• Biomolecules & Therapeutics
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• 제29권2호
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• pp.205-210
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• 2021

Over 30 million prescriptions of NSAIDs (non-steroidal anti-inflammatory drugs) are issued every year. Considering that these drugs are available without a prescription as over the counter (OTC) drugs, their use will be astronomical. With the increasing use of NSAIDs, their adverse effects are drawing attention. Especially, stomach bleeding, kidney toxicity, liver toxicity, and neurological toxicity are reported as common. Ibuprofen, one of the extensively used NSAIDs along with aspirin, can also induce liver toxicity, but few studies are addressing this point. Here we examined the liver toxicity of ibuprofen and investigated whether co-exposure to ethanol can manifest synergistic effects. We employed 2D and 3D cultured human hepatoma cells, HepG2 to examine the synergistic hepatotoxicity of ibuprofen and alcohol concerning cell viability, morphology, and histology of 3D spheroids. As a result, ibuprofen and alcohol provoked synergistic hepatotoxicity against hepatocytes, and their toxicity increased prominently in 3D culture upon extended exposure. Oxidative stress appeared to be the mechanisms underlying the synergistic toxicity of ibuprofen and alcohol as evidenced by increased production of ROS and expression of the endogenous antioxidant system. Collectively, this study has demonstrated that ibuprofen and EtOH can induce synergistic hepatotoxicity, providing a line of evidence for caution against the use of ibuprofen in combination with alcohol.

• Korean Chemical Engineering Research
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• 제51권6호
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• pp.685-691
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• 2013

이부프로펜은 비스테로이드성 소염진통제(Non-Steroidal Anti-Inflammatory Drugs; NSAIDs)의 대표적인 성분이다. 이부프로펜은 결정성이 크기 때문에 난용성이며, 따라서 생체이용률(bioavailability)도 낮다. 이와 같은 난용성을 개선하기 위해서는 이부프로펜의 입도를 감소시킬 필요가 있다. 본 연구의 목적은 이부프로펜의 분쇄조건을 최적화하는데 있다. 이부프로펜을 분쇄하기 위하여 유성밀을 사용하였으며, Box-Behnken 방법을 이용하여 분쇄변수들의 최적조건을 구하였다. 이부프로펜 분쇄생성물의 물성을 조사하기 위하여 입도, 결정크기 및 인장강도 측정에는 각각 입도분석기, XRD, tensile/compression tester를 사용하였다. 분쇄 최적조건은 밀회전수는 290 rpm, 시료장입량은 24.6 g, 분쇄시간은 10분이었으며, 이 조건에서 이부프로펜 분쇄생성물의 입도는 $13.5{\mu}m$이었다. 이부프로펜은 분쇄 후 결정크기가 감소하였다. 이부프로펜 분쇄생성물의 정제의 상대밀도가 0.85~0.90인 범위에서 그 정제의 인장강도는 $12{\sim}14Kg_f/cm^2$ 이었다.

• 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)

• Clinical and Experimental Pediatrics
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• 제51권9호
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• pp.956-963
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• 2008

목 적 : Indomethacin은 동맥관 개존증의 예방 및 치료에 널리 사용되고 있다. 그러나 indomethacin은 신부전, 괴사성 장염, 뇌실내 출혈, 위장관 출혈 등의 합병증을 유발한다. Ibuprofen은 동맥관 개존증을 치료하는데 indomethacin 만큼 효과적이며 신장, 장간막, 뇌혈류에 영향을 주지 않는다. 동맥관 치료에 있어서 경구용 ibuprofen의 효과가 indomethacin과 동일하다면 경구용 ibuprofen은 투여가 간단하고 비용이 저렴한 장점이 있다. 이 연구에서는 미숙아 동맥관 개존증의 치료에서 indomethacin과 경구용 ibuprofen의 효과와 부작용을 비교하였다. 방 법 : 무작위 이중 맹검법으로 미숙아 중 호흡곤란 증후군을 진단받고 심초음파에서 혈역학적으로 의미 있는 동맥관 개존증이 확인된 환아 34명을 대상으로 18명에게는 indomethacin 정맥 투여나 ibuprofen 경구 투여를 시행하였다. 심초음파를 실시하는 소아심장 전문의는 환아의 투약 종류를 모르는 상태에서 연구가 진행되었으며 동맥관 폐쇄율, 추가적인 약물 치료나 수술의 필요성, 약물의 부작용 및 환아의 임상 경과를 비교하였다. 결 과 : 동맥관 폐쇄율은 indomethacin군은 18명 중 16명(88.9%), ibuprofen군은 16명 중 14명(87.5%)이었다(P>0.05). 2차로 약물 치료가 필요한 환아는 indomethacin군은 3명, ibuprofen군에서는 4명이었다(P>0.05). 3명(indomethacin군에서 1명, ibuprofen군에서 2명)은 수술적 치료를 시행하였다(P>0.05). 약물 치료 후의 임상경과와 부작용은 두 군 간에 통계학적으로 유의한 차이가 없었다. 결 론 : 경구용 ibuprofen은 indomethacin에 비해 효능과 부작용 및 임상 경과에 차이가 없고 투여가 간단하고 비용 면에서는 월등한 이득이 있으므로 호흡곤란 증후군을 가진 미숙아의 동맥관 개존증 치료에 있어서 경구용 ibuprofen의 보편적 사용을 고려할 수 있을 것이다.

• Advances in Traditional Medicine
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• 제8권2호
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• pp.178-186
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• 2008

In this study, ionotropic gelation method was used for the preparation of ibuprofen-loaded calcium alginate (CALG) and ethylenediamine (EDA) treated calcium alginate (EDA-CALG) microspheres. The effect of EDA-treatment on drug entrapment efficiency, particle size, morphology, swelling behavior and in vitro release characteristics of the microspheres was investigated by varying its concentration from 0.5 to 2% (v/v). The reduction in drug entrapment efficiency by a maximum of 44.60% was noted for EDA-CALG microspheres compared to untreated CALG microspheres. The particle size and swelling index of EDA-CALG microspheres were reduced with increasing EDA concentration. All the microspheres were observed to retain their spherical shapes with rough surfaces. EDA-CALG microspheres prepared using 1% and 2% v/v EDA, released almost all of its content within 7 h in pH 6.8 phosphate buffer, however, CALG microspheres were found to release the same within 3 h. The intensity of melting endothermic peak of ibuprofen reduced significantly at lower drug load as experienced from DSC thermograms. The FT-IR spectrum of pure ibuprofen, ibuprofen-loaded CALG and EDA-CALG microspheres showed the characteristic band of C = O stretching vibration of ibuprofen. Hence, this study revealed that EDA can be employed for the preparation of ibuprofen-loaded CALG microspheres to retard the drug release to some extent.

• Journal of Pharmaceutical Investigation
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• 제25권2호
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• pp.153-161
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• 1995

Alginic acid is a hydrophilic , colloidal polysaccharide obtained from cell wall of seaweed or brown algae and has a broad range of applications. Alginlc acid becomes alginate gel bead due to its cation-induced gelation. Dried alginate beads can be reswollen according to environmental pH. The purpose of this paper is to explore the possible applicability of alginate beads as an oral controlled release system of ibuprofen. In this experiment ibuprofen was incorporated in alginate beads and alginate beads were treated with various methods. Ibuprofen release from alginate beads in phosphate buffer (pH 7.4) was laster than in distilled water and dilute HCl. The release of ibuprofen was more sustained in bead than simple mixture and coprecipitate of ibuprofen and sodium alginate. The dissolution rate of ibuprofen was decreased in using of bead that hardened with formaldehyde. The dissolution rate of the drug from the bead was the fastest in 12 hour dried beads, 1.5%-sodium alginate concentration and 1%-calcium chloride concentration. Sodium alginate bead can be used as a sustaind release drug delivery system of water-insoluble drugs.

• Journal of Pharmaceutical Investigation
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• 제23권1호
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• pp.11-18
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• 1993

Inclusion complex of ibuprofen with $2-Hydroxypropyl-{\beta}-cyclodextrin\;(HP-{\beta}-CD)$ in aqueous solution and in the solid state was evaluated by the solubility method and the instrumental analysis such as infrared spectroscopy, thermal analysis and x-ray diffractometry. The aqueous solubility of ibuprofen was increased linearly with the increase in the concentration of $HP-{\beta}-CD$, showing an $A_L$ type phase solubility diagram. The results showed that the dissolution rate of ibuprofen was significantly increased by complexation with $HP-{\beta}-CD$. $Ibuprofen-HP-{\beta}-CD$ complex enhanced the mean plasma concentration levels and the area under plasma concentration-time curve after oral administration compared to those of the drug alone. It is concluded that the complex of ibuprofen with $HP-{\beta}-CD$ increases the dissolution rate and improves the bioavailability of the ibuprofen by the formation of a water-soluble complex.

• 대한기계학회논문집A
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• 제29권7호
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• pp.1022-1027
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• 2005

In this study, ball milling process was applied to reduce the particle size of bio-material down to submicron size. The material used was Ibuprofen. The ball milling was performed at low temperature of about $-180^{\circ}C$. The effect of processing conditions (milling time, milling speed) on the particle size was determined. The results showed that the degree of crystallite of Ibuprofen was slightly reduced by the ball milling process. The results also showed that the size of Ibuprofen was significantly reduced by the ball milling process. The effect of milling time was significant within the milling time of six hours while it was small thereafter.

• Journal of Pharmaceutical Investigation
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• 제24권3호
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• pp.115-129
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• 1994

In the present study, quantitative and qualitative histology was used to assess the effects of ibuprofen suppositories with various treatments on the rectal mucosa of rats. Two suppositories were prepared with Witepsol W35 and compared with two commercial ibuprofen suppositories Reference I (Showa Pharm.ind., Tokyo, Japan), Reference II (P.Pharm., Seoul, Korea). Single and multiple dose(dosing interval 4 hr, n=4) studies were conducted. All suppositories significantly increased epithelial cell loss, but the extent of rectal irritation was variable. These studies showed that the incorporation of ibuprofen into the suppository bases increases the morphological change in rectal tissue both for the single and multiple administrations of suppositories, but which was significantly recovered within 24 hr although the interanimal variability in scores was very substantial. Multiple administration of ibuprofen suppositories caused significant damage to rectal mucosa, but it must be considered that these were under the severe condition, that is, interval of administration (4 hr) was three times shorter than normal interval of administration and dose was fifteen times larger than usual human dose. Aluminum oxide $(Al_2O_3)$, a dispersing agent, slightly increased the irritation of rectal mucosa in rats at 5 hr and 24 hr after multiple administration, but it was possible to ignore the difference of irritation in the data at 5hr and 24hr after single administration. Finally, it was concluded that Witepsol W35 and ibuprofen had a slight rectal mucosa-irritating effect on the usual human dose, and ibuprofen suppositories prepared with Witepsol W35 or Witepsol W35, $Al_2O_3$ showed almost similar extent of rectal irritation with commercial ibuprofen products.

• 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.