CC BY
6021. Burmistrova L.A. Physical and chemical analysis and biochemical assessment of biologically active drone growth. Extended abstract of Candidate's thesis. Ryazan'; 1999. Russian.
22. Risau W. Mechanisms of angiogenesis. Nature. 1997;386:671-4.
23. Komisar OD. Homogenate of Drone Licks as a Sum of Erroneous Statements and Unresolved Issues. Kharkiv: NFaU; 2006;6:87-92. Ukrainian.
24. Barker SA, Foster AB, Lamb DC, Hodgson N. Identification of 10-hydroxy-D2-decenoic acid in Royal Jelly. Nature. 1999;183(4666):996-7.
25. Budnykova NV. Improving the technology of production and storage of drone brood of honey bees. Extended abstract of Candidate's thesis. Divovo; 2011. Russian.
26. Finke MD. Nutrient composition of bee brood and its potential as human food. Ecol. Food Nutr. 2005;44:257-70.
27. Mardanly SG, Pomazanov VV, Kiseleva VA, Rogozhnikova EP, Romanov BK, Burmistrova LA, Budnikova NV, invertor. [Tincture of drone brood and method of obtaining tincture of drone brood]. Russia patent №0002690516. 2019 Jul 4. Russian.
28. Lazaryan DS. Comparative amino acids analysis of bee bread. Pharm. Chem. J. 2002;36:680-68.
29. Ghosh S, Sohn HY, Pyo SJ, Jensen AB, Meyer-Rochow VB, Jung C. Nutritional composition of Apis mellifera Drones from Korea and Denmark as a potential sustainable alternative food source: Comparison between developmental stages. Foods. 2020;9:389.
ANALYSIS OF THE RANGE OF SEMISOLID MEDICINES IN THE FORM OF GELS ON THE PHARMACEUTICAL MARKET OF UKRAINE AND EXCIPIENTS IN THEIR COMPOSITIONS
Blazhko I.
I.Horbachevsky Ternopil National Medical University, Student of the Pharmaceutical Faculty, Ternopil, Ukraine
Hroshovyi T.
I.Horbachevsky Ternopil National Medical University, DSc, Prof. Department of Pharmacy Management, Economics and Technology, Ternopil, Ukraine
Chubka M.
I. Horbachevsky Ternopil National Medical University, Ph.D., Assoc. Prof of the Department of Pharmacy, Ternopil, Ukraine
Pavliuk B.
I. Horbachevsky Ternopil National Medical University, PhD (Pharmacy), Assis. Prof. of the Department of Pharmacy Management, Economics and Technology,
Ternopil, Ukraine
ABSTRACT
As of December 2019, 133 gels were registered on the pharmaceutical market of Ukraine._When analyzing the range of gels by composition, it was determined that monocomponent gels prevail over combined ones, the share of which is 60.2 %. It is determined that in the domestic pharmaceutical market the share of imported gels is higher (63.2 %) compared to the number of domestic gels (36.8 %). Gels for dermal use occupy 78.2 % of the pharmaceutical market of all semisolid medicines in the form of gels. In the analysis of excipients used in gel formulations, it was determined that their technology uses gelling agents, solvents, stabilizers, emulsifiers (such as o/w and w/o), pH regulators, solubilizers, preservatives, flavor and odor correctors.
Keywords^Soft dosage forms, gels, excipients, pharmaceutical market, range.
Semisolid medicines currently occupy a leading position among other forms of drug, which registered in the pharmaceutical market of Ukraine. Gels, which occupy a central place in the arsenal of drugs for the treatment of dermatological diseases, and are widely used in cosmetic practice, are becoming increasingly popular among semisolid dosage forms (SDF) [1].
Today, gels are one of the most promising dosage forms for modern pharmacy. Gels - characterized by certain advantages over other SDF, namely this form contributes to the uniform distribution of active substances on the wound surface, mucous membranes and their release from the dosage form, penetration into the deepest tissues. This form is easy to use, safe for the skin, cost-effective and characterized by moisturizing, cooling and emollient effects. This dosage form may contain one or more active pharmaceutical ingredients, and are single-, two- or multiphase dispersion systems
with a liquid dispersion medium, the viscosity of which is due to the presence of gelling agents [2, 3].
According to the order of the Ministry of Health of Ukraine dated 20.07.2006 № 500 "On approval of lists of names of dosage forms and packaging for medicinal products" gels as a dosage form are used in various groups of drugs, in particular, gel for external use belong to the category of skin and transdermal drugs. Group of oromucosal agents' available gingival gels, gels for the oral cavity [4].
Depending on the nature of the dispersed medium, gels are classified into hydrogels, oleogels, also known as alcohols, benzogels and acetone gels. The most common in pharmacy are hydrogels and oleogels.
In hydrophilic gels, the base usually consists of water, glycerin or propylene glycol, as well as thickening agents such as carbomers, poloxamers, cellulose derivatives etc. Hydrogels are translucent gels that have
low adhesion to the wound surface, quickly absorb exudate and toxins, provide constant humidity and temperature, and promote the transport of oxygen molecules into the wound. The basis of lipophilic gels consists of vaseline oil with polyethylene or fatty oils and thickening agents such as aluminum or zinc soap, colloidal silicon dioxide [3].
By origin, gels are classified into natural (gelatin, agar-agar, gums, etc.) and artificial (cellulose and its derivatives, nitrocellulose and others).
By purpose, gels are divided into oral (most often used in pediatrics and geriatrics), external use, as well as for eye, ear, nasal, vaginal, cervical, rectal, urethral, and dental [1-2, 5-8].
The purpose of the work: study of the range of drugs in the form of gels registered on the pharmaceutical market of Ukraine as of 2019 and analysis of excipients that are part of them.
Materials and methods: The study used methods of systematic and
paper information. The object of the study was information on registered SDF on the national market as of December 2019 according to the State Register of Medicinal Products of Ukraine, posted on the website "Regulatory documents of the Ministry of Health of Ukraine", in the directory of drugs Compendium [911].
Results and discussion.
Semisolid drugs that are allowed to be used on the territory of Ukraine and released from pharmacies and their structural subdivisions were subject to study. According to the results of research, as of December 2019, the pharmaceutical market of Ukraine registered 492 names of soft drugs, among which the share of drugs in the form of gel is 27.1 % that is 133 drugs.
When analyzing the range of gels by composition, it was determined that monocomponent gels, the share of which is 60.2%, prevail over combined (39.8%).
statistical analysis of electronic and
Figure 1 - Distribution of gels according to the composition of the drug
Gels as a dosage form are used in various diseases, drugs in the form of gels belong to different pharmacological groups. When analyzing the entire range of gels presented on the pharmaceutical market of Ukraine by purpose, it was determined that gels for dermal use occupy the main share (78.2 %), while other gels have a 90
78,2
80 70 60 50 40 30 20 10 0
small percentage of the range (oromucosal gels - 6.8 %, eye gels - 4.6 %, nasal gels - 3.0 %, vaginal and en-docervical gels - 3.0%, rectal gels - 0.7 %, oral gels -3.0 %, dental gels - 0.7 %).
6,8 3 4,6 3 1 A « A H
■ 3 0,7 j. 0,7 _L
¿s-
Figure 2 - The structure of the range of gels by purpose, %
It is determined that in the pharmaceutical market (49 SDF), the shares of which are 63.2 % and 36.8 %, of Ukraine SDF in the form of gels of import produc- respectively.
Figure 3 - Distribution of gels by domestic and foreign production
The leaders among the countries that import drugs in the form of gels to Ukraine are Germany, India and France. The share of soft dosage forms of the leading countries
% (Germany), 17.9 % (India) and 9.5 % (France), and the share of other countries whose imports of gels to Ukraine are insignificant is 41.7 %.
represented on the Ukrainian market is 30.9
other countries United Kingdom 10,5
Figure 4 - Importing countries of drugs in the form of gels, %
Among domestic producers, the leaders in the production of soft drugs in the form of gels are the LLC "Pharmaceutical Company "Zdorovye"", PJSC "Pharmaceutical Company "Darnitsa"", PJSC SIC "Borshchahivskiy CPP", OJSC "Kievmedpreperat", PJSC "Chervona zirka" and PJSC "Fitofarm".
Since the choice of excipients, justification of the feasibility, and combination is an important stage in the pharmaceutical development of drugs in general and the specifics of drug forms, we specifically analyzed the range of excipients in the registered gels. The list of excipients that can be used in the production of drugs in Ukraine, regulated by the order of the Ministry of Health from 19.06.2007 № 339 and includes 586 excipients and 38 dyes [12].
In the study of excipients used in the compositions of gels, it was determined that their technology uses thickening agents, solvents, stabilizers, emulsifiers (type o/w and w/o), pH regulators, solubilizers, preservatives, flavor and odor correctors.
The technology of gels uses natural (gelatin, agar-agar, gums, etc.) and synthetic (cellulose and its derivatives, nitrocellulose) gel bases. It is determined that in drug formulations in the form of gels registered in Ukraine, pharmaceutical manufacturers prefer such hy-drophilic bases: polyethylene glycol gels (polyethylene oxides), cellulose derivative - sodium carboxymethyl-cellulose, carmellose sodium, methylcellulose, copoly-mers of acrylic acid (carbomers 974P, 934 P, 940, 980), proxanol ("poloxamers") and gelatin-glycerol bases. These substances do not have an irritating and sensitizing effect, are compatible with almost all active pharmaceutical ingredients except phenols. Alginic acid and its salts, carbomers, cellulose derivatives, proxa-nols, polyethylene glycol (PEG) 1500-8000, aerosil, gelatin and others are most often introduced into the composition of soft dosage forms [1, 13].
Surfactants stabilize soft forms, increasing their stability by reducing the surface tension at the interface between the two liquid phases. The choice of surfactants is carried out taking into account the magnitude of
their hydrophilic-lipophilic balance. Often in order to obtain a certain pharmacological effect and maximum stability of drugs use several emulsifiers with different values of this indicator [1, 5, 14].
Liquids used in the manufacture of soft medicines include purified water, non-aqueous hydrophilic solvents (eg, ethyl alcohol, glycerin, polyethylene glycol 400, etc.), non-aqueous hydrophobic solvents (including Vaseline oil, benzyl benzoate, fish oil, etc.). Etha-nol, glycerin, propylene glycol, dimexid and other solvents can be used to improve the dispersion of drugs in heterogeneous systems. These excipients accelerate and improve the dissolution of the active ingredients, and, due to greater lipophilicity compared to water, improve the penetration of drugs through biological membranes. Polyethylene glycol stabilizes soft forms by preventing the interaction of molecules of active substances with each other and with molecules of excipients. Substances that improve absorption (cetyl palmi-tate, cetyl alcohol, ethyl alcohol), increase the penetration of substances through the skin [15].
When developing gels, it is necessary to pay attention to excipients that can change the physicochemical properties of the drug. The most common of these substances are antioxidants and antimicrobial preservatives [16, 17].
Preservatives must ensure the microbiological purity of the dosage form throughout the period of their use, have reliable antimicrobial activity, must be compatible with active pharmaceutical ingredients and other excipients. An example of incompatibility, which results in precipitation and reduced antimicrobial action, maybe the combined use of carbomer and ben-zalkonium chloride in the gel.
Today, the range of antimicrobial preservatives that are approved for use is quite wide, but in the development of soft drugs, manufacturers prefer parabens (nipagin, nipazol), benzoic acid and its salts, sorbic acid and its salts, phenylethyl alcohol.
The most common antioxidants used by modern pharmaceutical manufacturers in SDF are ascorbic acid and its salts, a-tocopherol, disodium edetate, butylhy-droxyanisole and butylhydroxytoluene, sodium metabisulfite [14, 16].
Antioxidants are included in the dosage forms only if it is proven that their use is mandatory. In the case of reducing the likelihood of oxidative processes in the drug by optimizing the production process, the feasibility of using antioxidants is not justified.
To give the gels an aesthetic appearance and aroma, dyes and fragrances are added to their composition. Flavor sweeteners, in particular, aspartame, sucrose, sucrose cocoate, saccharin and its salts, cycla-mates, are added to the composition of gels used in dentistry.
Substances of plant origin are used as correctors of smell and taste, especially in dental gels (essential oils of mint, orange, pine needles, cloves, alcoholic extracts of medicinal plant raw materials), as well as synthetic substances identical to natural (menthol, vanillin, thymol).
Conclusions: The range of soft drugs registered on the pharmaceutical market of Ukraine was studied
and it was established that as of December 2019, 492 names of soft drugs were registered, among which the share of drugs in the form of gel is 27.1 % that is 133 drugs. When analyzing the range of gels by composition, it was determined that monocomponent gels, the share of which is 60.2 %, prevail over combined ones. It is determined that in the pharmaceutical market of Ukraine soft drugs in the form of gels of imported production prevail over gels of domestic production, which generally reduces the availability of such drugs.
In the analysis of excipients used in the compositions of gels, it was determined that their technology uses gelling agents, solvents, stabilizers, emulsifiers (type o/w and w/o), pH regulators, solubilizers, preservatives, flavor and odor correctors.
Analyzing the pharmaceutical market of soft drugs, namely gels, we can conclude that the expansion and increase in the range of gels of domestic production remains a topical issue today.
Conflicts of interest: authors have no conflict of interest to declare
References
1. Vons BV, Chubka MB, Groshovyi TA. Market analysis of semisolid dosage forms registered in Ukraine and research of excipients included to their formulas. Pharmaceutical review. 2015;1:55-61. doi: 10.11603/2312-0967.2015.1.3766.
2. Glushchenko OM, Polova ZhM. [Market analysis of wound healing semisolid drugs]. Farmatsevt chasop. 2019;4:51-6. doi: 10.11603/23120967.2019.4.10684. Ukrainian.
3. The State Pharmacopoeia of Ukraine: in 3 vol. Kharkiv: Ukrainian Scientific Pharmacopoeia Center of Quality of Medicinal Products. Ed.2. Vol. 3. [Derzhavna Farmakopeya Ukrayiny: v 3 t. / DP «Ukrayinskyy naukovyy farmakopeynyy tsentr yakosti likarskykh zasobiv». - 2-e vyd.] Kharkiv: Ukrainian Scientific Pharmacopoeia Center of Quality of Medicinal Products. 2015. Ukrainian.
4. On approval of the Classifier of dosage forms: the Order of the Ministry of Health of Ukraine of July 07, 2006 No 500. Available from: https://www.apteka.ua/article/3482
5. Pavliuk BV, Lukashiv OYa, Pokryshko OV, Chubka MB, Hroshovyi TA. Research of the preservatives' antimicrobic activity for the development of a new combined gel composition for the local treatment of burns. Pharmaceutical review. 2019;3:35-42. doi: 10.11603/2312-0967.2019.3.10409
6. Vons BV, Chubka MB, Hroshovyi TA, Stechyshyn IP. [Comparative analysis of the range of drugs for the local treatment of burns in national and foreign markets]. Pharmac Journal. 2019;4:4-11. doi: 10.32352/0367-3057.4.19.01. Ukrainian.
7. Nemchenko AS, Kukhtenko OS, Gladukh IeV. [Marketing research of the pharmaceutical market of drugs for treating varicose veins and inflammatory diseases of joints]. Sotsialna farmatsiia v okhoroni zdo-rovia. 2017;3(3):66-73. doi: 10.24959/sphhcj.17.87. Ukrainian.
8. Bhasha SA, Khalid SA, Duraivel S, Bhowmik D, Kumar KS. Recent trends in usage of polymers in the formulation of dermatological gels. Indian J Res Pharm Bio-tec. 2013;1(2):161-8.
9. Regulatory documents of the Ministry of Health of Ukraine. Available from: http://mozdocs.kiev.ua
10. State Register of Medicines of Ukraine [Electronic resource]. Available from: http://www.drlz.kiev.ua
11. Compendium Directory [Internet]. Available from: http://compendium.com.ua.
12. Ministry of Health of Ukraine. On approval of the Lists of names of excipients and dyes that are part of the drug. Order № 339. 2007 June 19. Available from: http://mozdocs.kiev.ua/view.php?id=7108.
13. Pavliuk B, Stechyshyn I, Kramar S, Chubka M, Hroshovyi T. Therapeutic efficacy of the developed gel "Xeliogel" on a burn wound model in rats. Polski merkuriusz lekarski: organ Polskiego Towarzystwa Le-karskiego. 2020;48(287):331-4.
14. Vons B, Hroshovyi T, Chubka M. Comparative study of markets of Ukraine, Poland and Russia on registered medications for local treatment of burns. Pharmaceutical Review. 2016;1:74-8.
15. Carvalho FC, Calixto G. Rheological, mechanical and bioadhesive behavior of hydrogels to optimize skin delivery system. Drug. Dev. Ind. Pharm. 2013;39(11):1750-7. doi: 10.3109/03639045.2012.734510.
16. Kaur LP, Guleri TK. Topical gel: recent approach for noveldrugdelivery. Asian Journal of Biomedical and Pharmaceutical Sciences. 2013;3(17):1-5.
17. Vons B, Melnyk Y, Skorokhoda V, Grochovuy T, Chubka M. Research of the rheological properties of the gel based on sodium alginate for the local treatment of burns. 2nd international scientific conference. Chemical technology and engineering; 2019 June 24-28; Lviv. Lviv: Polytechnic National University, 2018. p. 232-34.
АНАЛ1З ВАРТОСТ1 Л1КУВАННЯ ХВОРИХ П1СЛЯ COVID-19 НООТРОПНИМИ Л1КАРСЬКИМИ ЗАСОБАМИ В УКРАШ1
Назартна В.
Доцент кафедри ОЕФ, к.ф.н., Нацюнальний фармацевтичний унгверситет, Украгна
Куриленко Ю. Асистент кафедри ОЕФ, Нацюнальний фармацевтичний унгверситет, Украна
Попова I.
Доцент кафедри ОЕФ, к.екон.н., с.н.т., Нацюнальний фармацевтичний унгверситет, Украна
Тетерич Н. Доцент кафедри ОЕФ, к.ф.н., Нацюнальний фармацевтичний унгверситет, Украгна
Подколзта М. Доцент кафедри ОЕФ, к.ф.н., Нацюнальний фармацевтичний унгверситет, Украгна
ANALYSIS OF THE COST OF TREATMENT PATIENTS AFTER COVID-19 WITH NOOTROPIC
MEDICINES IN UKRAINE
Nazarkina V.
Associate professor of the department OEPH, candidate of pharmaceutical sciences, National University of Pharmacy, Ukraine
Kurylenko Yu. Assistant of the department OEPH, National University of Pharmacy, Ukraine
Popova I.
Associate professor of the department OEPH, PhD in Economics, Senior Researcher, National University of Pharmacy, Ukraine
Teterich N.
Associate professor of the department OEPH, candidate of pharmaceutical sciences, National University of Pharmacy, Ukraine
Podkolzina M.
Associate professor of the department OEPH, candidate of pharmaceutical sciences, National University of Pharmacy, Ukraine
