• Journal of Pharmaceutical Investigation
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• v.37 no.5
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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.

• YAKHAK HOEJI
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• v.25 no.3
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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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• 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.

• Archives of Pharmacal Research
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• v.29 no.6
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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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• v.33 no.1
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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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• v.44 no.3
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• pp.248-253
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• 2006

In order to develope an efficient drug delivery system, experimental researches on the supercritical impregnation of ibuprofen onto mesoporous silica, MCM-41,and its drug release characteristics were performed. Supercritical carbon dioxide was adapted as an alternative solvent as it is harmless and able to avoid defects of organic solvents in drug manufacturing processes. The procedure was composed of three steps, that is, as hydrothermal synthesis of MCM-41, supercritical impregnation of ibuprofen onto MCM-41 and release of impregnated ibuprofen. Supercritical impregnation reached equilibrium within 2 h for all cases of this research and the amount of equilibrium impregnation increased with solubility of ibuprofen in supercritical carbon dioxide. Release profiles of impregnated ibuprofen showed a similar behavior for all MCM-41 with different impregnated ibuprofen.

• Neonatal Medicine
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• v.18 no.2
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• pp.228-233
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• 2011

Purpose: The aim of our study was to compare the efficacy and safety of ibuprofen and indomethacin in the prophylaxis of patent ductus arteriosus (PDA) in preterm infants and to determine whether ibuprofen could be an alternative agent in prophylactic use. Methods: A retrospective study including 37 preterm infants <1,500 g of birth weight, <34 weeks of gestation, whom were administrated indomethacin (n=17; January 2009-December 2009) or ibuprofen (n=20; January 2010-February 2011) within 24 hr after birth was conducted. The rate of ductal closure, need for surgical ligation, clinical outcomes such as necrotizing enterocolitis, intraventricular hemorrhage, bronchopulmonary dysplasia, retinopathy of prematurity (ROP) and death rate were compared. Results: There were no statistically significant differences between the two groups in mean gestational age, mean birth weight, Apgar score, sex, type of delivery, maternal dexamethasone treatment, frequency and duration of ventilator and surfactant treatment. The closure of PDA on day 7 of life was in 19 of 20 infants of the ibuprofen group and 13 of 17 infants of the indomethacin group (P=0.159). Between the two groups, there were no significant differences with respect to clinical outcomes. Conclusion: Ibuprofen has similar effects to indomethacin in the rate of PDA closure. Our study demonstrates that prophylactic ibuprofen is relatively effective without significant differences with respect to clinical outcomes compared with indomethacin. Therefore, ibuprofen may be used as an alternative agent in the prophylaxis of PDA in preterm infants.

• Journal of Pharmaceutical Investigation
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• v.24 no.3
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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.

• YAKHAK HOEJI
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• v.45 no.6
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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.

• Proceedings of the Korean Society of Precision Engineering Conference
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• 2004.10a
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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