• KSBB Journal
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• v.17 no.6
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• pp.543-548
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• 2002

The enantioselective esterification of racemic ibuprofen catalyzed by a Candida rugosa lipase was studied according to reaction conditions such as a lipase concentration, reaction temperature, alcohol chain length and alcohol concentration. The S-(+)-ibuprofen alkyl esters prepared were converted to S-(+)-ibuprofen by hydrolysis with sulfuric acid as a catalyst. High conversions in the esterifications were obtained at 60$^{\circ}C$ and an equimolar ratio of octanol to ibuprofen. The initial reaction rate of the esterification decreased with increasing octanol concentration. Conversion and initial reaction rate increased with increasing alcohol chain length. Values of enantiomeric excess(ee) according to esterification reaction conditions did not change below 60$^{\circ}C$. On the other hand, values of conversion and ee for the chemical hydrolysis of S-(+)-ibuprofen alkyl esters were independent of alcohol alkyl chain length. Optical resolution of racemic ibuprofen was achieved by lipase catalyzed esterification and chemical hydrolysis. The separation method provided a high yield and enantioselectivity for the production of S-(+)-ibuprofen from racemic ibuprofen.

• Korean Chemical Engineering Research
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• v.47 no.1
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• pp.54-58
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• 2009

Ketoprofen and ibuprofen are non-steroid anti-inflammatory drug(NSAID) that have analgesic and antipyretic properties. (S)-ketoprofen and (S)-ibuprofen have pharmacological activity, while (R)-ketoprofen and (R)-ibuprofen are either inactive or have side effect. The chiral separation of racemic ketoprofen and ibuprofen enantiomers was carried out by using a Kromasil HPLC column. Some chromatographic parameters (selectivity, resolution, number of theoretical plates and ${\Delta}H$) are calculated under different mobile phase compositions of hexane/t-BME/acetic acid and temperatures. The selectivity, resolution and number of theoretical plates were observed high at $25^{\circ}C$ and the composition of hexane/t-BME/acetic acid (80/20/0.1).

• KSBB Journal
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• v.19 no.4
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• pp.263-268
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• 2004

The separation method using chiral stationary phase in preparation of chiral compound was wildly used, but in this work, supercritical fluid chromatography was suggested in the stability to resolve the chiral mixtures. To determine the optimum operating condition of the racemic ibuprofen, the retention factor and resolution with change in pressures, temperatures and the contents of IPA % (vol.) in CO$_2$ were investigated. The retention factor was decreased with increase in pressure and decrease in temperature. The factor was also influenced by the content of IPA in mobile phase, while the resolution was worse with a increase in IPA %. From the experimental results, the desirable separation condition was 130 bar, 311.15 K and 4% IPA in CO$_2$. Compared to the asymmetric peak shape by liquid chromatography, that of supercritical fluid chromatography was symmetric which was a favorable condition for preparative separation.

• Bulletin of the Korean Chemical Society
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• v.25 no.12
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• pp.1807-1811
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• 2004

Supercritical fluid chromatography (SFC) was considered for separating racemic ibuprofen. The chromatographic column (3.9 ${\times}$ 150 mm) was packed with Kromasil$^{\circledR}$ CHI-TBB, and the mobile phase was supercritical carbon dioxide with modifier of IPA. The experimental variables were the content of IPA, and temperature and pressure of supercritical mobile phase. To determine the separation condition, the empirical equation of retention factor and resolution was proposed. In the case of retention factor, the empirical equation was in the form, $k\;=\;a{\rho}\;+b/F\;+\;c\;({\rho}/F)\;+\;d$. The empirical equation for resolution was proposed as a linear form, $R\;=\;a{\rho}\;+\;bF\;+\;c$.

• KSBB Journal
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• v.18 no.4
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• pp.261-265
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• 2003

Ibuprofen was analyzed by chiral high performance liquid chromatography. Retention behaviours of the standard mixtures of ibuprofen were investigated to obtain their acceptable resolution. A chromatographic column (3.9 ${\times}$ 300 mm) was packed by Kromasil CHI-TBB packings (10 $\mu\textrm{m}$) and n-hexane was used as a mobile phase with 0.1％ acetic acid and tert-butyl methyl ether. Isocratic elution of ibuprofen at 1.0 $m\ell$/min was performed by changing the mobile phase compositions. The experimental variables affecting the resolution were the compositions of mobile phase and chemical buffer (n-hexane and tert-butyl methyl ether). The resolution between the enantiomers were correlated into the several types of empirical equations including linear form, and their agreements between experimental data and calculated values were examined by the regression coefficient.

• Archives of Pharmacal Research
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• v.29 no.1
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• pp.108-111
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• 2006

The economic and effective method for preparation of R-(-)-ibuprofen by diastereomer crystallization was developed. R-(-)-ibuprofen was resolved from racemic ibuprofen by forming R-(-)ibuprofen-R-(+)-$\alpha$-methylbenzylamine diastereomeric salt with R-(+)-$\alpha$-methylbenzylamine and crystallization. The purity of R-(-)-ibuprofen-R-(+)-$\alpha$-methylbenzylamine diastereomeric salt was tested and confirmed using HPLC and $^1H-NMR$ method. The pure diastereomeric salt collected from repeated recrystallization was further fractionated by liquid-liquid extraction to the pure enantiomer without racemization. R-(-)-ibuprofen was recovered producing overall yield of 2.4% with the purity more than 99.97%.

• KSBB Journal
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• v.20 no.3
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• pp.244-249
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• 2005

Chiral separation of racemic ibuprofen was achieved on a Kromasil KR100-5CHI-TBB column. Some chromatographic parameters (resolution, number of theoretical plates, HETP, capacity factor) are calculated under different separation conditions such as change of mobile phase compositions (hexane / t-BME : 85 / 15, 75 / 15, 65 / 35, 55 /45) as well as acetic acid concentrations for adjusting pH (0.1 to 1 $v/v\%$). Flow rate versus number of theoretical plates and HETP were compared to evaluate column efficiency. To determine the adsorption isotherms, PIM (Pulsed Input Method) was carried out. At concentrations of racemic ibuprofen between 0.1 and 0.3 mg/ml, S- and R-ibuprofen have the same retention time of 4.48 and 5.81 min. Ibuprofen isotherms show a linear form under concentrations of 0.3 mg/ml with eluent (hexane / t-BME = 55 / 45).

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.219.1-219.1
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• 2003

$^1$H-NMR method for the determination of enantiomeric purity of (S)-(+)-ibuprofen was developed using (-)-cinchonidine as a chiral solvating agent. (S)-(+)-ibuprofen was prepared by optical resolution of racemic ibuprofen using preferential recrystallization method with (S)-(-)-${\alpha}$-methylbenzylamine and (R)-(-)-ibuprofen by semi-preparative chiral HPLC using chiral OD column and n-hexane/2-propanol/trifluoroacetic acid as a mobile phase. Several concentrations of synthetic mixture of (S)-(+)-ibuprofen and (R)-(-)-ibuprofen were added to the (-)-cinchonidine disolved in CDCl$_3$. (omitted)

• Journal of Microbiology and Biotechnology
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• v.18 no.3
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• pp.465-471
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• 2008

Highly active, stable, and magnetically separable immobilized enzymes were developed using carboxymethyl cellulose (CMC) and diethylaminoethyl cellulose DEAE-C; hereafter designated "DEAE" as supporting materials. Iron oxide nanoparticles penetrated the micropores of the supporting materials, rendering them magnetically separable. Lipase (LP) was immobilized on the surface of the supporting materials by using cross-linked enzyme aggregation (CLEA) by glutaraldehyde. The activity of enzyme aggregates coated on DEAE was approximately 2 times higher than that of enzyme aggregates coated on CMC. This is explained by the fact that enzyme aggregates with amine residues are more efficient than those with carboxyl residues. After a 96-h enantioselective ibuprofen esterification reaction, 6% ibuprofen propyl ester was produced from the racemic mixture of ibuprofen by using DEAE-LP, and 2.8% using CMC-LP.

• Biotechnology and Bioprocess Engineering:BBE
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• v.5 no.1
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• pp.53-56
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• 2000

A thermostable esterase from the hyper thermophilic archaeon Sulfolobus solfataricus was partially purified 590-fold with $16.2\%$ recovery. The partially purified esterase had a specific activity of $29.5\;{\mu}mol\;min^{-1}mg^{-1}$ when the enzyme activity was determined using p-nitrophenyl butyrate as a substrate. The apparent molecular weight was about 100 kDa, while the optimum temperature and pH for esterase were $75^{\circ}C$ and 8.0, respectively. The enzyme showed high thermal stability and solvent tolerance in comparison to its mesophilic counterpart. The enzyme also showed chiral resolution activity for (S)-ibuprofen, indicating that S. solfataricus esterase can be used for the production of commercially important chiral drugs.