• Archives of Pharmacal Research
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• 제29권1호
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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%.

• Archives of Pharmacal Research
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• 제27권8호
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• pp.820-824
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• 2004

An optical purity test was indirectly performed on (S)-ibuprofen as its diastereomeric (R)-(+)-1-phenylethylamide derivative using achiral gas chromatography (GC). The method for the determination of trace (R)-ibuprofen (optical impurity), within the range 1.0 to 50 ng, from a racemic ibuprofen standard was linear (r＝0.9997) with acceptable precision (％ $RSD{\leq}5.3$) and accuracy (％ RE＝0.7~-3.9). Similar results were obtained with the method validation for the quantification of (S)-ibuprofen within the range 0.1 to 2.0 $\mu\textrm{g}$ using a (S)-ibuprofen stan-dard. When applied to seven different commercial (S)-ibuprofen products, their optical purities (98.7~99.1％) were determined with good precision (％ $RSD{\leq}4.0$).

• Journal of Pharmaceutical Investigation
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• 제27권4호
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• pp.279-286
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• 1997

In order to formulate 2% ibuprofen solution, the effects of various solublizing agents, such as cosolvents (propylene glycol, polyethylene glycol, glycerin), a complexing agent $(CELDEX{\circledR}\;CH20)$, surfactants $(Poloxamers\;and\;Cremophor{\circledR}\;RH40)$ on the solubility of ibuprofen in aqueous solution were evaluated. Among them, Poloxamer 407 and $Cremophor{\circledR}$ RH40 showed the excellent capacity on the solubilization of ibuprofen. After 2% ibuprofen solution of choice were administered orally to rats, in reference to a 2% ibuprofen syrup in the market, the pharmacokinetic parameters were determined. The absorption rate of ibuprofen from the solution was higher than that from the suspension.

• Korean Chemical Engineering Research
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• 제47권1호
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• pp.54-58
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• 2009

Ketoprofen과 Ibuprofen은 비스테로이드 계통의 진통 및 소염제로서 관절염 등을 위한 진통제나 해열제로 이미 널리 사용되고 있다. 그러나 이 두 물질이 치료약으로 사용될 때 (S)-ketoprofen과 (S)-ibuprofen은 약리학적으로 항염증 작용을 하며 (R)-ketoprofen과 (R)-ibuprofen은 약효가 없거나 부작용을 일으키는 문제점을 가지고 있다. 본 연구에서는 Ketoprofen과 Ibuprofen을 Kromasil HPLC 칼럼을 사용하여 이동상 조성비(hexane/t-BME/acetic acid)와 온도 변화($25{\sim}55^{\circ}C$)가 분리에 미치는 영향을 실험하였다. 분리특성은 선택도, 분리도, 이론단수 그리고 용량인자와 절대온도의 역수사이의 관계에서 계산된 엔탈피 변화 ${\Delta}H$에서 Ketoprofen과 Ibuprofen의 kromasil HPLC column 고정상과의 상호작용의 크기를 열역학적으로 검토하였다. 온도 $25^{\circ}C$, 이동상 조성비(hexane/t-BME/acetic acid) 80/20/0.1에서 선택도, 분리도, 이론단수 엔탈피 수치가 높게 나타났다.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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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)

• KSBB Journal
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• 제20권3호
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• pp.244-249
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• 2005

Kromasil HR100-5CHI-TBB 칼럼을 사용하여 HPLC를 통한 비스테로이드 계통의 진통 및 소염제인 racemic ibuprofen의 분리특성을 연구하였다. 이동상의 조성비 변고에 따른 분리도 (resolution), 이론단수 (number o( theoretical plates), 이론단 높이 (HETP: Height Equivalent to a Theoretical Plate), 용량인자 (capacity factor)를 계산하고, 그 결과 정성분석 기준치 이상의 분리도를 갖고 분리시간을 단축할 수 있는 hexane /t-BME의 조성이 55 / 45일 때 $1\%$의 acetic acid를 첨가했을 때의 용매를 최적의 이동상으로 결정했다. 유속에 따른 칼럼의 효율을 비교하기 위한 실험을 통해 유속의 상승은 칼럼의 효율의 감소를 야기하고, 분리도를 감소시킴을 보였다. PIM (Pulsed Input Method)을 사용하여 분석한 결과 ibuprofen 의 농도가 증가할수록 Langmuir 등온흡착식을 따르는 비선형 거동을 보임을 증명하였고, 그 결과 등온흡착식을 결정하였다. 등온흡착식은 S-form과 R-form의 경우 각각 $C_{S,S}=\frac{1.178C_{M,S}}{1+0.019C_{M,S}},\;C_{S,R}=\frac{1.866C_{M,S}}{1+0.017C_{M,S}}$로 결정하였다.

• KSBB Journal
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• 제21권3호
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• pp.224-229
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• 2006

전산모사 프로그램인 FEMLAB을 이용하여 chiral center를 가지고 있는 racemate인 ibuprofen의 R-form과 S-form의 분리 전산모사 결과와 Kromasil KR100-5CHI-TBB 칼럼을 사용하여 HPLC를 통한 실험데이터를 비교 분석하였다. Hexane/t-BME/acetic acid(45:55:1 v/v%)의 이동상의 조건에서 이론단수(number of theoretical plates), 이론단높이(HETP; Height Equivalent to a Theoretical Plate)을 구하여 축방향 확산계수($Deff_i$)를 계산하였다. PIM(Pulsed Input Method)을 사용하여 분석한 결과 ibuprofen의 농도가 증가할수록 Langmuir 등온흡착식을 따르는 비선형 거동을 보였고, 각 농도에서의 체류시간($t_R$)과 phase ratio를 이용하여 비경쟁적 Langmuir 등온흡착식의 매개변수를 추산하였고, 이 매개변수를 이용하여 경쟁적 Langmuir 등온흡착식을 결정하였다. 실험을 통해 얻은 데이터를 FEMLAB 적용하여 등온흡착식의 변화에 따른 용리띠의 변화와 두 성분이 컬럼을 이동하는 동안 두 성분간 분리 과정을 관찰하였다. Ibuprofen의 농도, 유속을 변화시키면서 실험결과와 전산모사결과를 비교한 결과 실험결과와 전산모사결과가 비슷한 경향성을 보였다. 이와 같이 FEMLAB 전산모사 프로그램의 실험적용 가능성을 확인하였고. 실험과 일치하는 전산모사데이터를 얻기 위해서 고정상내의 세공에서의 물질전달을 포함하는 물질수지식의 적용과 비선형 흡착평형식에 대한 좀 더 정확한 식이 요구된다.

• 폴리머
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• 제37권3호
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• pp.288-293
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• 2013

A group of molecularly imprinted polymers (MIPs) with specific recognition for chiral (S)-ibuprofen were successfully prepared based on hydrogen bonds, utilizing ${\alpha}$-methacrylic acid as a functional monomer. The IR analysis of MIPs showed that the blue- and red-shifted hydrogen bonds were formed between templates and functional monomers in the process of self-assembly imprinting and re-recognition, respectively. According to UV-Vis analysis, we found that the ratio of host-guest complexes between template molecule and functional monomer was 1:1. The effect of cross-linker's quantity on the polymerization was studied by transmission electron microscope (TEM). The adsorption selectivity experiments indicated that MIPs exhibited higher selectivity to (S)-ibuprofen than those to ketoprofen and (R)-ibuprofen, (S)-ibuprofen's structural analogs.

• Bulletin of the Korean Chemical Society
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• 제25권12호
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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, $R\;=\;a{\rho}\;+\;bF\;+\;c$.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.223.3-224
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• 2003

Chiral discrimination of ibuprofen by $^1$H-NMR using several chiral solvating agents such as (-)-brucine, (-)-cinchonidine, (1R, 2S)-(-)-ephedrine, (S)-(-)-${\alpha}$- methylbenzylamine, (-)-strychnine and L-(-)-tryptophane was investigated. Racemic ibuprofen treated with one equivalent of chiral solvating agent was preferentially crystallized. Chiral purity of each precipitates was measured by chiral HPLC and chemical shift differences(ΔΔ$\delta$) was calculated. Eventhough (S)-(-)-${\alpha}$-methylbenzylamine was most effective for the preferential recrystalization of (S)-(+)-ibuprofen, chemical shift differentiation ability was weak. (omitted)