Motrin
Solid-state interaction of magnesium oxide and ibuprofen to form a salt.

Kararli TT, Needham TE, Seul CJ, Finnegan PM.

G. D. Searle & Co., Product Development, Skokie, Illinois 60077.

During formulation development work involving ibuprofen, a solid-state interaction between MgO and ibuprofen was observed. In this study the interaction of MgO and ibuprofen was investigated for 1:1 and 2:1 M mixtures of ibuprofen and MgO, which had been stored at 55 degrees C, using the differential scanning calorimetric (DSC), thermogravic analysis (TGA), and multiple internal reflectance infrared (MIR) techniques. Evidence for the reaction was the disappearance of the melting endotherm at 79 degrees C and appearance of a new endotherm at 161 degrees C after less than 1 day of storage at 55 degrees C and, also, the change in the physical appearance of the mixtures. Comparison of the DSC, TGA, and MIR data for the reacted ibuprofen and MgO mixtures and synthetic Mg(ibuprofen)2 indicated that MgO and ibuprofen react to form the Mg salt of ibuprofen. The interaction of ibuprofen and MgO was also studied at 30 and 40 degrees C, using 1:1 M mixtures. At 30 degrees C no significant interaction was observed for up to 80 days; however, at 40 degrees C a reaction was evident on day 1. NaHCO3, K2CO3 1.5H2O, CaO, and Mg(OH)2 also showed solid-state reactions with ibuprofen. MgCl2 and Al(OH)3 did not show this reaction.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2813278&dopt=Abstract ibuprofen Motrin



Motrin
Orally and parenterally administered ibuprofen for postoperative adhesion prevention.

De Leon FD, Odom J, Hudkins P, Vijayakumar R, Heine MW.

Adhesion formation was examined in 45 rats that were divided into five groups of 9 animals each: control, oral ibuprofen, intramuscular ibuprofen, intraperitoneal 32% dextran 70, and oral ibuprofen plus intraperitoneal 32% dextran 70. Four weeks after receiving a standard injury, all the animals were killed and the adhesions scored blindly. Both the oral and intramuscular ibuprofen groups had significantly less severe adhesion formation (P less than .01) when compared to the control group. Although 32% dextran 70 alone showed no beneficial effect in reducing adhesions, the combination of oral ibuprofen and 32% dextran 70 had the least adhesion formation (P less than .002) when compared to the control group. Oral and intramuscular ibuprofen seem to be equally efficient in reducing postoperative adhesions. Furthermore, the combination of oral ibuprofen and 32% dextran 70 appears to have a synergistic effect.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2433440&dopt=Abstract ibuprofen Motrin



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Preparation of ibuprofen-loaded liquid suppository using eutectic mixture system with menthol.

Yong CS, Oh YK, Jung SH, Rhee JD, Kim HD, Kim CK, Choi HG.

College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan 712-749, South Korea.

To prepare an ibuprofen-loaded liquid suppository using eutectic mixture with menthol, the effects of menthol and poloxamer 188 (P 188) on the aqueous solubility of ibuprofen were investigated. The physicochemical properties such as gelation temperature, gel strength and bioadhesive force of various formulations composed of ibuprofen, menthol and P 188 were investigated. Then, the pharmacokinetic study of ibuprofen delivered by the liquid suppositories composed of P 188 and menthol were then performed. In the absence of P 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 four parts of ibuprofen formed eutectic mixture with six parts of menthol. In the presence of P 188, the solutions with the same ratio showed abrupt increase in the solubility of ibuprofen. Furthermore, 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 poloxamer gel with menthol/ibuprofen ratio of 1:9 and higher than 15% poloxamer 188 showed the maximum solubility of ibuprofen, 1.2mg/ml. Ibuprofen increased the gelation temperature and weakened the gel strength and bioadhesive force of liquid suppositories. However, menthol did the opposite due to forming the eutectic mixture with ibuprofen. The ibuprofen-loaded liquid suppository [P 188/menthol/ibuprofen (15/0.25/2.5%)] with the maximum ibuprofen solubility of 1.2mg/ml was administered easily to the anus and to remain at the administered site without leakage after the dose. Furthermore, it gave significantly higher initial plasma concentrations, Cmax and AUC of ibuprofen than did solid suppository, indicating that the drug from poloxamer gel could be more absorbed than that from solid one in rats. Thus, the liquid suppository system with P 188 and menthol, a more convenient and effective rectal dosage form for ibuprofen will be expected to enhance the rectal bioavailability of ibuprofen.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15567287&dopt=Abstract ibuprofen Motrin



Motrin
Percutaneous ibuprofen therapy with Trauma-Dolgit gel: bioequivalence studies.

Berner G, Engels B, Vogtle-Junkert U.

Research Laboratories, Dolorgiet, St. Augustin/Bonn, FRG.

The plasma and tissue kinetics of ibuprofen after topical application of 5% Trauma-Dolgit gel were determined in two bioequivalence studies. In eight patients, high ibuprofen concentrations, largely within the therapeutic range, were found in subcutaneous tissue, tendon, muscles and joint capsule. In plasma, however, very low concentrations (decimal exponents below the therapeutically relevant plasma ibuprofen level even after repeated application) were found in nine volunteers. Based upon the comparison of oral and topical ibuprofen forms, the test preparation was found to be bioequivalent and, from a kinetic viewpoint, safe and effective.

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Stereoselective plasma protein binding of ibuprofen enantiomers.

Evans AM, Nation RL, Sansom LN, Bochner F, Somogyi AA.

School of Pharmacy, South Australian Institute of Technology, Adelaide.

We have developed a novel and reproducible method for determining the plasma protein binding of the two ibuprofen enantiomers in the presence of each other. The method involves the use of radiolabelled racemic ibuprofen, equilibrium dialysis, derivatization of the enantiomers to diastereomeric amides, high-performance liquid chromatography, and radiochemical analysis. We have determined the plasma protein binding of R(-)- and S(+)-ibuprofen in 6 healthy male volunteers after the oral administration of 800 mg racemic ibuprofen. The mean time-averaged percentage unbound of the R(-)-enantiomer, 0.419 was significantly less than that of the S(+)-enantiomer, 0.643, consistent with stereoselective plasma protein binding. The percentage unbound of each ibuprofen enantiomer was concentration-dependent over the therapeutic concentration range and was influenced by the presence of its optical antipode.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2744069&dopt=Abstract ibuprofen Motrin



Motrin
Rofecoxib versus ibuprofen for acute treatment of migraine: a randomised placebo controlled trial.

Misra UK, Jose M, Kalita J.

Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India. ukmisra sgpgi.ac.in

BACKGROUND: Rofecoxib is a potent cyclo-oxygenase-2 inhibitor with a long duration of action. Its role in migraine has not been systematically evaluated. AIM: To study the efficacy of rofecoxib in migraine. METHOD: In a randomised placebo controlled trial rofecoxib 25 mg, ibuprofen 400 mg, and placebo were compared regarding their efficacy in relieving acute migraine attack. Migraine patients with 2-6 attacks per month were recruited. Headache severity, functional disability, and severity of associated symptoms were graded on a 0-3 scale. The primary endpoint was pain relief at two hours. Relief of associated symptoms and sustained pain relief for 24 hours were also noted. RESULT: One hundred and twenty four patients were randomised into rofecoxib (42), ibuprofen (40), and placebo (42) groups. One hundred and one patients were followed up: 33 on rofecoxib, 35 ibuprofen, and 33 placebo. Patients' ages ranged from 16-62 (mean 31.4) years, and 83 were females. Pain relief at two hours was noted in 45.5% on rofecoxib, 55.6% on ibuprofen, and 9.1% in the placebo group. The associated symptoms at two hours were reduced in 39.4% on rofecoxib, 50% on ibuprofen, and 9.1% in the placebo group. Sustained 24 hour pain relief was noted in 36.4% on rofecoxib, 41% on ibuprofen, and 6.1% in the placebo group. In the ibuprofen group, five patients had abdominal pain but there were no side effects in those on rofecoxib or in the control group. Both rofecoxib and ibuprofen were significantly effective in relieving pain, associated symptoms at two hours, and in sustained pain relief. There was no significant difference between rofecoxib and ibuprofen in aborting acute migraine attacks. CONCLUSIONS: Both ibuprofen and rofecoxib were superior to placebo in aborting an acute migraine attack, and there was no significant difference in their efficacy in an acute migraine attack.

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Motrin
Dose-dependent pharmacokinetics of ibuprofen in the rat.

Shah A, Jung D.

The linearity of the pharmacokinetics of ibuprofen was examined in male Sprague-Dawley rats given iv bolus doses of 10, 20, and 50 mg/kg ibuprofen. Plasma and urine concentrations of ibuprofen and its two major metabolites, OH-ibuprofen and COOH-ibuprofen, were determined by HPLC and the binding of ibuprofen to plasma proteins was measured by an ultrafiltration technique. The systemic plasma clearance (CLtot) of ibuprofen was dose-dependent and decreased from 0.29 to 0.14 liter/hr/kg primarily as a result of a 65% decrease in the partial metabolic clearance to OH-ibuprofen while the average mean residence time (MRTtot) increased approximately 35% over the 10-50 mg/kg dosage range. Since there were no dose-dependent changes in the apparent steady state volume of distribution (Vss,tot), the mean harmonic half-life increased from 1.7-2.8 hr over the dosage range studied. The binding of ibuprofen to plasma proteins was relatively independent of concentration up to 90 mg/liter (mean free fraction approximately 5.5%), but became markedly concentration-dependent thereafter (free fraction up to 25.4% at 411 mg/liter). The mean recovery of total ibuprofen in the urine over 24 hours at 10 mg/kg was 62.1% and decreased by 24% and 40% at 50 and 20 mg/kg, respectively. This dose-dependent decrease in the percentage excreted in the urine was primarily due to a reduction in the recovery of OH-ibuprofen slightly offset by a small, but significant, increase in the urinary excretion of COOH-ibuprofen between 10 and 50 mg/kg. The apparent pharmacokinetic parameters based on free, unbound concentrations of ibuprofen were also dose-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

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Motrin
Effects of ibuprofen on chemotactic peptide-receptor binding and granulocyte response.

Skubitz KM, Hammerschmidt DE.

Inhibition of complement-mediated granulocyte aggregation has been proposed recently as a mechanism of action of high-dose corticosteroids and ibuprofen in shock states. Such inhibition by corticosteroids may be effected through alteration of receptor function, and we have therefore examined the effect of ibuprofen on the extent and kinetics of binding of the synthetic chemotactic peptide formylmethionine-leucine-phenylalanine (FMLP) to its specific receptor on the granulocyte surface. Dose-dependent inhibition of binding was observed at ibuprofen concentrations paralleling plasma levels achieved with 30 mg/kg intravenous bolus therapy, and also at concentrations achieved with oral therapy. Ibuprofen did not affect the receptor number, but did decrease the association rate constant for the FMLP-receptor interaction (30% of normal for 0.125 mg/ml ibuprofen), leading to a decrease in receptor affinity for ligand. Dissociation kinetics, as determined by cold chase experiments, were unaltered by ibuprofen. We conclude that ibuprofen, like corticosteroids, can slow the rate of association of FMLP with its receptor on the granulocyte surface while allowing dissociation to proceed; altered kinetics of receptor-FMLP interaction may explain the inhibition of granulocyte aggregation. Blockade of granulocyte surface receptors for inflammatory stimuli may be important in the clinical effects of very high-dose corticosteroids and ibuprofen such as are administered in shock; such effects are seen at blood levels of ibuprofen that occur with oral therapy. Similar observations may hold for other physiologic stimuli.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3021168&dopt=Abstract ibuprofen Motrin