Study of the efficacy of antimicrobial preservatives in justifying the composition of a dermatological gel with a phytocomplex
Keywords:phytocomplex gel, effect, preservatives, Euxyl 9010K (90 % phenoxyethanol, 10 % ethylhexylglycerol), methyl parahydroxybenzoate (E218), sorbic acid, potassium sorbate, benzoic acid
The microbiological stability of medicinal products always requires close attention during the pharmaceutical development phase, as microbial contamination can pose a threat to both the health of the patient and the stability of the medicinal product. The level of microbial contamination can be controlled by monitoring the quality of raw materials, compliance with appropriate sanitation of production facilities and equipment, the use of scientifically justified preservatives in the drug.
The aim of the work is to substantiate the use of a preservative and its concentration in the composition of the developed gel with phytocomplex.
Materials and methods. The objects of the study were gel samples with the addition of a preservative: Euxyl 9010K (90 % phenoxyethanol, 10 % ethylhexylglycerol), methyl parahydroxybenzoate (E218), sorbic acid, potassium sorbate, benzoic acid. Concentrations of antimicrobial substances used corresponded to their average value from the range of used concentrations. The research has used the method of evaluating the effectiveness of antimicrobial preservatives, given in SPU 2.0.
Results. Experimental studies using preservatives Euxyl 9010K 0.60 %, methyl parahydroxybenzoate 0.25 %, sorbic acid 0.10 %, potassium sorbate 0.25 %, benzoic acid 0.15 % in the samples of the developed gel with phytocomplex had shown that the obtained results for all samples fully meet the requirements of SPU in terms of “antimicrobial efficacy of preservatives” for topical drugs. According to the results of the first stage of research, it had been found that the greatest antimicrobial efficacy was shown by a sample with the preservative Euxyl 9010K. The subject of the second stage of research was the substantiation of the concentration of Euxyl 9010K (0.45 %, 0.60 %, and 0.75 %) based on the results of which it had been established that the gel samples with concentrations of Euxyl 9010K 0.60 % and 0.75 % met the requirements of SPU on the indicator of “antimicrobial efficacy of preservatives” for topical medicinal products. The sample with a concentration of Euxyl 9010K 0.45 % also met these requirements, but the logarithm of the reduction in the number of viable cells of Pseudomonas aeruginosa bacteria after 2 days of storage is 2.00, which was the limit value according to the requirements of SPU.
Conclusions. The expediency of using Euxyl 9010K (90 % phenoxyethanol, 10 % ethylhexylglycerol) at a concentration of 0.60 % as a preservative had been experimentally substantiated.
Derzhavnyi reiestr likarskykh zasobiv Ukrainy [State Register of Medicines of Ukraine]. http://www.drlz.kiev.ua/
Normatyvno-dyrektyvni dokumenty MOZ Ukrainy [Regulatory documents of the Ministry of Health of Ukraine]. http://mozdocs.kiev.ua/liki.php/
Popova, T. V., Strilets, O. P., & Kukhtenko, H. P. (2020). Obgruntuvannia vyboru konservanta ta yoho kontsentratsii u skladi heliu protyalerhichnoi dii [Justification of preservative choice and its concentration in the composition of anti-allergic action gel]. Farmatsevtychnyi Zhurnal, 75(4), 78-87. [in Ukrainian]. https://doi.org/10.32352/0367-3057.4.20.08
Pastor-Nieto, M. A., Alcántara-Nicolás, F., Melgar-Molero, V., Pérez-Mesonero, R., Vergara-Sánchez, A., Martín-Fuentes, A., González-Muñoz, P., & de Eusebio-Murillo, E. (2017). Preservatives in Personal Hygiene and Cosmetic Products, Topical Medications, and Household Cleaners in Spain. Conservantes en productos de higiene y cosméticos, medicamentos tópicos y productos de limpieza doméstica en España. Actas dermo-sifiliograficas, 108(8), 758-770. https://doi.org/10.1016/j.ad.2017.04.003
Nowak, K., Jabłońska, E., & Ratajczak-Wrona, W. (2021). Controversy around parabens: Alternative strategies for preservative use in cosmetics and personal care products. Environmental research, 198, 110488. https://doi.org/10.1016/j.envres.2020.110488
Ministry of Health of Ukraine. (2020). ST-N MOZU 42-3.4:2020 Likarski zasoby. Nastanova z vyrobnytstva hotovykh likarskykh zasobiv [ST-N MOH 42-3.4:2020 Drugs. Guideline on manufacture of the finished dosage form]. [in Ukrainian]. https://zakon.rada.gov.ua/rada/show/v1077282-20#Text
Ministry of Health of Ukraine. (2020). ST-N MOZU 42-4.0:2020 Likarski zasoby. Nalezhna vyrobnycha praktyka [ST-N MOH 42-4.0:2020 Drugs. Good manufacturing practice]. [in Ukrainian]. https://zakon.rada.gov.ua/rada/show/v1023282-20?lang=en#Text
Ministry of Health of Ukraine. (2020). ST-N MOZU 42-4.2:2011 Likarski zasoby. Upravlinnia ryzykamy dlia yakosti (ICH Q9) [ST-N MOHU 42-4.2:2011 Medicinal Products. Quality Risk Management (ICH Q9)]. https://compendium.com.ua/uk/clinical-guidelines-uk/standartizatsiya-farmatsevtichnoyi-produktsiyi-tom-1/st-n-mozu-42-4-2-2011/ [in Ukrainian].
Ministry of Health of Ukraine. (2011). ST-N MOZU 42-3.0:2011 Likarski zasoby. Farmatsevtychna rozrobka (ICH Q8) [ST-N MOHU 42-3.0:2011 Medicinal Products. Pharmaceutical Development (ICH Q8)]. [in Ukrainian]. https://compendium.com.ua/uk/clinical-guidelines-uk/standartizatsiya-farmatsevtichnoyi-produktsiyi-tom-1/st-n-mozu-42-3-0-2011/
Sheskey, P. J., Cook, W. G., & Cable, C. G. (Eds.). (2017). Handbook of Pharmaceutical Excipients (8th ed.). American Pharmacists Association, Pharmaceutical Press.
Regulation (EC) No 1223/2009. European parliament and of the council of 30 November 2009 on cosmetic products (2009). Official Journal of the European Union, L 342/59-L 342/209. Available at: https://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2009:342:0059:0209:en:PDF
State Enterprise Ukrainian Scientific Pharmacopoeial Center of Medicines Quality. (2014). Derzhavna Farmakopeia Ukrainy [The State Pharmacopoeia of Ukraine] (2nd ed., Vol. 1). Kharkiv: State Enterprise Ukrainian Scientific Pharmacopoeial Center of Medicines Quality. [in Ukrainian].
Dréno, B., Zuberbier, T., Gelmetti, C., Gontijo, G., & Marinovich, M. (2019). Safety review of phenoxyethanol when used as a preservative in cosmetics. The Journal of the European Academy of Dermatology and Venereology, 33(S7), 15-24. https://doi.org/10.1111/jdv.15944
Scientific Committee on Consumer Safety (SCCS) & Lilienblum, W. (2016). Opinion of the Scientific Committee on Consumer Safety (SCCS) - Final version of the opinion on Phenoxyethanol in cosmetic products. Regulatory toxicology and pharmacology : RTP, 82, 156. https://doi.org/10.1016/j.yrtph.2016.11.007
How to Cite
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)