Justification of preservative choice and its concentration in the composition of anti-allergic action gel

Abstract

Microbiological stability of medicines is an integral part of their quality, therefore, at the stage of pharmaceutical development, the issues of ensuring microbiological purity should be considered. To this end, various chemicals are added to the composition of semisolid medicines that actively inhibit the growth of microorganisms that enter the pharmaceutical system during production and reuse. Insufficient amount of a preservative can lead to the adaptation of microorganisms, and excess- to increase the toxicity of the drug. In the development of the composition of the anti-allergic action gel containing dimethindene maleate and dexpanthenol in order to select a preservative and its concentration, the following antimicrobial substances have been chosen: phenoxyethanol, benzalkonium chloride, methylparahydroxybenzoate (nipagin, E218), propylparahydroxybenzoate (nipasol, E216) and potassium sorbate (E202).
 The purpose of this work is to evaluate the effectiveness of these antimicrobial preservatives in the composition of the gel under study.
 For microbiological studies 5 samples have been developed: N 1 – gel + phenoxyethanol 0.75%; N 2 – gel + benzalkonium chloride 0.015%; N 3 – gel + nipagin 0.15% + nipasol 0.05%; N 4 – gel + potassium sorbate 0.2%; N 5 – gel without preservatives added. The research used the method for evaluating the effectiveness of antimicrobial preservatives given in SPU 2.0 (Section 5.1.3).
 As a result of the experiment, it has been determined that the sample of gel without preservative does not meet the requirements of SPU and proved the need to add antimicrobial preservatives to the composition of the developed gel. The results of the study for samples with preservatives phenoxyethanol 0.75%, benzalkonium chloride 0.015%, nipagin 0.15% + nipasol 0.05% completely meet the requirements of SPU on the indicator «antimicrobial effectiveness of preservatives» for medicinal products for external use. An experimental study of the sample with a potassium sorbate 0.2% preservative showed that it did not fully meet the requirements of the above article of SPU. Among the samples that meet the requirements of SPU, the highest antimicrobial efficacy against strains of Staphylococcus aureus ATCC 6538, Pseudomonas aeruginosa ATCC 9027, Candida albicans ATCC 885-653, Aspergillus brasiliensis ATSC 16404 has shown a sample of 0.75% phenoxyethanol preservative (N 1). Therefore, for further microbiological studies, samples of gels with phenoxyethanol concentrations of 0.5%, 0.75% and 1.0% were prepared and the antimicrobial efficacy of these samples has been studied. Based on experimental studies, it has been found that 0.75% is the optimal concentration of phenoxyethanol in the composition of gel containing dimethidene maleate and dexpanthenol.
 Thus, a complex of studies has been conducted to prove the antimicrobial effectiveness of the phenoxyethanol preservative and its concentration.