• Journal of Pharmaceutical Investigation
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• 제37권5호
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• pp.269-273
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• 2007

Poorly water-soluble ibuprofen and ethanol can be encapsulated in gelatin microcapsule by spray drying technique. To select an optimal formula of ibuprofen-loaded gelatin microcapsule which increased the ethanol content and ibuprofen solubility with the decreased amount of gelatin in the microcapsules, in this study, the effect of gelatin, ibuprofen and sodium lauryl sulfate on the ibuprofen solubility and the amount of ethanol and ibuprofen encapsulated in the gelatin microcapsule were investigated. Ibuprofen solubility and the amount of ethanol encapsulated increased as gelatin and sodium lauryl sulfate increased, reached maximum at 4% and 0.6%, respectively and then followed a rapid decrease. Furthermore, the ibuprofen solubility and the encapsulated ibuprofen content increased as the amount of ibuprofen increased, reaching maximum at 0.5% and beyond that, there was no change in the solubility and ibuprofen content. However, the encapsulated ethanol content remained same irrespective of the amount of ibuprofen. On the basis of increased ibuprofen solubility, our results showed that the formula of ibuprofen-loaded gelatin microcapsule at the ratio of gelatin/ibuprofen/sodium lauryl sulfate/water/ethanol of 4/0.5/0.6/30/70 with ibuprofen solubility of about $290\;{\mu}g/mL$ and ethanol content of about $160\;{\mu}g/mg$ could be a potential oral delivery system for poorly water-soluble ibuprofen.

• 약학회지
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• 제25권3호
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• pp.109-114
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• 1981

The authors investigated drug interaction of ibuprofen and prednisolone in antiinflammatory and antipyretic activities. We have found significant differences of the antiinflammatory and antipyretic activities between single and concurrent administration of ibuprofen and prednisolone, using Sprague-Dawley Strain rats, carrageenin as a phlogistic agent and brewer's yeast as a fever inducing agent. 1) Ibuprofen(20mg/kg) was administered to the rats orally and resulted in significant reduction of (31.70 %) the swelling of rat paw induced by carrageenin, 2) prednisolone (9mg/kg) showed significant reduction of (45.76%) the swelling, 3) concurrent administration of ibuprofen (20mg/kg) and prednisolone (9mg/kg) also reduced (57.40%) the swelling. In ibuprofen (125mg/kg) administration, the inhibition rate of edema was 39.32% and in prednisolone (1mg/kg) administration, the rate was 39.04%. In concurrent administration of ibuprofen (125mg/kg) and prednisolone (1mg/kg), the inhibition rate of edema was 63.09%. Concurrent administration of ibuprofen and prednisolone showed more anti-inflammatory effects than single administration of ibuprofen and prednisolone respectively. Prednisolone itself did not show antipyretic effect, but concurrent administration of ibuprofen and prednisolone showed more antipyretic effects than ibuprofen single administratron.

• KSBB Journal
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• 제17권6호
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• pp.543-548
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• 2002

Candida rugosa lipase를 이용하여 효소 농도, 반응온도, 알콜 농도 및 종류 등의 반응조건에 따른 racemic ibuprofen 에스테르화 반응의 초기반응속도, 전환율 그리고 입체 선택성 을 조사하였다. 제조된 S-(+)-ibuprofen alkyl ester는 황산을 촉매로 하는 가수분해반응에 의해 순수한 S-(+)-ibuprofen으로 전환되었다. 에스테르화 반응에서는 반응온도 6$0^{\circ}C$에서 최대 활성을 보였으며, 그 이상의 온도에서는 효소의 활성 저하로 전환율과 enantiomeric excess값이 동시에 현격하게 감소하는 경향을 보였다. 알코올 농도가 증가할수록 알콜의 효소반응 저해제작용으로 인하여 초기반응속도가 감소하는 경향을 보였으며, 최종 전환율은 Ibuprofen와 Alcohol의 몰 비가 1/1에서 최고 값을 나타냈다. 알콜 종류에 따른 알코올 체인 길이가(C$_2$~C$_{10}$) 증가할수록 전환율은 증가하였는데, 특히 알코올 체인길이가 가장 큰 데칸올이 가장 높은 전환율을 보였다. 반응온도가 6$0^{\circ}C$ 이상의 높은 경우를 제외하고 에스테르화 반응 조건에 따라 입체 선택성 즉 enantiomeric excess의 큰 변화는 없었다. 화학적 가수분해 반응은 비교적 짧은 반응시간(3시간)내에 평형반응에 도달하였으며 알코올 체인 길이에 관계없이 거의 95% 이상의 높은 전환율 및 입체 선택성을 나타냈다. Lipase에 의한 ibuprofen 에스테르화 반응의 최적 조건과 화학적인 가수분해 반응을 통해서 racemic ibuprofen으로부터 높은 수율의 S-(+)-ibuprofen을 확보할 수 있었다.

• Archives of Pharmacal Research
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• 제29권6호
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• pp.520-524
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• 2006

Ibuprofen-loaded gelatin microcapsule, a solid form of microcapsules simultaneously containing ethanol and ibuprofen in water-soluble gelatin shell was previously reported to improve the dissolution of drug. In this study, to retard the initial high dissolution of ibuprofen from gelatin microcapsule, the ibuprofen-loaded cross-linked gelatin microcapsule was prepared by treating an ibuprofen-loaded gelatin microcapsule with glutaraldehyde and its dissolution was evaluated compared to ibuprofen powder and gelatin microcapsule. The ibuprofen-loaded crosslinked microcapsule treated with glutaraldehyde for 10 and 60 sec gave significantly higher dissolution rates than did ibuprofen powder. Furthermore, the dissolution rate of ibuprofen from the cross-linked microcapsule treated for 10 sec was similar to that from gelatin microcapsule. However, the dissolution rate of ibuprofen from the cross-linked microcapsule treated for 60 sec decreased significantly compared to gelatin microcapsule, suggesting that the treatment of gelatin microcapsule with glutaraldehyde for 60 sec could cross-link the gelatin microcapsule. Furthermore, the cross-linking of gelatin microcapsule markedly retarded the release rate of ibuprofen in pH 1.2 simulated gastric fluid compared to gelatin microcapsule. However, the cross-linking of gelatin microcapsule with glutaraldehyde hardly changed the size of gelatin microcapsules, ethanol and ibuprofen contents encapsulated in gelatin microcapsule. Thus, the ibuprofen-loaded cross-linked gelatin microcapsule could retard the initial high dissolution of poorly water-soluble ibuprofen.

• Journal of Pharmaceutical Investigation
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• 제33권1호
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• pp.57-60
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• 2003

To enhance the solubility of poorly water-soluble ibuprofen with poloxamer and menthol, the effects of menthol and poloxamer 188 on the aqueous solubility of ibuprofen were investigated. In the absence and presence of additives such as ethanol and poloxamer 188, the solubility of ibuprofen increased until the ratio of menthol to ibuprofen increased from 0:10 to 4:6 followed by an abrupt decrease in solubility above the ratio of 4:6, indicating that 4 parts of ibuprofen formed eutetic mixture with 6 parts of menthol. In the presence of poloxamer, the solutions with the same ratio showed abrupt increase in the solubility of ibuprofen. Furthermore, in the presence of poloxamer, the solution with ratio of 4:6 showed more than 2.5- and 6-fold increase in the solubility of ibuprofen compared with that without additives and that without menthol, respectively. The solution with menthol/ibuprofen ratio of 1:9 and higher than 15% poloxamer 188 showed the maximum solubility of ibuprofen, 1.2 mg/ml. Thus, menthol gave the greatly enhanced solubility of ibuprofen with poloxamer 188.

• Korean Chemical Engineering Research
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• 제44권3호
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• pp.248-253
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• 2006

효율적인 약물 전달 시스템을 개발하기 위한 연구의 일환으로, 초임계 상태에서 mesoporous silica인 MCM-41에 항염증제 ibuprofen을 함침시키고, 그 방출효과를 실험적으로 조사하였다. 초임계 용매로는 기존의 약물 처리 공정에 사용되는 유기용매의 단점을 보완할 수 있는 무독성의 초임계 이산화탄소를 선택하였다. 실험은 수열합성법에 의한 MCM- 41의 합성, 초임계 이산화탄소에 의한 MCM-41에의 ibuprofen 함침 및 함침된 ibuprofen 용출의 세 공정으로 구성하였다. 초임계 함침 공정의 함침평형에 도달하는 시간은 본 연구의 조건 범위에서 약 2h 정도였으며, 평형 함침량은 초임계 이산화탄소에 대한 ibuprofen의 용해도 증가에 따라 증가하였다. Ibuprofen의 용출속도는 함침된 ibuprofen의 함량에 무관하게 유사한 형태의 용출 특성을 나타내었다.

• Neonatal Medicine
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• 제18권2호
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• pp.228-233
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• 2011

목적: Indomethacin은 미숙아 동맥관 개존증의 예방적 용법 및 치료적 용법에 사용되어 왔다. 하지만 최근에는 indomethacin의 국내 보급이 중단됨에 ibuprofen이 사용되고 있다. Ibuprofen은 동맥관 폐쇄에 indomethacin만큼 효과적이며 부작용은 적은 것으로 알려져 있다. 그러나 ibuprofen의 예방적 용법에 관한 연구는 많지 않다. 본 연구에서는 미숙아에서 동맥관 개존증의 예방적 치료에 대한 ibuprofen의 효과와 안정성을 indomethacin과 비교하여 분석하고자 하였다. 방법: 2009년 1월부터 2009년 12월, 그리고 2010년 1월부터 2011년 2월까지 두 기간동안 3개의 참여 대학병원 신생아 중환자실에 입원한 34주 미만, 1,500 g 미만의 신생아 중에서 생후 24시간 이내에 indomethacin이나 ibuprofen이 예방적 목적으로 투여된 환자를 대상으로 하여 의무기록을 후향적으로 검토하였다. 두 군간의 동맥관 폐쇄에 대한 효과와 주산기 합병증의 발생 정도를 조사하였다. 결과: 두 군간에 환아의 성별, 재태 연령, 출생체중, 분만 방법, 1분 및 5분 Apgar 점수, 산모의 steroid 사용 여부, 폐 표면활성제 사용 여부 및 인공호흡기 사용여부 및 사용기간에 있어 유의한 차이는 없었다. 생후 7일에 시행한 심초음파 검사에서 indomethacin군은 17명 중 13명, ibuprofen군은 20명 중 19명이 동맥관의 폐쇄를 보였다. 총 입원 기간 외에 주산기 합병증의 빈도는 두 군간의 유의한 차이가 없었다. 결론: Ibuprofen의 예방적 사용은 동맥관 폐쇄에 효과적이며 주산기 합병증 측면에서 유의한 부정적인 차이가 없었다. 따라서 indomethacin을 대체하여 ibuprofen의 사용을 고려해 볼 수 있겠다.

• Journal of Pharmaceutical Investigation
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• 제24권3호
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• pp.145-153
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• 1994

Ibuprofen is an effective non-steroidal anti-inflammatory drug (NSAID), but it has several limitations in clinical application because of low solubility in water and gastrointestinal irritation. A water-soluble salt of ibuprofen, ibuprofen Iysinate, has been synthesized to overcome these shortcomings, and it was formulated as suppository for rectal administration. Witepsol and polyethylene glycols were employed as suppository bases for either ibuprofen or ibuprofen Iysinate, in order to compare the bioavailability in rabbits. The plasma concentrations of ibuprofen were assayed by HPLC after a rectal administration of ibuprofen and ibuprofen Iysinate, respectively. In addition to the comparison of two suppository bases, the other factors which affect on rectal absorption were also evaluated, especially in the point of not only particle size and shape of ibuprofen Iysinate but also effects of additives such as stearic acid, cetyl alcohol and capric acid. And pharmacokinetic parameters such as AUC, $C_{max}$, and $T_{max}$ were also compared. In conclusion, spray-dried ibuprofen Iysinate which was polyporous and spherical shape gave an increased absorption from the rectal formulations with Witepsol Hl5 and stearic acid.

• 약학회지
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• 제45권6호
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• pp.634-640
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• 2001

Ibuprofen is one of the nonsteroidal anti-inflammatory drugs (NSAID) and has shown antiinflammatory; antipyretic, and analgesic activity in both animals and humans. But it causes gastric mucosal abnormalities including edema, erythema, and submucosal petechial hemorrhages and erosin in human. In addition, based on the pharmaceutical point of view the compression and dissolution ability of ibuprofen is known as poor. Therefore we studied to develop novel formulation containing water-insoluble drug, ibuprofen, using microemulsion consisting of surfactant, oil phase, and water phase was prepared for the purpose of increasing its bioavilability The physicochemical properties such as particle size, dissolution rate, solubility of ibuprofen in the system were determined. After oral administration of ibuprofen containing the microemulsion system, to Sprague-Dawley rats, pharmacokinetic parameters were also obtained. For the formulation in the study, oleic acid, linoleic acid, and several kinds of glycerides and triglycerides were used as an oil phase with several surfactants. Diethylene glycol monoethyl ether (Transcuto $l^{ }$) or saturated polyglycolized glycerides (Labrafil $^{ }$)as surfactant was used, the domain of microemulsion was wide. The diameter of o/w microemulsion was ranged from 90 to 220 nm. Microemulsion, prepared with unsatulated polyglycolized glycerides (Labrafil $^{ }$) and the 2 : 1 molar mixture of diethylene glycol monoethyl ether (Transcuto $l^{ }$)/polyoxyethylene(4) lauryl ether (Bri $j^{ }$ 30) , is expected to be promising system that increased the bioavilability of ibuprofen.ibuprofen.

• 한국정밀공학회:학술대회논문집
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• 한국정밀공학회 2004년도 추계학술대회 논문집
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• pp.442-446
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• 2004

Reducing the particle size of drug materials down to submicron is an important matter in pharmaceutical industry. Cryogenic milling technology is one of the mechanical milling processes, which is mostly utilized in refining grain size of metal and ceramics at extremely low temperature environment. This technique has not been readily studied in application to medical and biotechnology. This paper, therefore, describes the application of cryogenic milling process to reduce particle size of Ibuprofen. The shape and size of the Ibuprofen particle before and after the cryogenic ball milling process were analyzed. XRD analysis was performed to examine a change in crystallinity of Ibuprofen by the cryogenic ball milling process. The results showed that the size of Ibuprofen particles was reduced to 1/10 or less of its initial size. The results also showed that the degree of crystallinity of Ibuprofen was slightly reduced after cryogenic ball milling with nitrogen