Solubility of Cefpiramide Sodium in Binary Ethanol + Water and 2

Article pubs.acs.org/jced

Solubility of Cefpiramide Sodium in Binary Ethanol + Water and 2‑Propanol + Water Solvent Mixtures Fengxiang Tang,* Shan Wu, Fuqiang Wu, and Suying Zhao* College of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou 350108, Fujian, China ABSTRACT: The solubility of cefpiramide sodium in binary solvent mixtures of ethanol + water and 2-propanol + water was determined by a steady-state method from (278.2 to 303.2) K and in the initial mole fraction range of alcohol (ethanol or 2-propanol) in the solvent mixture at about 0.4 to 0.8. Cefpiramide sodium exhibits the same order of magnitude of solubility in both binary systems. The solubility decreases with the increase of the initial mole fraction of alcohol and increases with increasing temperature. Dilution crystallization or dilution crystallization incorporated with cooling crystallization will be more suitable than pure cooling crystallization for the purification of cefpiramide sodium. The Jouyban−Acree model, combined with the van’t Hoff equation, was used to correlate the solubility data. The combined model was further simplified so that each item in the model is statistically significant at the 5 % level. The simplified combined model gives a mean relative deviation of 5.3 % for the ethanol + water system, and 3.0 % for the 2propanol + water system. This model demonstrates good fitting with the experimental solubility data, and could be used for related process design in the pharmaceutical industry.

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INTRODUCTION Cefpiramide sodium (CAS Registry No. 74849-93-7, see Figure 1 for its chemical structure) is classified as a semisynthetic

propanol) about from 0.4 to 0.8. The experimental solubility data was correlated by a combined model. We hope that the solubility model presented in this work will be useful for the reactor design and optimization of the purification of cefpiramide sodium.

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EXPERIMENTAL SECTION Materials. A detailed description of the chemicals used in this paper is given in Table 1. Double distilled water with a Table 1. Description of Materials Used in This Paper chemical name

Figure 1. Chemical structure of cefpiramide sodium.

cefpiramide sodium ethanol 2-propanol water

third-generation cephalosporin. It displays a broad spectrum of antibacterial activity against gram-positive, gram-negative, and anaerobic bacteria. Compared with other cephalosporins, it is especially effective against Pseudomonas aeruginosa. It works by inhibiting bacterial cell wall biosynthesis.1,2 Crystallization is a key procedure in the purification of cefpiramide sodium and hence its solubility data are especially important. The Japanese Pharmacopoeia says that cefpiramide sodium is very soluble in dimethylsulfoxide, freely soluble in water, sparingly soluble in methanol, and slightly soluble in ethanol.3 However, no quantitative solubility data in these or other solvents has been reported according to a bibliographical search. In this paper, the solubility of cefpiramide sodium in binary ethanol + water and 2-propanol + water solvent mixtures was determined using a steady-state method from (273.2 to 303.2) K and in the initial mole fraction range of alcohol (ethanol or 2© 2013 American Chemical Society

source Hubei Xin Runde Chemical Industry Co. Ltd., China Sinopharm Chemical Reagent Co., China Sinopharm Chemical Reagent Co., China lab made

initial mass fraction purity 0.950 0.995 0.995 double distilled

conductivity ranging from (1.2 to 1.4) μS·cm−1 was used in all experiments. Cefpiramide sodium with a mass fraction of 0.995 (determined by high-performance liquid chromatography3) was prepared from the crude cefpiramide sodium shown in Table 1 by recrystallization from the solvent mixture of acetone and water (9:1, v/v) three times. The recrystallized cefpiramide sodium was amorphous. Received: September 7, 2013 Accepted: November 18, 2013 Published: November 22, 2013 56

dx.doi.org/10.1021/je400786n | J. Chem. Eng. Data 2014, 59, 56−60

Journal of Chemical & Engineering Data

Article

Apparatus and Procedures. The experimental setup for the solubility measurement is similar to that described previously.4 In a 100 mL jacket glass vessel with circulating water from a super-thermostatted water bath (501A, Shanghai Jinghong Laboratory Instrument Co., Ltd., uncertainty: ± 0.1 °C), excess solid cefpiramide sodium was put into 50 mL of binary solvent mixtures, which were prepared by mixing a certain quantity of two solvents (ethanol or 2-propanol and water) measured by an analytical balance (ACCULAB-Sartorius ALC-110.4, Germany) with an uncertainty of ± 0.0001 g. A mercury-glass thermometer with an uncertainty of ± 0.1 °C was used to measure the temperature of the solution. A condenser was assembled to prevent the evaporation of the solvent. After being stirred for 4 h to reach equilibrium at a desired temperature, the solution was allowed to stand for 2 h, and then 0.5 mL of supernatant solution was taken, filtered through a 0.45 μm micro-membrane, and then appropriately diluted with water for spectrophometric analysis. The absorbance was determined on a Shimadzu UV-1800 spectrophotometer at 272 nm. A calibration graph with the concentration of cefpiramide sodium ranging from (7.88·10−6 to 5.52·10−5) mol·L−1 and corresponding molar absorption coefficient (ε) ranging from (12946.2 to 14088.6) L·mol−1·cm−1 was used. All of the measurements are repeated four times, and the average of the four measurements is considered to be the solubility. The mole fraction solubility ((xA)m,T) of the solute in the binary solvent mixture at temperature T and the initial mole fraction (x0B) of alcohol (ethanol or 2-propanol) in the binary solvent mixture were calculated on the basis of eq 1 and eq 2, respectively, (xA )m,T = x B0 =

mA /MA mA /MA + mB /MB + mC/MC

mB /MB mB /MB + mC /MC

Table 2. Mole Fraction Solubility ((xA)m,T) of Cefpiramide Sodium in Binary Ethanol (B) + Water (C) Solvent Mixtures at P = 0.1 MPaa x0B 0.4048 0.5003 0.5972 0.6969 0.8062 0.4048 0.5003 0.5972 0.6969 0.8062 0.4048 0.5003 0.5972 0.6969 0.8062

(xA)m,Texp

(xA)m,Tcal (eq 9)

T = 278.2 K 0.003660 0.003904 0.001900 0.001695 0.000795 0.000737 0.000420 0.000366 0.000260 0.000277 T = 283.2 K 0.004420 0.004718 0.002110 0.002005 0.000854 0.000853 0.000440 0.000413 0.000284 0.000301 T = 288.2 K 0.005400 0.005666 0.002370 0.002358 0.000929 0.000982 0.000464 0.000463 0.000312 0.000326

x0B 0.4048 0.5003 0.5972 0.6969 0.8062 0.4048 0.5003 0.5972 0.6969 0.8062 0.4048 0.5003 0.5972 0.6969 0.8062

(xA)m,Texp

(xA)m,Tcal (eq 9)

T = 293.2 K 0.006600 0.006761 0.002710 0.002758 0.001040 0.001125 0.000505 0.000518 0.000348 0.000353 T = 298.2 K 0.008360 0.008021 0.003200 0.003208 0.001190 0.001283 0.000563 0.000578 0.000398 0.00038 T = 303.2 K 0.010820 0.009461 0.003840 0.003714 0.001350 0.001457 0.000631 0.000642 0.000476 0.000409

a 0 xB

is the initial mole fraction of ethanol in the binary solvent mixture; (xA)m,Texp is the experimentally determined solubility; (xA)m,Tcal (eq 9) is the calculated solubility according to eq 9. The standard uncertainty u is u(T) = 0.1 K; relative standard uncertainty u is ur((xA)m,T) = 0.03.

Table 3. Mole Fraction Solubility ((xA)m,T) of Cefpiramide Sodium in Binary 2-Propanol (B) + Water (C) Solvent Mixtures at P = 0.1 MPaa

(1)

x0B 0.3995 0.5068 0.6043 0.7022 0.7999

(2)

where mA, mB, and mC denote the mass of cefpiramide sodium, solvent B ((ethanol or 2-propanol)) and solvent C (water) used in the experiment, and MA, MB, and MC are the respective molecular weights.

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0.3995 0.5068 0.6043 0.7022 0.7999

RESULTS AND DISCUSSION Solubility Data. Our experimental observation told us that cefpiramide sodium tended to be unstable when the temperature exceeded 308.2 K, and hence the experimental temperature was selected in the range from (278.2 to 303.2) K. In addition, the mixture composed of excess cefpiramide sodium in pure ethanol or 2-propanol was observed to become pastelike under continuous stirring, and the mixture composed of excess cefpiramide sodium in pure water or in the alcohol (ethanol or 2-propanol) + water solvent mixture which contained a small amount of alcohol was observed to become jellylike. Thus, it is difficult to determine the solubility of cefpiramide sodium in pure ethanol, 2-propanol, or water, and that in the binary mixture with low initial alcohol mole fraction using the method mentioned above. The initial alcohol mole fraction range was thus kept approximately from 0.4 to 0.8. The experimental solubility data of cefpiramide sodium in the binary solvent mixtures of ethanol + water and 2-propanol + water are shown in Tables 2 and 3, and Figure 2. As shown in Tables 2 and 3, cefpiramide sodium gives the same order of magnitude of solubility in both of the binary systems. In the

0.3995 0.5068 0.6043 0.7022 0.7999

(xA)m,Texp

(xA)m,Tcal (eq 9)

T = 278.2 K 0.002540 0.002652 0.000806 0.000761 0.000284 0.000266 0.000096 0.000092 0.000032 0.000031 T = 283.2 K 0.003360 0.003490 0.000955 0.000945 0.000321 0.000313 0.000101 0.000102 0.000033 0.000033 T = 288.2 K 0.004460 0.004550 0.001130 0.001165 0.000361 0.000366 0.000109 0.000114 0.000034 0.000034

x0B 0.3995 0.5068 0.6043 0.7022 0.7999 0.3995 0.5068 0.6043 0.7022 0.7999 0.3995 0.5068 0.6043 0.7022 0.7999

(xA)m,Texp

(xA)m,Tcal (eq 9)

T = 293.2 K 0.005920 0.005878 0.001360 0.001425 0.000408 0.000425 0.000119 0.000126 0.000036 0.000036 T = 298.2 K 0.007820 0.007528 0.001670 0.001731 0.000483 0.000492 0.000132 0.000138 0.000038 0.000038 T = 303.2 K 0.01021 0.009564 0.002040 0.002090 0.000567 0.000566 0.000147 0.000152 0.000042 0.000040

a 0 xB

is the initial mole fraction of 2-propanol in the binary solvent mixture; (xA)m,Texp is the experimentally determined solubility; (xA)m,Tcal (eq 9) is the calculated solubility according to eq 9. The standard uncertainty u is u(T) = 0.1 K; relative standard uncertainty u is ur((xA)m,T) = 0.03.

two solvent mixtures, the solubility of cefpiramide sodium increases with increasing temperature, whereas it decreases with the increase of the initial mole fraction of alcohol in the solvent mixture. Since ethanol is less polar than water, it is expected that the solubility of cefpiramide sodium decreases with the 57



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Figure 2. Solubility of cefpiramide sodium at various temperatures and compositions in (a) ethanol + water and (b) 2-propanol + water binary mixtures: ■, experimental data points; solid line, calculated from eq 9.

popular due to its ability of estimating the solute solubility with respect to both temperature and solvent composition of binary solvent mixtures in a fairly simple way, as described in eq 3.

increase of alcohol content. For all the temperatures given in Figure 2, the solubility of cefpiramide sodium first decreases remarkably in the initial mole fraction range of alcohol from 0.4 to 0.6, and then drops gradually in the corresponding range about from 0.6 to 0.8. Among the five given temperatures ((278.2, 283.2, 288.2, 293.2, 298.2, and 303.2) K), the highest reduction amplitude of solubility takes place at 303.2 K as the initial alcohol mole fraction increases about from 0.4 to 0.8. On the other hand, temperature shows an obvious effect on the solubility when the initial mole fraction is about from 0.4 to 0.5, and less effect is observed as the initial alcohol mole fraction is higher than 0.5. Although there is a significant decline in solubility occurring at the initial alcohol mole fraction of 0.4 when the temperature drops from 303.2 K to 278.2 K, this decline is much smaller than the highest reduction amplitude of solubility mentioned above. Therefore, dilution crystallization will be more suitable than cooling crystallization for the purification of cefpiramide sodium. However, an ideal purification process should consist of both of the two kinds of crystallization. A typical purification process may comprise dissolving cefpiramide sodium in a binary alcohol (ethanol or 2propanol) + water solvent mixture of low initial mole fraction of alcohol (for example, 0.4 or less) at a high temperature (for example, 303.2 K), then adding alcohol (ethanol or 2-propanol) into this mixture until the solvent alcohol composition reaches a higher value (for example, 0.8) and further cooling the mixture to a lower temperature (for example, 278.2 K, or even lower), or vice versa. In this sense, these solubility data can be used as fundamentals for the purification process of cefpiramide sodium. Data Correlation. The mathematical models extensively used for describing the solubility data of binary solvent mixtures mainly include two classes: activity-coefficient-related models based on solid−liquid equilibrium5 and semiempirical equations. The first class of models depends on a known fusion temperature of solute. Cefpiramide sodium decomposes easily at high temperatures, and it is difficult to obtain its fusion temperature. The second class of models covers temperaturedependent equations such as the modified Apelblat equation,6 and the van’t Hoff equation,7 solvent-composition-dependent equations such as the combined nearly ideal binary solvent/ Redlich−Kister (CNIBS/R-K) model proposed by Acree and his co-workers,8−10 and the equations which is both temperature-dependent and solvent-composition-dependent, such as the Jouyban−Acree model.11−14 Among these various semiempirical equations, the Jouyban−Acree model is particularly

ln(xA )m,T = x B0 ln(xA )B,T + xC0 ln(xA )C,T n

+ x B0xC0 ∑ i=0

x0B

Ji T

(x B0 − xC0)i

(3)

x0C

where and refer to the initial mole fraction of solvent B and C in the binary solvent mixture and x0C = 1 − x0B; (xA)i,T is the mole fraction solubility of the solute in monosolvent i (i = B, C); Ji terms are the model parameters; n can range from 0 to 3 (usually, n = 2). Obviously, the Jouyban−Acree model depends on the solute solubilities in monsolvents, and becomes useless when the solute solubilities in monsolvents are not available. However, if the solute solubility ((xA)i,T) in monosolvent i (i = B, C) in the Jouyban−Acree model is expressed by the van’t Hoff equation as follows15 ln(xA )B,T = a1 +

b1 T

(4)

ln(xA )C,T = a 2 +

b2 T

(5)

where a1, b1, a2, and b2 are the model parameters. The substitution of eqs 4 and 5 into eq 3 followed by rearrangement yield eq 6. ln(xA )m,T = a 2 +

b2 + (a1 − a 2)x B0 T

+ (b1 − b2 + j0 − j1 + j2 ) + (3J1 − J0 − 5J2 ) − 4J2

x B0 T

(x B0) (x 0)3 + (8J2 − 2J1) B T T

(x B0)4 T

(6)

Equation 6 can be simplified as x0 (x 0)2 A2 + A3x B0 + A4 B + A5 B T T T 0 3 0 4 (x ) (x ) + A6 B + A 7 B T T

ln(xA)m,T = A1 +

58

(7)



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Table 4. Parameters and P-Values of eqs 7 and 9 for Cefpiramide Sodium in Binary Solvents Mixtures ethanol + water eq 7

2-propanol + water eq 9

parameters

parameter value

P-value

A1 A2 A3 A4 A5 A6 A7 r 100MRD

14.03 −1.040·104 −21.74 4.423·104 −1.005·105 1.060·105 −3.974·104 0.997 5.1

0.0000 0.0083 0.0000 0.0914 0.1349 0.1601 0.2018

eq 7 P-value

parameter value

P-value

13.91 −4099 −21.54

0.0000 0.0000 0.0000

1.365·104 −2.233·104 1.328·104 0.997 5.3

0.0004 0.0006 0.0004

26.57 −5137 −42.43 −9124 4.344·104 −4.600·104 1.795·104 0.999 3.3

0.0000 0.0869 0.0000 0.6542 0.4138 0.4434 0.4716

parameter value

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N

((xA )m,Texp )i − ((xA )m,Tcal )i )

MRD =

((xA )m,Texp )i

N

(8)

where N, ((xA)m,Texp)i and ((xA)m,Tcal)i are the number of experimental data points, the experimental solubility, and the solubility calculated from eq 7 or eq 9. As can be seen in Table 4, eq 7 provides a MRD value of 5.1 % and 3.3 % for the ethanol + water system and the 2-propanol + water system, respectively. The corresponding correlation coefficient is 0.997 and 0.999. In terms of the MRD values and the correlation coefficients, eq 7 can present a good mathematical representation of the experimental solubility of cefpiramide sodium in the binary solvent mixtures of ethanol + water, and 2-propanol + water. However, not every associated P-value (Table 4), which indicates the statistical significance level of each item in the right side of eq 7, is less than the significance level α, which is often 0.05.16,17 Namely, not every item in the right side of eq 7 is statistically significant. After the fourth term on the right side of eq 7 was removed, eq 7 was simplified into eq 9. The model parameters in eq 9 was re-estimated with the linear least-squares method and all the associated P-values were found to be less than 0.05 as shown in Table 4. This shows that all six items in the right side of eq 9 are statistically significant. (x 0)2 (x 0)3 A2 + A3x B0 + A5 B + A 6 B T T T (x B0)4 + A7 T

parameter value

P-value

26.59 −6430 −42.47

0.0000 0.0000 0.0000

1.979·104 −1.931·104 6876 0.999 3.0

0.0000 0.0001 0.0090

CONCLUSIONS The solubility of cefpiramide sodium in the binary ethanol + water and 2-propanol + water solvent mixtures increases with increasing temperature, and a relatively remarkable increase with the temperature occurs when the initial mole fraction of alcohol (ethanol or 2-propanol) in the solvent mixture is kept in a lower range (about from 0.4 to 0.5). The solubility of cefpiramide sodium decreases with an increase of the initial mole fraction of alcohol and particularly drops rapidly in a lower mole fraction range of alcohol (about from 0.4 to 0.6). The solubility of cefpiramide sodium in the two binary systems shares the same magnitude. According to the change trend of the solubility of cefpiramide sodium with temperature and alcohol content, dilution crystallization or dilution crystallization integrated with cooling crystallization will be a better choice for the purification of cefpiramide sodium. The calculated solubilities of cefpiramide sodium based on the simplified combined model derived from the van’t Hoff and Jouyban−Acree equations show good agreement with the experimental values. This proves that the simplified combined model can be employed for the reactor or process design of cefpiramide sodium purification.

where A1, A2, ...., A7 are the model parameters. Equation 7 represents the combined model between the van’t Hoff equation and the Jouyban−Acree model. The model parameter values of eq 7 were directly obtained by the linear least-squares method from the experimental data, and are shown in Table 4, together with corresponding P-values, correlation coefficients (r), and mean relative deviations (MRD). MRD is defined as ∑i = 1

eq 9

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]; [email protected]. Fax: 860591-22866227. Notes

The authors declare no competing financial interest.

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REFERENCES

(1) Yan, X. N.; Liu, B. S.; Chong, B. H.; Cao, S. Interaction of cefpiramide sodium with bovine hemoglobin and effect of the coexistent metal ion on the protein-drug association. J. Lumin. 2013, 142, 155−162. (2) Hu, L. F.; Liu, L. Cefpiramide sodium hydrate, preparation method and uses thereof. WO 2011/144021 A1, Nov 24, 2011. (3) Japanese Minister of Health, Labour and Welfare. The Japanese Pharmacopoeia, 16th ed.; Hirokawa Publishing Co.: Tokyo, 2011. (4) Tang, F. X.; Guo, Z. L.; Li, D. Q.; Chen, H. Y; Zhao, S. Y. Dissociation constant and solubility of (S)-2-hydroxy-4-phenylbutyric Acid. J. Chem. Eng. Data 2013, 58, 1265−1270. (5) Prausnitz, J. M. Molecular Thermodynamics of Fluid-Phase Equilibria, 2nd ed.; Prentice-Hall: Englewood Cliffs, NJ, 1985. (6) Apelblat, A.; Manzurola, E. Solubilities of o-acetylsalicylic, 4aminosalicylic, 3,5-dinitrosalicylic, and p-toluic acid and magnesiumDL-aspartate in water from T = 278 to 348 K. Chem. Thermodyn. 1999, 31, 85−91.

ln(xA )m,T = A1 +

(9)

Equation 9 almost retains the similar MRD values and correlation coefficients as eq 7 for the two binary systems. This suggests that eq 9 fits well with the experimental solubility data. Figure 2 also elucidates that the calculated solubility based on the simplified combined model (eq 9) agrees well with the experimentally determined solubility. 59



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(7) Grant, D. J. W.; Mehdizadeh, M.; Chow, A. H. L.; Fairbrother, J. E. Non-linear van’ t Hoff solubility-temperature plots and their pharmaceutical interpretation. Int. J. Pharm. 1984, 18, 25−38. (8) Acree, W. E., Jr.; McCargar, J. W.; Zvaigzne, A. L.; Teng, L. L. Mathematical representation of thermodynamic properties. Carbazole solubilities in binary alkane + dibutyl ether and alkane + tetrahydropyran solvent mixture. Phys. Chem. Liq. 1991, 23, 27−35. (9) Acree, W. E., Jr.; Zvaigzne, A. L. Thermodynamic properties of nonelectrolyte solutions. Part 4. Estimation and mathematical representation of solute activity coefficients and solubilities in binary solvents using the NIBS and modified Wilson equation. Thermochim. Acta 1991, 178, 151−167. (10) Acree, W. E., Jr. Mathematical representation of thermodynamic properties. Part 2. Derivation of the combined nearly ideal binary solvent (NIBS)/Redlich−Kister mathematical representation from a two-body and three-body interactional mixing model. Thermochim. Acta 1992, 198, 71−79. (11) Jouyban-Gharamaleki, A.; Acree, W. E., Jr. Comparison of models for describing multiple peaks in solubility profiles. Int. J. Pharm. 1998, 167, 177−182. (12) Jouyban-Gharamaleki, A.; Acree, W. E., Jr. In silico prediction of drug solubility in water−ethanol mixtures using Jouyban−Acree Model. J. Pharm. Pharm. Sci. 2006, 9, 262−269. (13) Jouyban, A. Review of the cosolvency models for predicting solubility of drugs in water−cosolvent mixtures. J. Pharm. Pharmaceut. Sci. 2008, 11, 32−58. (14) Fakhree, M. A. A.; Ahmadian, S.; Panahi-Azar, V.; Acree, W. E., Jr.; Jouyban, A. Solubility of 2-hydroxybenzoic acid in water, 1propanol, 2-propanol, and 2-propanone at (298.2 to 338.2) K and their aqueous binary mixtures at 298.2 K. J. Chem. Eng. Data 2012, 57, 3303−3307. (15) Sardari, F.; Jouyban, A. Solubility of 3-ethyl-5-methyl-(4RS)-2((2-aminoethoxy)methyl)-4-(2-chlorophenyl)-1,4-dihydro-6-methyl3,5-pyridinedicarboxylate monobenzenesulfonate (Amlodipine Besylate) in ethanol + water and propane-1,2-diol + water mixtures at various temperatures. J. Chem. Eng. Data 2012, 57, 2848−2854. (16) Ranjan, D.; Hasan, S. H. Parametric optimization of selenite and selenate biosorption using wheat bran in batch and continuous mode. J. Chem. Eng. Data 2010, 55, 4808−4816. (17) Torné-Fernández, V.; Mateo-Sanz, J. M.; Montané, D.; Fierro, V. Statistical optimization of the synthesis of highly microporous carbons by chemical activation of Kraft lignin with NaOH. J. Chem. Eng. Data 2009, 54, 2216−2221.

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Solubility of Cefpiramide Sodium in Binary Ethanol + Water and 2

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