsorp- tion of 7-ACA, cephalexin and cefadroxil on acti- vated carbon could be well described by both

Table 1 Parameter values for adsorption isotherm of 6-APA at 25°C

Langmuir and Freundlich models in our earlier work [8].

4.2. Adsorption enthalpy

The effect of temperature on the isotherm was evaluated by measuring the adsorption at 25 and 45°C and at a constant pH of 6. As shown in Fig. 4, the adsorption intensity increases with tem-

0.1 L //

00 0 I 2 3 4 5 6 7 8 910

C e,mmol/g

Fig. 4. Effect of temperature on adsorption isotherm of 6-APA. (pH=6.0).

PH Langmuir q = KX,C,/( 1+ KC,) Freundlich q = K&’ Redlich-Peterson q = KC,/( 1 + a,c)

K &I RMS (%) KF n RMS (%) K oR b RMS (%)

4 1.90843 1.480485 6.7593 0.45780 1.80743 9.7398 1.90801 3.0802 0.5584 8.25793 5 2.69970 1.027012 4.6819 0.28273 1.78845 8.2754 2.69970 8.3488 0.4963 8.25394 6 5.6798 2.826968 2.7649 0.17965 1.22000 2.05026 15.67980 86.469 0.1809 2.00299 7 1.70061 0.241573 2.0611 0.11353 3.62940 2.64966 1.70061 14.208 0.7435 2.60364 8 1.58818 0.235894 2.5941 0.10492 3.07128 3.24089 1.58818 14.399 0.6897 3.06771

RMS=lkdw(%)

N,, = number of points in a fitted experimental curve.

104 M. Dutta et al. 1 Separation and Purification Technology 12 (1997) 99-108

perature and the extent of increase being more pronounced at high equilibrium solute concen- tration exhibiting around a 20% increase in adsorp- tion capacity ‘near the equilibrium saturation. From a Vant’ Hoff plot (Fig. 5), the estimated adsorption enthalpy value AH”, is - 3.92 kcal mol -l. The order of magnitude of this AH” value is in good agreement with the calorimet- rically measured values reported for adsorption of cephalosporin-C onto polymeric adsorbent [ 131.

4.3. Desorption isotherm

The desorption equilibrium data were generated at two pH values and over a range of initial solute surface concentrations. A comparison of the adsorption and desorption equilibrium isotherms are shown in Fig. 6. It is apparent that the desorp- tion isotherm points lie marginally above the adsorption isotherms. Since, for a fully reversible adsorption, the isotherm data should be statistic- ally indistinguishable, the observed hysteresis between adsorption and desorption in Fig. 6 sug- gest that a small fraction of solute is irreversibly adsorbed at both the pH studied in this work. The amount of reversible 6-APA adsorption was calcu-

3 3.1 3-2 3’3 3.4

l/T x lo3

Fig. 5. Typical van’t Hoff plot for adsorption of 6-APA on activated carbon.

0.4; ! ” / / Symbol pH

@,O 6

o,a 4

"0 2 4 6 a ~ C e, mmol lg

Fig. 6. Comparison of the adsorption and desorption isotherms for the 6-APA-activated carbon system. Open and crossed sym- bols for desorption and adsorption, respectively.

lated from a mass balance method described pre- viously for adsorption-desorption of toluene in an aqueous phase on activated carbon [ 221; the results are shown in Fig. 7 in terms of the fraction of reversible 6-APA adsorption versus initial surface

0’5L I , 0 0.2 0.4 0.6 0.8 1.0 1.2 1.4

Initial 6 APA surface concentralion ( m mol 19:)

Fig. 7. Fraction of reversible adsorption on activated carbon as a function of the initial 6-APA surface concentration (pH= 4.0).

M. Dutta et al. /Separation and Purijication Technology 12 (1997) 99-108 105

concentration for the case of adsorption-desorp- tion at pH 4.0. The results indicate that over the entire range of surface concentrations studied, the fraction of reversible toluene adsorption remains essentially in the range 0.93-0.95. In general, the fraction of irreversible adsorption is expected to be high at a low surface concentration owing to high active sites available and a high energy of activation. However, our results did not exhibit this and such anamoly may be merely attributed to the small fraction of irreversible adsorption observed and the effect may be even masked by small experimental errors. Such a behaviour has been reported for the aqueous toluene-activated carbon adsorption system [22].

4.4. Adsorption rate studies

The adsorption rate curve is shown in Fig. 8, which pertains to a constant liquid phase stirring speed of 800 rpm and a constant initial 6-APA concentration of 20 mM. The rate curve exhibits a rapid initial uptake followed by a relatively slow approach to equilibrium similar to that observed for three semisynthetic cephalosporins as reported in our earlier paper [8] for identical activated carbon particles. This behaviour may not be con-

lh 1.4

i2 rb 1 1.2

-lO-

? _

. 1.0

-0.6 ,"

- z E

-056 _g

c

.0.4

2 4 6 8 10 12 lb 0

Time (Hr )

Fig. 8. Adsorption rate curve for 6-APA adsorption on acti- vated carbon. (pH=6, W=O.35 g, N=SOO rpm).

sistent with a single effective parameter model. Because of the rough external surface of the acti- vated carbon, external mass transfer can be sig- nificant even under vigorous stirring of the liquid phase and should not be ignored in modelling adsorption kinetics of organic from an aqueous solution [22]. The adsorption kinetics was exam- ined with a first-order rate expression, the so-called Lagergren equation [23]‘:

log(q, -q) = log qe -

where qe and q are the amounts of 6-APA adsorbed (m mol g-‘) at equilibrium and any time (t), respectively, and kads (s- ‘) is the adsorption rate constant. Fig. 9 shows reasonably good linear- ity on the plot of log(q,-q) versus t, indicating that the adsorption rate can be well described by first-order kinetics before attaining equilibrium. The value of the adsorption rate constant was

-o’llv -0.1 K\ i

-0.5

I

--0'5

2 1 : - -1.0 :

I

2 :

u

_c

. -1.5

t 1

-2.0 0 2 4 6 6 10 12 1L

Time (Hr)

Fig. 9. Lagergren and McKay plot for the adsorption of 6-APA on activated carbon. Conditions are the same as in Fig. 7.

‘Ref. [23] cites Lagergen (1972) Bil. K. Svenska Ventenskapasakad Handl. 24, 1898.

106 M. Dutta et al. / Separation and Purijication Technology 12 (1997) 99-108

found to be 5.59 x 10-5s-‘, indicating a rather slow adsorption rate.

The external mass transfer effect on the adsorp- tion kinetics can be analysed by using the McKay [ 241 equation valid for negligible intraparticle diffusion resistance and for linear isotherm:

(6)

where C, and C, are the solute concentration initially and at any time (t), respectively, m (g 1 - ‘) is the mass of adsorbent per litre of particle free slurry, k is the constant in the Langmuir equation defined as Krx, (1 g- ‘) where KL is the Langmuir constant (1 mm01 -‘) and X, is the monolayer saturation value (mm01 g-l), pi (cm s-l) and S, (cm-‘) are the mass transfer coefficients and particle surface area, respectively.

S, is given by:

6W s, =

Q,( 1 -cp) (7)

where W is the weight, dP is the diameter, pp is the density and ep is the porosity (subscript p refers to particles). The McKay plot is shown in Fig. 9 in terms of ln[C,/C, - l/( 1 + mk)] versus t. It is appar- ent from the linearity of the plot that external mass transfer plays predominant role in the adsorption process. The mass transfer coefficient, /I1 calculated from the slope and intercept of the plot was found to be 9.917 x 10F5 ems-‘. However, deviation of the plot at the initial stage of adsorption infers a different rate controlling step.

The role of the intraparticle diffusion on the adsorption kinetics was examined from a graphical relationship between q and square root of the time as shown in Fig. 10. The linearity of the plot indicates the effect of intraparticle diffusion on the adsorption process. However, as the plot does not appear to pass through the origin, the pore diffu- sion alone may not be the rate controlling step.

4.5. Desorption rate studies

From the results of the desorption equilibrium studies, it may be inferred that more than 93% of

.; 1’0 -

i E

Y u -

o-5 -

1

/

0

/

/”

0 1 2 3 to.5 ( +jr0’5 )

Fig. 10. Intraparticle diffusion plot for the adsorption of 6-APA on activated carbon. Conditions are the same as in Fig. 7.

the total 6-APA originally adsorbed contributes to the observed desorption equilibrium. The desorp- tion rate shown in Fig. 11 represents an equilibra- tion time nearly identical to that of adsorption

0 ? 4 6 s 10 1: 1: 16

Time (Hr )

Fig. 11. Rate curve for 6-APA desorption from activated carbon. (pH = 6.0, R= 0.35 g, N = 800 rpm, initial surface con- centration is 1.21 m mol g-l).

M. Dutta et al. /Separation and PuriJication Technology 12 (1997) 99-108 107

equilibration time. The initial 6-APA surface con- centration was determined from the adsorption isotherm. The equilibrium value of bulk solute concentration represents around 94% of the total initial surface concentration and was therefore available for desorption. It is therefore logical to assume fast intrinsic desorption kinetics for the reversibly adsorbed 6-APA. However, it is neces- sary to make systematic investigation at different particle sizes and loading followed by accurate model analysis to provide a better description of the desorption kinetics.

5. Conclusion

The adsorption of 6-APA from aqueous solution on activated carbon depends strongly on the pH of the media. The adsorption affinity decreases with increase of pH which infers applicability of the model for neutral species adsorption. The adsorption equilibrium may be well represented by the Langmuir isotherm. Increase of temperature increases the adsorption suggesting an endothermic process, the value of adsorption enthalpy being 3.92 kcal mol -l. The adsorption process is highly reversible, the extent of reversibly adsorbed 6-APA being around 93%. The rate of adsorption appears to be controlled by both external film diffusion and particle surface diffusion. A more detailed model analysis is however necessary to provide a better description of the adsorption-desorption kinetics.

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