Experimental studies on selection of optimal gelling agent and its rational concentration in composition of vaginal gel with essential oils

Abstract

Introduction. The deterioration of the demographic situation is one of the main problems of Ukraine. From 2008 to 2021, the country's population had decreased by 4.5 million, which is associated not only with the economic state of the country, but also with the state of women's health. Reproductive health is significantly affected by infectious diseases of the genital organs of women. One such disease is vaginal candidiasis [3,9].Due to the wide spread of this disease and its tendency to relapse, an important place in the complex of measures for its treatment is given to local intravaginal administration of drugs. In this regard, it is rational to use semisolid dosage forms (SDF), namely vaginal gels, which are able to tightly contact with the vaginal mucosa and quickly release active pharmaceutical ingredients at the site of application [4].The Department of Industrial Technology of Drugs of the National University of Pharmacy is developing the composition and technology of a new gel for the treatment of vaginal candidiasis, which contains essential oils of tea tree, lavender, and lactic acid. Essential oils provide a wide range of antibacterial and antifungal activity. The use of lactic acid allows maintaining a normal pH level of the mucous membranes of the female genital organs, and at the same time, the vital activity of lactobacilli, which suppress the pathogens of most female diseases [5].One of the main issues in the development of the gel is the choice of the gelling agent and its rational concentration. To conduct experimental studies on the selection of the optimal gelling agent in the composition of the vaginal gel, experimental samples have been made with gelling agents approved for medical use: Aristoflex AVC (Ammonium Acryloyldimethyltaurate / VP Copolymer) - France, Clariant, Licigel – Sodium acrylates copolymer (and) Lecithin) – France, Lucas Meyer, Sepimax ZEN (Polyacrylate Crosspolymer-6) - Seppic, France. The purpose of this work was to choose the optimal gelling agent and its concentration in the composition of the developed vaginal gel based on organoleptic, physicochemical, microbiological and structural-mechanical studies.Materials and methods. Using data from scientific literature, gelling agents Aristoflex AVC, Licigel and Sepimax ZEN were used in the composition of the samples at a concentration of 2%.The antimicrobial and antifungal activity of the test samples was studied in vitro by the agar diffusion method (the "wells" method). As test cultures pure cultures were used: gram-positive microorganisms Staphylococcus aureus ATCC 25293, spore culture Bacillus subtilis ATCC 6633, gram-negative cultures Candida tropicalis, Candida glabrata, Candida krusei. During the experiments, one-day suspensions of bacterial microorganisms and two-day suspensions of fungi in physiological saline were used. Microbial overload was 10⁷ microbial cells in 1 mL of nutrient medium [1,2]. The rheological characteristics of the model samples were measured on a rotational viscometer Myr 3000 V2R (Viscotech, Spain) in a system of coaxial cylinders following the SPU method (2.2.10) in a wide range of shear rates. The study was carried out at a temperature of (37 ± 0.1) °C. Based on the measurement results, rheograms of the dependence of the shear (r) on the gradient of the shear rate (Dr) were built. The determination of the homogeneity of the analyzed eyes was carried out according to the methodology induced in DFU 1.0, p.511.Determination of colloidal stability. (GOST 29188.3-91 "Cosmetic products. Methods for determining the stability of emulsions"). The tubes, 2/3 filled with the sample, were placed in a water bath at a temperature of 45 ± 2°C for 20 min, after which they were centrifuged for 5 min at a speed of 6000 rpm. Stability was determined visually, in the presence of stratification - unstable, without changes - stable. Determination of thermal stability. (GOST 29188.3-91 "Cosmetic products. Methods for determining the stability of emulsions"). For determination, 5-6 glass test tubes with a diameter of 15 mm and a height of 150 mm were taken. The test tubes were filled with test samples (8-10) ml and placed in a thermostat brand TS-80M-2 with a temperature of 42.5±2.5 °C for 7 days. After that, the samples were transferred for 7 days to a refrigerator with a temperature of (6±2)°C and then kept at room temperature for 3 days. Stability was determined visually: if no delamination was observed in one tube, the sample was considered stable.Determination of the pH of aqueous gel solutions. The pH level of the studied samples was determined potentiometrically in accordance with the SPU method 2.0, Volume 1, p.2.2.3, p. 51–53. We used the pH-150 МІ device. Results and discussion. The microbiological, structural-mechanical and organoleptic properties of vaginal gel samples with Aristoflex AVC, Licigel and Sepimax™ ZEN gelling agents have been studied. It has been established that the sample with Aristoflex AVC has good sensory properties: soft structure, is quickly and well adsorbed from the mucous membrane without leaving a feeling of stickiness and oily sheen, and also has a non-Newtonian pseudoplastic type of flow. The influence of different concentrations of Aristoflex AVC on rheological properties and microbiological activity has been studied.Conclusions. Based on the results of the experimental studies, Aristoflex AVC gelling agent at a concentration of 1% was chosen as the basis for the gel and the microbiological activity has been studied.

Key words: vaginal gel, gelling agent, organoleptic, microbiological, rheological and physicochemical studies.