Preview

Fine Chemical Technologies

Advanced search

Development of a nasal spray containing aminocaproic acid and a copolymer of N-vinylpyrrolidone and 2-methyl-5-vinylpyridine for use in the prevention of influenza and other viral respiratory infections

https://doi.org/10.32362/2410-6593-2020-15-1-67-75

Full Text:

Abstract

Objectives. Prevention of influenza and viral respiratory infections is one of the major public health problems today. The aim of the study was to develop the formulation and production conditions for a nasal spray that can be used in the prevention of influenza and other viral respiratory infections, based on aminocaproic acid and a copolymer of N-vinylpyrrolidone and 2-methyl-5-vinylpyridine.

Methods. The influence of pH and temperature on the transparency of the copolymer solution was investigated using a turbidimeter to determine the optimal pH for the dosage form. The pH value was determined using a pH meter equipped with a combined glass electrode. The presence or absence of opalescence in the solution was determined visually, whereas the dynamic viscosity of the solution was determined at 25.0±0.5°С using a rotational viscometer. The optimal temperature and mixing speeds were selected as part of the technological development process. Quantitation of the active substances in the resulting drug was conducted using a previously reported high performance liquid chromatography method. A preliminary evaluation of the drug’s shelf life was performed via stability studies using the accelerated aging method.

Results. Drug stability was ensured when the pH range of the dosage form was between 5.5 and 6.2. The addition of a thickening agent is not advisable due to undesired interactions between the excipients and the active substances during storage. Ideally, the drug composition for nasal use was aminocaproic acid (1 wt %) and the copolymer (0.5 wt %) in aqueous solution. A phosphate buffer solution with pH 5.5 was selected as the solvent for the dosage form to ensure the stability of the drug solution and ease-of-use without any disruptions in the normal functioning of the cilia in the nasal cavity. The optimal technology for drug production was determined, and the control parameters for this process were highlighted. Drug stability studies conducted via the accelerated aging method revealed that the estimated shelf life of the dosage form was 2 years.

Conclusions. A new formulation and optimized production conditions were developed for a drug based on aminocaproic acid and a copolymer of N-vinylpyrrolidone and 2-methyl-5-vinylpyridine, in the form of a nasal spray, for the prevention of influenza and other viral respiratory infections.

About the Author

A. S. Karpova
Institute of Pharmaceutical Technology
Russian Federation

Anastasiya S. Karpova, Senior Quality Specialist.

of. 1, 21, Skolkovskoe shosse, Moscow, 121353



References

1. Svyatchenko S.V., Durymanov A.G., Kolosova N.P., Gudymo A.S., Goncharova N.I., Torzhkova P.Y., Bulanovich Y.A., Epanchintseva A.V., Danilenko A.V., Marchenko V.Y., Sysoeva A.V., Susloparov I.M., Tregubchak T.V., Ryzhikov A.B., Maksyutov R.A., Ilicheva T.N. Severe cases of seasonal influenza in Russia in 2017-2018. Journal of microbiology epidemiology immunobiology. 2019;(4):58-64 (in Russ.). https://doi.org/10.36233/0372-9311-2019-4-58-64

2. Kiselev O.I., Marynich I.G., Sominina A.A. (eds.). Gripp i drugie respiratornye virusnye infektsii: epidemiologiya, profilaktika, diagnostika i terapiya (Influenza and other respiratory viral infections: epidemiology, prevention, diagnosis and therapy). Saint Petersburg: Borges; 2003. 245 p.

3. Dondurey E.A., Obraztsova E.V., Semiletko Y.S., Ovchinnikova N.V., Golovacheva E.G., Osidak L.V., Afanasyeva O.I. ARVI antiviral therapy in children in modern clinical practice. Meditsinskiy sovet = Medical Council. 2019;(2):183-187 (in Russ.). https://doi.org/10.21518/2079-701X-2019-2-183-187

4. Cheshik S.G. Influenza. Detskie infektsii = Infant Infections. 2005;(4):56-63 (in Russ.).

5. Ghori M.U., Mahdi M.H., Smith A.M., Conway B.R. Nasal Drug Delivery Systems: An Overview. Am. J. Pharm. Sci. 2015;3(5):110-119. doi:10.12691/ajps-3-5-2

6. Degenhard M.А., Gerallt W.U., Birkhoff M.S. Intranasal Drug Administration — An Attractive Delivery Route for Some Drugs. Drug Discovery and Development – From Molecules to Medicine. IntechOpen. 2015;(13):300-318. http://dx.doi.org/10.5772/59468

7. Karpova A.S., Kochkina Y.V., Kedik S.A. The antiviral activity study of complex drug with aminocapronic acid for prevention of influenza and ARVI. Razrabotka i registratsiya lekarstvennykh sredstv = Drug Development & Registration. 2019;8(2):22-26 (in Russ.). https://doi.org/10.33380/2305-2066-2019-8-2-22-26

8. Evseeva А.S., Kochkina Yu.V., Krasilnikov I.V., Kedik S.A., Eremin D.V., Suslov V.V. Antiviral and immunomodulating combination based on aminocaproic acid and a copolymer of 2-methyl-5-vinylpyrilin and <i>N</i>-vinylpyrrolidone: patent 2669810 RF. Appl. 21.06.2017, publ. 16/10/.2018. Bull. Number 29 (in Russ.).

9. Evseeva A.S., Vorfolomeeva E.V., Kochkina Yu.V., Kedik S.A., Vostrov I.A. A method for the quantitative determination of aminocaproic acid when it is combined with a copolymer of 2-methyl-5-vinylpyridine and <i>N</i>-vinylpyrrolidone by HPLC: patent 2700167 RF. Appl. 09/13/2018, publ. 09/13/2019. Bull. Number 26 (in Russ.).

10. Kravchenko I.A. Sposoby vvedeniya lekarstvennykh preparatov v organizm. Intranazal՚noe vvedenie lekarstvennykh preparatov (Methods of introducing drugs into the body. Intranasal administration of drugs). Odessa: Astroprint; 2009. 164 p. ISBN 978-966-190-128-4 (in Russ.).

11. Kundoor, V., Dalby, R.N. Effect of Formulation- and Administration-Related Variables on Deposition Pattern of Nasal Spray Pumps Evaluated Using a Nasal Cast. Pharm. Res, 2011;28(8):1895-1904. https://doi.org/10.1007/s11095-011-0417-6

12. Sakaeva I.V., Bunyatyan N.D., Kovaleva E.L., Sakanyan E.I., Mitkina L.I., Prokopov I.A., Shelekhina E.S., Mitkina Y.V. The main approaches to the study of drug stability: domestic and international experience. Vedomosti Nauchnogo centra ekspertizy sredstv medicinskogo primeneniya = The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products. 2013;(3):8-11. (in Russ.).


Supplementary files

1. Viscosity–velocity curves of samples 4 and 5 at 25ºС.
Subject
Type Research Instrument
View (72KB)    
Indexing metadata
2. This is to certify that the paper titled Development of a nasal spray containing aminocaproic acid and a copolymer of N-vinylpyrrolidone and 2-methyl-5-vinylpyridine for use in the prevention of influenza and other viral respiratory infections commissioned to Enago by Anastasiya S. Karpova has been edited for English language and spelling by Enago, an editing brand of Crimson Interactive Inc.
Subject CERTIFICATE OF EDITING
Type Other
View (409KB)    
Indexing metadata

A novel nasal spray was developed for the prevention of influenza and other viral respiratory infections. The spray contains aminocaproic acid and a copolymer of N-vinylpyrrolidone and 2-methyl-5-vinylpyridine. The viscosity of different nasal spray compositions was analyzed to determine the optimal formulation. The nasal spray can be stored for up to 2 years without any efficacy loss.

For citation:


Karpova A.S. Development of a nasal spray containing aminocaproic acid and a copolymer of N-vinylpyrrolidone and 2-methyl-5-vinylpyridine for use in the prevention of influenza and other viral respiratory infections. Fine Chemical Technologies. 2020;15(1):67-75. https://doi.org/10.32362/2410-6593-2020-15-1-67-75

Views: 179


ISSN 2410-6593 (Print)
ISSN 2686-7575 (Online)