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Section 2. Medical science
https://doi.org/10.29013/ESR-21-9.10-7-11
Chubinidze Natia Zaurievna, PhD Student, Akaki Tsereteli State University, Kutaisi, Georgia
E-mail: [email protected] Bashura Aleksandr Gennadievich, Doctor of Pharmaceutical Sciences, Professor, National University of Pharmacy, Kharkiv, Ukraine E-mail: [email protected] Abuladze Nino Bejhanovna, PhD in Pharmacy, professor, Akaki Tsereteli State University, Kutaisi, Georgia E-mail: [email protected] Gabunia Ketevani Ushangovna, PhD in Pharmacy, Associate Professor, Akaki Tsereteli State University, Kutaisi, Georgia E-mail: [email protected] Sulashvil Nodar Vakhtangevich, MD, PhD, Doctor by Theoretical Medicine in Pharmaceutical and Pharmacological Sciences, Associate Professor of Tbilisi Open University, International School of Medicine, Division of Pharmacology, Tbilisi, Georgia
E-mail: [email protected]
DEVELOPING THE FORMULATIONS OF THE COMPOSITIONS FOR ACNE SPOT TREATMENT
Abstract: Acne vulgaris is a chronic recurrent disease of the sebaceous-follicular apparatus with localization in the areas of face, back, chest, and sometimes buttocks. The literature indicates that great numbers of the world's population aged between 18 and 25 years suffer from this disease. Persons of all races and members of either gender are affected by this disease. Disease does not directly threaten the life, but it can significantly impede the patient's social adaptation and requires both treatment and psychological assistance. The treatment has to be started at an early stage of the disease, and besides, without affecting the regions of skin that do not contain the acne elements.
The purpose of this study was to develop cosmeceuticals for acne spot treatment in the form of creams and solutions, using biologically active substances mostly of natural origin.
The compositions of creams and solutions have been developed in several versions for acne spot treatment, the biologically active part of which consists of substances mainly of plant and natural origin. All the developed versions are not allergic and show a sufficiently high medicinal activity.
Keywords: Acne vulgaris, kerato-regulating effect, Tea tree, bioavailability.
Introduction
Acne vulgaris is one of the most widespread chronic recurrent diseases of the sebaceous-follic-ular apparatus with localization in the areas of face, back, chest, and sometimes buttocks. The literature indicates that great numbers of the world's population aged between 18 and 25 years suffer from this disease [1-3]. Persons of all races and members of either gender are affected by this disease. Disease does not directly threaten the life, but it can significantly impede the patient's social adaptation and requires both treatment and psychological assistance. One of the difficulties in treatment is that it is impossible to ensure the absence of aggravations, since predisposition to acne disease is coded genetically, and even if the steady remission is achieved, the recurrence of certain causes (predisposing factor) can lead to the development of disease. It is advisable to control the process in a timely manner, excluding the possibility of aggravation, often resulting in cosmetic defects that significantly impede the patient's social adaptation. The earliest changes with acne consist in pathological hyperkeratinization of the follicular epithelium and the microcomedone-forming follicular canal obturation. Later it develops to a clinically visible closed ("white head") or open ("black head") comedone. Changes in the epidermis and dermis in inflammatory forms of acne are associated with irregular acanthosis, hyper- and parakeratosis, polymorphic cell perifollicular infiltration, pronounced by disorganization of connective tissue. After clinical resolution of inflammatory elements in the dermis, changes remain the same in the form of hairy-glandular or piloseba-ceous units "clamped" in connective tissue, foci of granulomatous inflammation, and the formation of
cystic cavities, which may be a source of the recurrence of the inflammatory process in the future. It is all related to the appropriateness of including anti-inflammatory, absorbing and regeneration-stimulating agents in therapy. Overproduction of sebum plays a complementary role in the pathogenesis ofacne. The increase in sebum production usually correlates with the disease severity, as this reduces the concentration of linolenic acid, which is a predisposing factor for follicular hyperkeratosis; moreover, the sebaceous matter is also a substrate for the reproduction of Propionibacterium acnes (P. acnes).
The American Academy of Dermatology defines the initial 1st and 2nd degrees of the acne severity, as 1st degree - comedones (open and closed), up to 10 papules; and 2nd degree - comedones, papules, up to 5 pustules.
Usually, it is recommended to apply methodology that includes at some stage the use of a topical method of treatment - peeling (with ascorbic acid, alpha and beta hydroxyl acids), as well as the use of drugs that reduce sebaceous activity (for example, drugs containing vitamin A), elimination of the bacterial background, in particular gram-negative Propionibacterium acnes, Staphylococcus epidermidis, Staphylococcus aureus, which may be involved in the development of the inflammatory response [4].
For daily facial cleansing treatment, it is recommended to use gels with kerato-, sebo-regulating and anti-inflammatory effects. For example, the preparations containing thermal waters: Effaclar lines (La Roche-Posay) and Clearance curative cosmetics lines (Avene), as well as Merck Exfoliac, Sebium Bio-derma and so on. One of the options for topical acne treatment is antibiotic therapy. However, there are
not uncommon the cases of P. acnes non-response, with temporary side effects such as diarrhea, gastrointestinal upsets, and a high risk of pseudomembranous colitis. Benzoyl peroxide has a pronounced antibacterial effect, but it can cause significant dry-ness of the skin, and the contact irritable dermatitis. Retinoids are also similarly characterized by side effects. Consequently, in recent years, more frequent use has been made of the preparations in the form of cosmeceuticals [5-9], which contributes to a gentler and more effective treatment. Medical and cosmetic products should be non-comedogenic, and they should not cause dryness and irritation. The drugs used in patients with acne should actively adsorb sebum without disturbing the balance of lipids and ceramides, the water-lipid mantle; they should effectively moisturize the skin due to the substances used in the compositions of the bases of creams, and have a kerato-regulating effect. For example, Avene Clearance K Cream-gel contains 0.1% salicylic acid - Beta hydroxy acid and 2% lactic acid, which enhance the kerato-regulating action of glycolic acid; Topicrem AK Emulsion Active has sebum-regulating (zinc gluconate 1%), keratolytic (lactic acid ester 10%), and antibacterial (myristyl PCA 1%) effects. TOPICREM AC Compensating Moisturizing Cream contains glycerin, beeswax, allantoin and so on.
To date, there are widely used the agents applied point-by-point to the problematic skin areas, contributing to their early recovery, as it helps to fight off bacteria that cause acne - Ciracle Anti-Blemish Spot-X, Ciracle Anti-Blemish Spot-X Cream. They also soothe the skin, reduce the secretion of sebum, prevent the emergence of the skin tightness and post-acne scars, and eliminate skin redness. The most widely used in the composition are: tea tree oil - an antiseptic that has antifungal, antiviral, anti-inflammatory, bactericidal, and wound-healing effect, capable of removing the pus from the inflamed micro-areas; lactic acid, that regulates the functioning of sebaceous glands, preventing the acne manifestations, and has antimicrobial and anti-inflammatory
effect and moisturizes the skin; glycolic acid accelerates skin cell renewal, removes dead skin particles and can increase the content of hyaluronic acid in the skin; salicylic acid, which has an anti-inflammatory, exfoliating and keratolytic effect, and has a strongest antibacterial effect, is effective in treating acne, dissolves sebum in pores, and accelerates skin regeneration. The therapeutic effect of mandelic acid is weaker than that of glycolic acid, but the irritating effect is also less pronounced. In addition, its bactericidal effect makes it advisable to use mandelic acid as part of combined peelings for the treatment of acne. Chlorhexidine is a medicinal substance, the antiseptic, in the finished dosage forms, it is used in the form of bigluconate (Chlorhexidini bigluconas), and it is also used as a topical antiseptic and disinfectant. The composition of such products also includes jojoba oil, peppermint oil, licorice extracts, extracts of aloe vera, Japanese sophora and Centella asiatica, orange peel oil, allantoin and panthenol, vitamin E, sulfur, allantoin, eucalyptus oil, chamomile extract, camphor, bisabolol, clay (absorbs excess sebum), polyhydroxy acids, and wax micro-particles.
For Sebo-regulating action, there are used the preparations, which include zinc and sulfur. Zinc inhibits the action of the enzyme 5-alpha-reductase, which leads to reducing sensitivity of the androgen-dependent receptors, and it also plays an important role in skin regeneration, has an anti-inflammatory, astringent, drying, antiseptic and adsorbing effect, prevents hyperkeratosis and comedone formation, and also forms a protective barrier against the impact of irritating factors. Sulfur has the anti-inflammatory, antiseptic and adsorbent effects, has keratoplastic and antimicrobial properties, and it is part of the amino acids that are involved in the synthesis of the antioxidant glutathione.
The purpose of this study was to develop the remedy for acne spot treatment at the initial stage of the disease in the form of creams and solutions, using biologically active substances mostly of natural origin.
Results and their discussion. An emulsion base, when producing creams, contained: distilled monoglycerides (which are both an emulsifier and a stabilizing substance), cetyl palmitate (with its properties, it is an analogue of animal spermacet), stearin (an emulsifier and stabilizer), Carbomer 940 (stabilizer, gelling agent), methyl and propyl esters of gallic acid, and desalted water.
Substances of plant and natural origin were mainly used as biologically active components, for example in the first version:
1. Salicylic acid 2%, 2. Lactic acid 3%. 3. Gly-colic acid 3%. 4. Mandelic acid 3%. 5. Dry extract from aloe leaves 2%. 6. Dry extract of chamomile flowers 2%. 7. Eucalyptus essential oil 0.5%. 8. Tea tree essential oil 2%. 9. Chlorhexidine bigluconate 0.05%. 10. Medical sulfur 4%. 11. Zinc acetic acid mixed with zinc oxide (in equal amounts) 1%. 12. Sea buckthorn oil 3%.
Taking into account the individual peculiarities of the patients and the incompatibility of salicylic acid and resorcinol in the cream formulation, a similar amount of resorcinol is used in the second version of cream instead of salicylic acid.
Creams have been studied according to [10]. A physical form is an indiscrete mass that does not contain impurities. The color is white with a yellowish-reddish tinge. It smells like a fragrance component. A mass fraction of water and volatile substances is not less than 75%. The stability of the emulsion was determined in accordance with GOST 29188.3 (State Standard). When determining the colloidal stability after centrifugation in the test tubes, no separation of water or oil phases is observed. When determining the thermal stability, after the aging of cream in a test tube at a temperature of40-42 °C, no separation was observed as well for 24 hours.
Additionally, the following studies were conducted: the spread test was carried out according to the methodology [11]; measurement of the diameters of the formed spots (45-55 mm) showed that cream must be quite easily applied onto the skin, which is
confirmed by the test on a group of volunteers (the authors of the article).
The osmotic properties of cream were studied on a dialysis model in a glass tube with a diameter of 30 mm, one end of which was closed by a dialysis cellophane film 0.40 mm thick. The temperature during the experiment was 37 °C. The value of osmotic activity as a percentage of the initial weight of cream was determined in 4 hours.
Investigation of bioavailability was carried out using the method of diffusion in a 10%-gelatin within 24 hours at a temperature of 37 °C. Results indicate that the values ofboth osmotic activity and bioavail-ability meet the necessary requirements.
The stability time of creams was determined by their aggregative stability and the absence of mold. These parameters remained unchanged during 1.5 years of storage of samples at a temperature of 18-20 °C. According to manual observations, the developed cream is well absorbed without leaving oily sheen on the skin, and besides, it softens, moisturizes and improves skin suppleness and elasticity, and normalizes fat balance. When spreading a cream within 5 days onto the inner flexura ofthe elbow joint ofthe volunteers twice a day, no allergic reactions were observed.
The formulation of solutions has also been developed in two versions. In the first version:
1. Salicylic acid 2.0%, 2. Lactic acid 3%. 3. Gly-colic acid 3%. 4. Almond acid 5%. 5. Dry extract from aloe leaves 2%. 6. Eucalyptus essential oil 0.05%. 7. Tea tree essential oil 2%. 8. Chlorhexidine bigluconate 0.05%. The solvent is a 90%-ethyl alcohol.
In the second version, based on the above, a similar amount of resorcinol was used instead of salicylic acid. The stability of the solutions was assessed according to the following parameters: physical form - a transparent liquid, color - with a slight yellowish-brownish tinge, smells like ethyl alcohol and tastes with a little sour like ethyl alcohol, pH is not more than 6.5.
According to manual observations, the solutions were quickly absorbed, without leaving the marks on the skin, and normalizing fat balance. When applying
solutions in an amount of up to 3 ml. no allergic reactions were observed on the inner flexura of the elbow joint of the volunteers twice a day within 5 days. The cream and solutions are applied directly to separate inflammatory foci, soothe the skin, relieve itching, reduce skin redness, and accelerate the healing process.
Conclusion. The compositions of creams and solutions have been developed in several versions for acne spot treatment, the biologically active part of which consists of substances mainly of plant and natural origin. All the developed versions are not allergic and show a sufficiently high medicinal activity.
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