INTRODUCTION:

Due to environmental problems, fungal diseases are now widespread. According to WHO statistics, every fifth inhabitant of the planet is affected by this disease. Dermatomycosis is one of the urgent problems of modern medicine. Fungi from the genera Trichophyton and Microsporum are involved in the occurrence of dermatomycosis.

Candida also contributes to the development of fungal diseases, quite often multiplies in places that have been subjected to mechanical stress, for example, near open wounds. Therefore, the need for the development of modern antifungal medicines is urgent. Despite the effectiveness of existing antimycotic drugs, some of them exhibit undesirable or side effects, as the widespread use of pharmaceutical preparations based on chemical advances has led to new problems, in particular to sensitization and allergization of the body, disruption of homeostasis due to the toxic effects of chemicals. These disadvantages are mainly deprived of preparations based on medicinal plants, which are natural to humans and in certain quantities stimulate the physiological reactions of the body, contributing to their normalization in case of painful disorders. Therefore, we considered it expedient to create and introduce into the practice of dermatotherapy herbal medicines that are safer, polyvalent and suitable for long-term use. Technological, biopharmaceutical, and microbiological methods were used. The result of this study was the construction of an antifungal gel with proven microbiological activity.

There is a growing interest in herbal medicines, which often contain a balanced composition of biologically active substances (BAS) that do not cause toxic, allergic, or irritating reactions, and at the same time have high therapeutic activity in various diseases ^1,2. Unlike synthetic drugs, the use of herbal preparations does not cause side effects, including the appearance of resistant strains of microorganisms, which is especially important in the long-term treatment of wounds accompanied by inflammatory processes^3-5.

A rational combination of essential oil with various auxiliary substances, the development of a mild dosage form for external and topical use, can expand the therapeutic possibilities of medicines for the treatment and prevention of many diseases ^6-8.

Essential oil from vegetable raw materials of Ferula songarica, obtained by hydrodistillation, has shown high effectiveness against microorganisms, which contributes to the promising use of this pharmaceutical substance in the creation of a gel with bactericidal properties ^16-19. Possessing wide range of medicinal properties, a perennial plant of the umbrella family, Ferula songarica was one of the most popular medicines of avestan medicine back in the 8th-6th centuries BC. Ancient healers mainly used ferula roots for medicinal purposes, as well as gum resin "asafoetida" extracted from its roots. Ferula songarica is a perennial herbaceous plant of the umbelliferaceae family with a stem reaching 4 meters in height. The leaves are triple-dissected, mostly basal, collected in a rosette. Small, less than a centimeter in diameter, the flowers of light shades of yellow are collected in large paniculate inflorescences. The fruit of the Ferula songarica is flat, compressed oval in shape. This plant blooms in the second half of spring, matures in the last days of the same period. Ferula songarica is traditionally considered to be native to Iran, India and Afghanistan, and is also widespread in Kazakhstan, China, Mongolia and the Russian Federation. It grows most often on rocky mountain slopes and in thickets of steppe shrubs ^9-12.

MATERIALS AND METHODS:

As plant raw materials, we used the underground part of Ferula songarica, collected in the vicinity of Karkaralinsk (49°24'21" north and 75°28'27" east) of the Karaganda region.

Essential oils were isolated by hydrodistillation at a Clevenger laboratory facility ¹³. 15-20 grams of raw materials were placed in a flask, 300 ml of water was poured, the flask was connected through a slot to a steam-conducting tube and a graduated tube was filled with water through a tap using a hose with a funnel. The contents of the flask were heated to a rapid boil and boiled at an intensity at which the rate of distillate runoff should be 60-65 drops per 1 minute for 2 hours. 5 minutes after the end of distillation, the volume of essential oil was measured. To do this, a tap was opened and part of the distillate was lowered to the level of the graduated tube divisions. The percentage was determined by the volumetric method.

To study the qualitative and quantitative composition of Ferula songarica essential oil and essential oil-based gel, the chromatography-mass spectrometry method was used using an Agilent Technologies 7890 A gas chromatograph with an MSD 5975 C quadrupole mass spectrometer as a detector. The HP-5MS capillary column measured 30 m x 0.25 mm (film thickness 0.25 microns). The evaporator temperature is 230 0C. The gas chromatographic column was kept at a temperature of 40 ° C for 10 minutes; with temperature programming up to 240 ° C at a temperature change rate of 2 ° C/min, and then kept in isothermal mode for 20 minutes. The sample input mode is 100:1 flow division. The sample volume is 0.2 µl. The recording conditions of the mass spectra are 70 eV, the mass range is m/z 10-360. The MSD ChemStation software supplied by Agilent Technologies was used for data processing in combination with AMDIS 32 and NIST 2020 ^14-18.

Study of antifungal activity by diffusion into agar

The antifungal activity was studied against the yeast fungi Candida albicans, Candida glabrata and Candida dubliniensis by diffusion on agar discs soaked in a solution of the test substance. The cultures were grown in a liquid medium with a pH of 7.3 ± 0.2 at a temperature of 25±1ºС for 18-24 hours. The cultures were diluted 10⁵ CFU/ml in a sterile 0.9% isotonic sodium chloride solution, 1 ml each was added to cups with appropriate elective, nutrient media for the test strains under study and seeded using the "continuous lawn" method. After drying, 6.0 mm wells were formed on the surface of the agar, into which solutions of the studied samples and nystatin were added. 70% ethyl alcohol in equivalent quantities was used as a control. The crops were incubated at 37⁰C, and the growing crops were recorded after 24 hours.

The antifungal activity of the Ferula songarica essential oil sample was assessed by the diameter of the growth retardation zones of the test strains (mm). Each sample was tested in three parallel experiments. Statistical processing was carried out using parametric statistics methods with calculation of the arithmetic mean and standard error ^19-25.

RESULTS AND DISCUSSION:

The component composition of the essential oil of the underground part of Ferula songarica and the gel based on the essential oil of Ferula songarica has been studied. The oil sample is a yellow mobile liquid with a characteristic odor, 113 components were detected in the underground part – α-pinene - 32.91% and 3-octene-5-in, 2,7-dimethyl-, (E)- 19.47% (Table 1).

Table 1 – The main components of the essential oil of the underground part of Ferula songarica

The hold index	Component	Content, (%) in EMF	Content, (%) in EMF gel
937	α- pinene	32.91	29.28
912	3-Octen-5-yne, 2,7-dimethyl-, (E)-	19.47	13.14
991	Β- Myrcene	12.98	1.13
1003	3-Carene	6.01	0.03
1060	γ- Terpinene	2.49	0.08
1348	Copaene	1.49	1.16
1428	(-)-Aristolene	6.45	1.89
1439	1,1,7,7a-Tetramethyl-1a,2,6,7,7a,7b-hexahydro-1H-cyclopropa[a]naphthalene	1.49	0.56
1423	1H-Cyclopropa[a]naphthalene, 1a,2,3,5,6,7,7a,7b-octahydro-1,1,7,7a-tetramethyl-, [1aR-(1a.α.7α.7a.α..,7b.α.)]-	3.34	0.55
1441	(-)-1,2,2.α.,3,3,4,6,7,8,8. α.-decahydro-2. α.,7,8-trimethylacenaphthylene	2.5094	1.57
1468	(E)-β.- Famesene	3.65	2.86

Choosing the gel composition:

On the basis of the NPJSC "Karaganda Medical University", research has been conducted on the pharmaceutical development of a gel with essential oil obtained by hydrodistillation. The model concentration was 3%, which corresponded to the therapeutic properties of the essential oil, proven experimentally. The pharmacological activity of gels largely depends on the correct choice of the gel base, since it determines the rate and completeness of the release of the active drug from the gel. The selection of suitable bases for gel formation is a significant task, since it was necessary to use both lipophilic and hydrophilic bases that do not cause allergic reactions, irritation and ensure the effective release of the medicinal substance from the gel. Preliminary studies have been conducted on the selection of gelling agents and the assessment of the physico-chemical and structural-mechanical properties of the bases used.

As a result, 5 compositions of a mild dosage form using sodium carboxymethylcellulose (Na-CMC) were selected for further research. The quantitative content of all excipients was selected based on a literature review, as well as empirically.

All selected bases met the requirements of the State Pharmacopoeia of the Republic of Kazakhstan and the Pharmacopoeia of the Eurasian Economic Union for the basics of gel preparation.

Substantiation of the composition and development of technology for a gel dosage form based on Na-CMC.:

Sodium carboxymethylcellulose (Na-CMC) is a water-soluble polymer, a derivative of cellulose, which is used in various pharmaceutical and cosmetic forms due to its remarkable properties: the formation of viscous solutions and gels, good biocompatibility and ability to retain moisture. Na-CMC is used in pharmaceuticals to create gel dosage forms for topical use, such as gels, ointments, creams, and eye drops. It helps to improve the texture, stability and durability of drugs.

Sodium carboxymethylcellulose (Na-CMC) is added to medicinal gels for several reasons, including:

Thickener: Na-CMC has the properties of a thickener, which allows you to adjust the consistency of the gel. This makes it more convenient to apply to the skin and helps to keep the drug in place for a longer time.

Stabilizer: Na-CMC stabilizes the shape and structure of the gel, preventing its delamination and precipitation of active ingredients, which improves the shelf life and effectiveness of the drug.

Improved adhesion: Due to its properties, Na-CMC promotes better adhesion of the gel to the skin, providing a more effective and long-lasting effect of active substances.

Hydrophilic properties: Na-CMC has a high water retention capacity, which helps maintain an optimal moisture level in the preparation and improves its lubricating and moisturizing characteristics.

Control of the release of active substances: In some cases, Na-CMC can be used to control the rate of release of active substances from the gel, which is important for the prolonged effect of the drug.

Safety and Compatibility: Na-CMC is a safe and well-tolerated component, making it suitable for use in pharmaceutical and cosmetic products.

The process of developing a gel dosage form includes several key steps:

The dissolution of Na-CMC: The water is heated to a temperature of about 40-50° C and Na-CMC is added, stirring thoroughly to prevent the formation of lumps. The dissolution process should be slow and gradual to achieve a homogeneous mass.

pH regulation: After Na-CMC is completely dissolved, the neutralizing agent NaOH is added to achieve an optimal pH (6-8). This is a necessary step for Na-CMC to form the desired viscosity and texture.

Addition of active substances: After the gel is formed, the active substance essential oil is added. The essential oil is evenly distributed over the entire gel mass to ensure effective local action.

Conservation: To prevent the growth of microorganisms, the preservative benzyl alcohol is added to the gel.

The addition of sodium carboxymethyl cellulose (Na-CMC) to medicinal gels helps to achieve several key goals: Providing the desired texture: Na-CMC improves the consistency of the gel, which makes it convenient to apply and helps to keep the drug on the skin. Increased effectiveness and duration of action: Due to the ability of Na-CMC to improve adhesion and control the release of active substances, it contributes to a longer and more effective effect of the drug. Formula stability: Na-CMC helps to stabilize the shape of the gel, preventing delamination and precipitation of components, which increases shelf life and preserves the effectiveness of the drug.

No. 1. When the gel was ready, it turned into a homogeneous mass of whitish color, with a characteristic garlic smell.

Np. 2. When the gel was ready, it had a light color, a characteristic garlic smell, the consistency was thicker, sticky, and deficiencies in organoleptic properties were noted.

No. 3. When the gel was ready, it had a white color, a characteristic garlic smell, the consistency was thicker, it was noticed that it was poorly applied to the skin.

No. 4. When the gel was ready, it turned out to be white, with a characteristic garlic smell, its consistency resembled a scrub, and insufficient organoleptic properties were noticed.

No. 5. When the gel was ready, it became white, transparent, with a characteristic odor and turned into a homogeneous mass.

Determination of thermal stability of selected formulations.

To determine the thermal stability, 10.0 g of gel was placed in a tube with a tight stopper so that the gel layer was as dense and homogeneous as possible. Next, one series of tubes was kept for 24 hours in a thermostat at 37° C, the other in a freezer at -18 ° C, and then thawed. According to the results of thermal stability tests, composition № 4 is stable both after thermostating at 37 ° C and after freezing at -20 °C.

The study of the release of α-pinene from gels by the method of "direct diffusion into agar".

The study of the release of the active substance from the gel was carried out by the method of "direct diffusion into agar" in a thermostat for 3 hours. Methylene blue was used as the coloring ingredient, since α-pinene, when released, colors the agar in a dark blue color. A 2% agar solution was prepared, poured into Petri dishes, cooled for an hour, then wells with a diameter of 8.5 mm were cut out and gels based on Ferula songarica essential oil with different base compositions weighing 0.25 g each were placed in them. The studies were conducted in 3 parallels at a temperature of 36.6 ± 0.2 ° C. The degree of diffusion into the agar was assessed visually by changing the color of the zones to dark blue. The results are shown in Figure 1.

Figure 1: Kinetics of Ferula songarica essential oil release from gel compositions by diffusion into agar (model 4)

Thus, the intensity of release is influenced by certain factors, such as the nature of the base and the methods of preparation of the dosage form. According to experimental studies, model No. 4 has the best performance in terms of the kinetics of the release of the active substance α-pinene by "direct diffusion into agar".

Thus, sample № 4 was adopted as the optimal gel composition. As a result of complex phytochemical and technological studies, the gel composition was substantiated and proposed: Ferula songarica essential oil, obtained by hydrodistillation – 3.0; Na-CMC – 15.0; glycerin – 3.5; sodium hydroxide – 0.5; twin 80-1,2; benzyl alcohol - 0.3; purified water – up to 100.

Rheological properties of Ferula songarica Essential Oil Gel:

Rheological properties allow us to judge the fluidity of the gel, the ability to be easily distributed over the skin, the release of active substances, therapeutic efficacy, as well as the stability of the drug during storage. The studies were carried out by the method of continuous, sequential destruction of the structure during the transition from small to large shear rate gradients and from large to small at a temperature of (20 ± 2) ° C, using a Brookfield NDJ-1F rotary viscometer [20-21]. To study the thixotropic properties of an essential oil-based gel, curves of the tangential stress dependence on the shear flow velocity gradient were constructed (Figure 2).

Figure 2: Rheogram of deformation kinetics based on Ferula songarica essential oil (model No. 4)

As can be seen from Figure 2, the flow of the system does not occur immediately; at low shear rates, the system has the highest viscosity, and the gel structure has time to fully recover after minor destruction. As the shear rate increases, the structure begins to deform, and the gel begins to flow. During the period of gradual weakening of the viscosity stress, the structure of the ointment begins to recover, but its recovery is somewhat delayed. The presence of an "ascending" curve characterizing the destruction of the system and a "descending" curve characterizing the restoration of the system forming a "hysteresis loop" indicates the thixotropy of the gel under study. The area of the "hysteresis loop" allows us to judge the mechanical stability of structured systems: the smaller it is, the more mechanically stable the system is.

Definition of antifungal action:

Samples were examined to determine the optimal composition of the gel, which provides a therapeutic effect. The results were evaluated by the diameter of the growth inhibition zones of pathogenic microorganisms (Table 3).

Table 3. Antifungal activity of the studied samples against yeast fungi (the inhibition zone is measured in mm)

mm *Code sample*	Candida albicans 62608	Candida glabrata 62706	Candida dublniensis 62610
Essential oil	41±0.71	39±0.71	42±0.41
№4 gel	30±1.08	24±1.22	28±1.41
Nystatin	25±0.71	23±0.71	23±0.71
Ethyl alcohol (70%)	9±0.41	8,5± 0.41	9± 0.71

Note: The antifungal activity of the samples was assessed by the diameter of the growth retardation zones of the test strains (mm). The diameter of the growth retardation zones is less than 10 mm. Continuous growth in the cup was assessed as the absence of antibacterial activity, 10-15 mm- weak activity, 15-20 mm- moderate activity, over 20mm-pronounced.

Microbiological studies have shown that gel No. 4 with Ferula songarica essential oil based on HCMC exhibits pronounced antifungal activity against the yeast fungi Candida albicans, Candida glabrata and Candida glabrata.

Thus, the study of the composition and fungicidal properties of a gel based on Ferula songarica essential oil made it possible to determine the constituent components of a new domestic antifungal drug.

The conducted research demonstrated the prospects of using Ferula soongarica essential oil, which grows in Central Kazakhstan, in the development of an antifungal agent.

The composition of the gel based on the sodium salt of carboxymethylcellulose (CMC) has been developed, which ensures optimal rheological characteristics and stability of the dosage form. The tests carried out have confirmed the high effectiveness of the gel based on Ferula soongarica essential oil, which makes it possible to recommend the proposed gel as an antifungal agent.

The results obtained open up new opportunities for using the natural resources of the region in the creation of effective and environmentally friendly drugs.

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Received on 18.02.2025 Revised on 12.06.2025

Accepted on 16.08.2025 Published on 13.01.2026

Available online from January 17, 2026

Research J. Pharmacy and Technology. 2026;19(1):131-136.

DOI: 10.52711/0974-360X.2026.00020

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.

Name of ingredients	Appointment	Samples
Name of ingredients	Appointment	FS1	FS2	FS 3	FS 4	FS 5
Essential oil(g)	Active substance	3	3	3	3	3
Na-CMC (g)	Gel base	15	15	15	15	15
Glycerin (ml)	Plasticizer	1	1,5	2	3,5	3
NaOH hydroxide 10%	Acidity regulator	2,5	1,5	2	0,5	1
Twin 80 (ml)	Stabilizer	1	3	1,5	1,2	1,8
Benzyl alcohol	Preservative	0,3	0,3	0,3	0,3	0,3
purified water (ml)	Solvent up to	100	100	100	100	100