Department of Analytical Laboratories, Research and Development Department, Belupo Inc., Danica 5, HR-48000 Koprivnica, Croatia.
Laboratory for Antibiotic, Enzyme, Probiotic and Starter Culture Technology, Department of Biochemical Engineering, Faculty of Food Technology and Biotechnology, University of Zagreb, Pierottijeva 6, HR-10000 Zagreb, Croatia.
Eur J Pharm Sci. 2015 Apr 25;71:93-8. doi: 10.1016/j.ejps.2015.02.011. Epub 2015 Feb 20.
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.
制药行业在对成品剂型进行常规药典微生物纯度分析之前的适用性测试中，已经遇到了非抗生素的抗菌活性。这些特性在药物分析过程中通常被忽视或视为一种麻烦。本研究的目的是：（i）将可用数据与我们在含有布洛芬的产品上进行的方法适用性测试结果进行比较，即证明方法适用性可以成为识别新抗菌剂的有用工具，（ii）证明布洛芬和布洛芬赖氨酸的抗菌活性。根据欧洲药典（EP）第 2.6.12 章和 2.6.13 章进行微生物纯度方法适用性测试。通过欧洲抗菌药物敏感性测试委员会（EUCAST）方法的修改版，即圆盘扩散法，对布洛芬和布洛芬赖氨酸的抗菌活性进行了测试，针对 EP 中推荐的测试微生物。结果证实，布洛芬可能是测试产品广谱抗菌活性的原因，并且 EP 中的方法适用性测试确实可以被科学界利用，为未来新抗菌剂的研究制定指导方针。在圆盘扩散试验中，布洛芬/圆盘和布洛芬赖氨酸/圆盘分别获得了对金黄色葡萄球菌的超过 62.5μg 和 250μg、对枯草芽孢杆菌的 125μg 和 250μg、对白色念珠菌的 31.3μg 和 125μg、对巴西曲霉的 31.3μg 和 62.5μg 的抑制带。对于大肠杆菌、铜绿假单胞菌和鼠伤寒沙门氏菌，未获得抑制带。布洛芬的抗菌活性被认为仅仅是一种副作用，在布洛芬药物的患者信息传单中并未提及。因此，对于患者来说，这可能是一个优势，但在使用过程中也可能带来额外的风险。进一步的微生物学、药理学和临床试验非常重要。
