18Научные междисциплинарные исследования
5. Рыжова, Н.А. Экологическое воспитание дошкольников с позиции новой парадигмы / Н.А.Рыжова // Дошкольное воспитание. - 2016. - № 7. - С. 15-25.
УДК 615.07
Губанова Людмила Борисовна Gubanova Lyudmila Borisovna
кандидат фармацевтических наук, доцент кафедры фармацевтической химии candidate of pharmaceutical sciences, Associate Professor of the Department of Pharmaceutical Chemistry
Позднякова Анастасия Евгеньевна Pozdnyakova Anastasia Evgenievna
Аспирант Postgraduate student
Пятигорский медико-фармацевтический институт-филиал ФГБОУ ВО ВолгГМУ
Минздрава России, г. Пятигорск, Россия Pyatigorsk Medical and Pharmaceutical Institute-branch of the Volgograd State Medical University of the Ministry of Health of Russia, Pyatigorsk, Russia
ПРЕДВАРИТЕЛЬНЫЙ СПЕКТРОФОТОМЕТРИЧЕСКИЙ АНАЛИЗ ЛЕКАРСТВЕННОЙ ФОРМЫ ПРОТИВОАЛЛЕРГИЧЕСКОГО
ДЕЙСТВИЯ
SPECTROPHOTOMETRY ANALYSIS OF THE DRUG FORM OF ANTI-ALLERGIC ACTION
Аннотация. Одной из основных проблем фармакотерапии является развитие различных осложнений, лидирующие позиции которых занимают аллергические реакции, значительно ухудшающие качество жизни. Аллергический ринит - самый распространенный вид хронического ринита, которым страдают 40 % населения, 10-20% из которых отмечают ухудшение качества жизни. Фармакологическая коррекция аллергического ринита носит комплексный, ступенчатый характер. С целью поиска эффективных лекарственных препаратов для лечения аллергических ринитов был разработан предварительный состав назального спрея, содержащего фексофенадина гидрохлорид и моноаммонийную соль
Международная научно-практическая конференция глицирризиновой кислоты (глицирам). Для подбора оптимальных соотношений вспомогательных компонентов и разработки методик дальнейшего анализа лекарственной формы были проведены предварительные спектрофометрические определения. Предварительными исследованиями установлено, что максимум поглощения при 218±2 нм принадлежит фексофенадина гидрохлориду, при 256±2 нм - моноаммонийной соли глицирризиновой кислоты.
Annotation. One of the main problems of pharmacotherapy is the development of various complications, the leading positions of which are occupied by allergic reactions that significantly worsen the quality of life. Allergic rhinitis is the most common type of chronic rhinitis, which affects 40% of the population, 10-20% of whom report a deterioration in the quality of life. Pharmacological correction of allergic rhinitis is complex, stepwise. In order to search for effective drugs for the treatment of allergic rhinitis, a preliminary composition of a nasal spray containing fexofenadine hydrochloride and a monoammonium salt of glycyrrhizic acid (glycyram) was developed. To select the optimal ratios of auxiliary components and develop methods for further analysis of the dosage form, preliminary spectrometric determinations were carried out. Preliminary studies have established that the absorption maximum at 218 ± 2 nm belongs to fexofenadine hydrochloride, at 256 ± 2 nm - to the monoammonium salt of glycyrrhizic acid.
Ключевые слова, спектрофотометрический метод, методика анализа, спрей, антигимистанное действие.
Key words: spectrophotometric method, analysis technique, spray, antihimistic action.
One of the main problems of pharmacotherapy is the development of various complications, the leading positions of which are occupied by allergic reactions that significantly worsen the quality of life. Allergens are almost everything: medicines, food, household items, plant pollen [1].
Allergic rhinitis is an inflammation of the nasal cavity mucous caused by exposure to the allergen. Allergic rhinitis is the most common type of chronic rhinitis, which affects 40 % of the population, 10-20% of which report a deterioration in the quality of life [3]. The chronic form of the disease and its convertion to moderate-severe and severe forms can pose a danger to the optimal functioning of the respiratory system, as well as cause more serious pathologies of an allergic genesis, such as bronchial asthma. Pathological changes observed during the manifestation of allergic rhinitis are non-specific, typical pathophysiological reactions and may contribute to the
Научные междисциплинарные исследования development of obstructive diseases of the bronchopulmonary system of non-allergic origin [4].
A significant epidemiological component of allergic rhinitis, the complex pathogenesis, a significant number of complications and adverse processes associated with the underlying disease (obstructive sleep apnea, nasal polyps, otitis media). According to this rational pharmacotherapy of allergic rhinitis one of the important components of the strategy for improving the quality of life of the population, which is a priority task of modern health care. The first line of allergic rhinitis treatment is the use of oral antihistamines that do not have a sedative effect (cetirizine, loratadine, desloratadine). However, the oral route of administration of these drugs limits the onset time of the therapeutic effect at the 25-30 minutes level, which, without a doubt, is not an acceptable indicator for the treatment of acute diseases [5]. Opposite, medicines that are used intranasally have a large «therapeutic range».
In order to find effective medications for the treatment of allergic rhinitis, a preliminary composition of a nasal spray containing Fexofenadine hydrochloride and the monoammonium salt of glycyrrhizic acid (glycyram) was developed. To select the optimal ratios of auxiliary components and develop optimal analysis methods of the dosage form spectrophotometric determination of active substances was conducted.
Materials and methods: the substance Fexofenadine hydrochloride (USA) and the monoammonium salt of glycyrrhizic acid (Russia) were used. For spectrophotometric determination, a SF-2000 spectrophotometer with quartz cuvettes in optical path length of 10 mm was used. Weighing was performed on the analytical balance "GOSMETR". We were guided by the general pharmacopoeia monograph of the General Pharmacopoeia Monograph 1.2.1.1.0003.15 Spectrophotometry in the ultraviolet and visible regions [2].
Results and discussion
Fexofenadine in medicines is used in the salt form - Fexofenadine hydrochloride. The nasal dose of Fexofenadine has not been established. However, based on the daily oral dose of 120 mg and the ratio of nasal / oral doses of other antihistamines, it can be assumed that the nasal dose of Fexofenadine should be in the range of 1 to 5 mg /
Международная научно-практическая конференция nostril. Therefore, for a liquid drug with a dose volume of 0.1 ml, a concentration of Fexofenadine from 10 to 50 mg / ml is required. The main problem in the development of nasal or ophthalmic drug forms of Fexofenadine hydrochloride is the limited solubility of the molecule[6].
According to regulatory documents Fexofenadine hydrochloride is soluble in ethyl alcohol, methyl alcohol (in any ratio), as well as in dilute solutions of alkalis (for example, a solution of 5% sodium hydroxide) [7]. The solubility test of fexofenadine was carried out in accordance with General Pharmacopoeia Monograph 1.2.1.0005.15. "Solubility" of the State Pharmacopoeia XVI edition at a fixed temperature of 20 ± 20° C, using solvents of different polarity [8]. Found that fexofenadine is poorly soluble in water, very easily soluble in ethanol 95% and in 5% sodium hydroxide solution, soluble in polyethylene glycol and readily soluble in propylene glycol.
In accordance with the current regulatory documentation, the authenticity of the monoammonium salt of glycyrrhizic acid is established by a qualitative chemical reaction to glycyrrhizic acid (by the precipitation reaction from aqueous solutions with diluted sulfuric acid).
To identify Fexofenadine hydrochloride and glycyram in the composition, their maximal absorbance rate in the UV- region of the spectrum were used.
It is known from the literature that a solution of Fexofenadine in 5% sodium hydroxide solution has a maximum absorbance at 218±2 nm, and a solution of glycyram in alkalis at 256±2 nm.
To determine the specificity of the spectrometric method for identifying the ingredients of the composition, the following solutions were prepared: a solution of Fexofenadine in 5% sodium hydroxide solution (1), a solution of glycyram in 5% sodium hydroxide solution (2), and a mix-solution of Fexofenadine and glycyram. The spectra of these solutions were recorded in the UV region of the spectrum (figures 13).
Научные междисциплинарные исследования
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J Vx.
Длина волны, им
Fig. 1. Spectral scanning curve of Fexofenadine hydrochloride in 5% sodium hydroxide solution (maximum absorbance at 220 nm)
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Ji 9
Fig.2. Spectral scanning curve of a glycyram in a 5% sodium hydroxide solution
(maximum absorbance at 258 nm)
1,000
0,750
0.500
Погл. Б.
0,250
0,000
? I JL
/ \ s \ \
f A \ ......................................I....................................\...............J ......... .......
____J
200,00
250.00
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300,00
350,00
Fig. 3. Spectral scanning curve for a mix-solution Fexofenadine hydrochloride and glycyram in a 5% sodium hydroxide solution (absorbance maxima at 220
nm and 258 nm)
Международная научно-практическая конференция
From figures 1-3, the maximal absorbance of Fexofenadine, glycyram and their
mix-solutions do not differ significantly, therefore, the identification of the spray components can be performed by UV spectroscopy. The maximum absorption of the spray solution should be at a wavelength of 218±2 nm and at a wavelength of 256±2 nm.
For further development of methods for quantitative determination of active substances (Fexofenadine hydrochloride and glycyram) at this stage, we registered the absorption spectrum of the drug solution in the UV- region of the spectrum (figure 3).
As follows from the figure, the absorption spectrum in the UV- region has two maximal absorbance: at a wavelength of 218±2 nm and at a wavelength of 256±2 nm.
Conclusion
Study have established that the maximal absorbance at 218±2 nm belongs to Fexofenadine hydrochloride, at 256±2 nm - for monoammonium salt of glycyrrhizic acid. Accordingly, it is possible to use the method of spectrophotometric determination to develop methods for qualitative and quantitative analysis of the dosage form. Research in this area will continue taking into account the validation requirements.
Библиографический список:
1. Алейникова Н.С., Хаджиева З.Д. Изучение классификационных признаков заболеваний верхних дыхательных путей (обзор 1) // Успехи современной науки и образования. - 2017. -Т. 6.- № 3. - с. 199-202.
2. Государственная фармакопея РФ XIV издания. - Том 1. - 2018. -ОФС.1.2.1.1.0003.15 Спектрофотометрия в ультрафиолетовой и видимой областях [Электронный ресурс] Режим доступа: http://femb.ru (дата обращения:15.10.2020)
3. Small P. Keith P., Small P.K., Kim H. Allergic rhinitis, Allergy, Asthma, and Clinical Immunology // Official Journal of the Canadian Society of Allergy and Clinical Immunology. - 2018. - 14(2).- Р. 51. doi:10.1186/s13223-018-0280-7
Научные междисциплинарные исследования
4. Dykewicz M.S., Hamilos D.L. Rhinitis and sinusitis // The Journal of Allergy and Clinical Immunology. - 2010. - №125. - P. 103-S115. doi: 10.1016/j.jaci.2009.12.989
5. Campu P., Rondon C., Gould G.P., Barrionuevo G. P., Blanca M. Local IgE in non-allergic rhinitis// Clinical & Experimental Allergy. - 2015. - №45 (5). - P. 872881. doi: 10.1111/cea.12476.
6. Хаджиева З.Д., Чумакова В.А., Губанова Л.Б. Разработка методики количественного определения фексофенадина в субстанции спектрофотометрическим методом// Научные ведомости Белгородского государственного университета. Серия: Медицина. Фармация. - 2015. - № 22 (219). - С. 158-163.
7. Хаджиева З.Д. Определение глицирризиновой кислоты в сырье и препаратах солодки голой методом ВЭЖХ // Вестник новых медицинских технологий. -2006. -Т. 13.- № 3. -С. 188-190.
8. Государственная фармакопея РФ XIV издания. - Том 1. - 2018. -ОФС.1.2.1.0005.15 Растворимость [Электронный ресурс] Режим доступа: http://femb.ru (дата обращения: 10.10.2020)
© Л. Б. Губанова, А. Е. Позднякова , 2020
