Experimental justification of the choice of antimicrobial preservative in the combined gel

Abstract

Introduction. The presence of microorganisms in non-sterile drugs could cause a reduction or even inactivation of their therapeutic effect, so at the stage of pharmaceutical development it should be considered to ensure the stability of drugs. Materials and methods. Tests of the effectiveness of antimicrobial preservatives were performed according to the method of SPhU 2.3, article 5.1.3.

Materials: nutrient media: soy-casein agar, Saburo-dextrose agar; solutions - buffer solution with sodium chloride and peptone pH = 7.0, which contains 50 g/l of polysorbate-80, 5 g/l of lecithin, 1 g/l of histidine hydrochloride. The sterility of nutrient media, solvent and growth properties of nutrient media were tested. Test cultures of microorganisms: St. aureus ATCC 6538, Ps. aeruginosa ATCC 9027, C. albicans ATCC 10231, As. brasiliensis ATCC 16404. Preparation of the inoculum was carried out according to SPhU 2.3, item 5.1.3.  Results and discussion. According to the research, a sample of gel without preservative (№ 1) undergoes microbiological testing only for bacteria St. aureus, which confirms the literature on the moderate antimicrobial action of the active components of the gel, in particular quercetin, on gram-positive bacteria. But it does not meet the requirements of SPhU, because the logarithm of the reduction of the number of viable microorganisms Ps. aeruginosa less than 2.0 and 3.0 after 2 days and 7 days, respectively. For cells of fungi C. albicans and As. brasiliensis on the 14th day Lg reduction of the number of viable cells in the samples according to the requirements of SPhU should be at least 2.0, and in the sample without preservatives observed 1.76 and 1.65, respectively, which also does not meet the requirements. The obtained results prove the need to add antimicrobial preservatives to the composition of the developed gel. Given the requirements of safety and economy when using preservatives, as well as the main properties of butyloxyanisole as a fat-soluble antioxidant to create oxystable compositions, the most acceptable preservative in creating a gel with vegetable oils is butyloxyanisole in the least effective of the studied concentrations - 0.03%. Samples of the gel with the preservative in the selected concentration were stored for quality studies. 

Key words: combined gel, antimicrobial preservatives, stonecrop juice, fatty oils, stability.

DOI: 10.5281/zenodo.6350007