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  • Antimicrobial activity of ibuprofen: new perspectives on an "Old" non-antibiotic drug.

Antimicrobial activity of ibuprofen: new perspectives on an "Old" non-antibiotic drug.

European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (2015-02-25)
Jelena Obad, Jagoda Šušković, Blaženka Kos
ABSTRACT

Pharmaceutical industry has been encountering antimicrobial activity of non-antibiotics during suitability tests carried out prior to routine pharmacopoeial microbiological purity analysis of finished dosage forms. These properties are usually ignored or perceived as a nuisance during pharmaceutical analysis. The aim of this study was: (i) to compare the available data to our method suitability test results carried out on products containing ibuprofen, i.e. to demonstrate that method suitability can be a valuable tool in identifying new antimicrobials, (ii) to demonstrate the antimicrobial activity of ibuprofen and ibuprofen lysine. Microbiological purity method suitability testing was carried out according to European Pharmacopoeia (EP), chapters 2.6.12. and 2.6.13. Antimicrobial activity of ibuprofen and ibuprofen lysine was demonstrated by a disk diffusion method, a modification of the European Committee for Antimicrobial Susceptibility Testing method (EUCAST), against test microorganisms recommended in the EP. It was confirmed that ibuprofen may be responsible for the broad spectrum of antimicrobial activity of the tested products, and that method suitability tests according to the EP can indeed be exploited by the scientific community in setting guidelines towards future research of new antimicrobials. In the disk diffusion assay, inhibition zones were obtained with more than 62.5 μg and 250 μg for Staphylococcus aureus, 125 μg and 250 μg for Bacillus subtilis, 31.3 μg and 125 μg for Candidaalbicans, 31.3 μg and 62.5 μg for Aspergillusbrasiliensis, of ibuprofen/disk, and ibuprofen lysine/disk, respectively. For Escherichiacoli, Pseudomonasaeruginosa and Salmonellatyphimurium inhibition zones were not obtained. Antimicrobial activity of ibuprofen is considered merely as a side effect, and it is not mentioned in the patient information leaflets of ibuprofen drugs. As such, for the patient, it could represent an advantage, but, it could also introduce additional risks during usage. Further microbiological, pharmacological and clinical trials are of great importance.

MATERIALS
Product Number
Brand
Product Description

Supelco
Ibuprofen
Ibuprofen, European Pharmacopoeia (EP) Reference Standard
Ibuprofen for peak identification, European Pharmacopoeia (EP) Reference Standard
Supelco
Ibuprofen, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
6-Mercaptohexanoic acid, 90%
Supelco
(±)-Miconazole nitrate salt, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Ethanol solution, certified reference material, 2000 μg/mL in methanol
Sigma-Aldrich
(±)-Miconazole nitrate salt, imidazole antibiotic
Sigma-Aldrich
Ibuprofen, meets USP testing specifications
Sigma-Aldrich
Ibuprofen, ≥98% (GC)
Sigma-Aldrich
Ethanol, anhydrous, denatured
USP
Dehydrated Alcohol, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Ethanol, absolute, denaturated with 0.5-1.5 Vol.% 2-butanone and approx. 0.001% Bitrex (GC), ≥98% (GC)
USP
Ibuprofen, United States Pharmacopeia (USP) Reference Standard
Amoxicillin trihydrate, European Pharmacopoeia (EP) Reference Standard
Supelco
Amoxicillin trihydrate, VETRANAL®, analytical standard
Supelco
Amoxicillin trihydrate, Pharmaceutical Secondary Standard; Certified Reference Material
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Dimethyl sulfoxide, for inorganic trace analysis, ≥99.99995% (metals basis)
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Ethanol, for residue analysis
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Ethanol, purum, secunda spirit, denaturated with 2% 2-butanone, S15, ~96% (based on denaturant-free substance)
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Ethanol, tested according to Ph. Eur.
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Dimethyl sulfoxide, BioUltra, for molecular biology, ≥99.5% (GC)
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Ethanol, standard for GC
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8-Octanoyloxypyrene-1,3,6-trisulfonic acid trisodium salt, suitable for fluorescence, ≥90% (HPCE)
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Ethyl alcohol, Pure, 190 proof, ACS spectrophotometric grade, 95.0%
Supelco
Dimethyl sulfoxide, analytical standard
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Dimethyl sulfoxide, anhydrous, ≥99.9%
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Dimethyl sulfoxide, sterile-filtered, BioPerformance Certified, meets EP, USP testing specifications, suitable for hybridoma
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Dimethyl sulfoxide, meets EP testing specifications, meets USP testing specifications
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Dimethyl sulfoxide, for molecular biology