Solid Dosage Forms of Nootropic Action Based on Pantogam and Succinic Acid

Keywords: Pantogam, succinic acid, tablets, complexometry, high-performance liquid chromatography, validation.

Abstract

In recent years, research related to the search and study of the mode of action of new and used in medicine nootropic agents has been carried out at a high rate. The research related to the search for new combined drugs of nootropic action based on the substances of d-gamma-Pantothenate of calcium and succinic acid, which have neurometabolic, atigipoxic, and adaptogenic properties, is of interest. The purpose of this study was to develop and justify the optimal composition and manufacturing technologies of tablets with nootropic effect and standardise the proposed dosage forms containing Pantogam
and succinic acid.
The method for preparing the tablet mixture is as follows: all components were weighed in the required amount, Pantogam was placed in the mortar, then succinic acid was added and ground to a consistent white powder. The tablets were pressed on a manual press at a pressure of 120 mn/m2. The coating was applied on a laboratory fluidised bed unit with a single nozzle in a perforated drum with a volume of 1000 ml. The obtained tablets were evaluated according to the requirements for State Pharmacopoeia XIII and State Pharmacopoeia XIV. The comparison of the Pantogam tablets with succinic acid
obtained by direct pressing and by wet granulation showed that the method of direct pressing allows obtaining tablets with good physical and mechanical properties and bioavailability. The methods based on acid-base titration and spectrophotometric determination were developed for the quantitative determination of Pantogam in tablets. The method of quantitative determination of succinic acid in dosage forms was validated.
Based on the study of physicochemical and technological properties of substances and excipients, the compositions and technology for obtaining tablets containing Pantogam and succinic acid were justified and developed. It was found that solid-phase interactions occur with the combined presence of Pantogam and succinic acid in the tablets. The methods of qualitative and quantitative analysis of dosage forms containing Pantogam and succinic acid based on complexometric titration and high-performance liquid chromatography were developed. The procedure of validation of the method for determining succinic acid by HPLC in the developed dosage forms confirmed the validity of the proposed method.

 

 

 

REFERENCES

1. Voronkov A. V., Pozdnyakov D. I., Nigaryan S. A.
Сerebroprotective effect of some phenolic acids under
conditions of experimental brain ischemia. Pharmacy
& Pharmacology. 2019;7(6): 332–339. DOI: https://doi.org/10.19163/2307-9266-2019-7-6-332-338
2. Cornelis E., Gorus E., Beyer I., Bautmans I., De
Vriendt P. Early diagnosis of mild cognitive impairment
and mild dementia through basic and instrumental
activities of daily living: development of a new
evaluation tool. PLoS Med. 2017;14(3): e1002250. DOI:
https://doi.org/10.1371/journal.pmed.1002250
3. Wang P., Wang W., Hu Y., Li Y. Prolonged soluble
epoxide hydrolase reactivity in brain endothelial cells
is associated with long cognitive deficits in sepsis.
Molecular Neurobiology. 2020;57(6): 2846–2855. DOI:
https://doi.org/10.1007/s12035-020-01925-2
4. Sun M. K. Potential therapeutics for vascular
cognitive impairment and dementia. Current
Neuropharmacology. 2018,16(7): 1036–1044. DOI:
https://doi.org/10.2174/1570159X15666171016164734
5. Lowry E., Puthusseryppady V., Coughlan G.,
Jeffs S., Hornberger M. Path integration changes as a
cognitive marker for vascular cognitive impairment?
– A pilot study. Frontiers in Human Neuroscience.
2020;21(14): 131. DOI: https://doi.org/10.3389/fnhum.2020.00131
6. Beggiato S., Borelli A. C., Ferraro L., Tanganelli S.,
Antonelli T., Tomasini M. C. Palmitoylethanolamide
blunts amyloid-b42-induced astrocyte activation and
improves neuronal survival in primary mouse cortical
astrocyte-neuron co-cultures. J. Alzheimer's Disease.
2018;61(1): 389–399. DOI: https://doi.org/10.3233/jad-170699
7. Moretti R., Caruso P., Storti B., Saro R.,
Kassabian B., Sala A., Giannini A., Gazzin S. Behavior
in subcortical vascular dementia with sight pathologies:
visual hallucinations as a consequence of precocious
gait imbalance and institutionalization. Neurological
Sciences. 2020;14: 131. DOI: https://doi.org/10.1007/s10072-020-04445-y
8. Chen N., Yang M., Guo J., Zhou M., Zhu C., He L.
Cerebrolysin for vascular dementia. Cochrane Database
of Systematic Reviews. 2019;11. DOI: https://doi.org/10.1002/14651858.CD008900
9. Solleiro-Villavicencio H., Rivas-Arancibia S.
Effect of chronic oxidative stress on neuroinflammatory
response mediated by CD4+T cells in neurodegenerative
diseases. Frontiers in Cellular Neuroscience. 2018;12:
114. DOI: https://doi.org/10.3389/fncel.2018.00114
10. Voronkov A. V., Shabanova N. B., Voronkova M. P.,
Lysenko T. A. Study of cerebrotropic dose-dependent
effect of pyrimidine derivative under pir-9 code against
the background of experimental cerebral ischemia in
rats. Pharmacy & Pharmacology. 2018;6(6): 548–567.
DOI: https://doi.org/10.19163/2307-9266-2018-6-6-548-567 (In Russ.)
11. Muzyko E. A., Tkacheva G. A., Perfilova V. N.,
Matvienko L. S., Naumenko L. V., Vasil’eva O. S.,
Tyurenkov I. N. Bulletin of experiment effects of gaba
derivatives on anxious and compulsive behavior in
offspring of rats with experimental preeclampsia.
Bulletin of Experimental Biology and Medicine.
2020;168(4): 457–464. DOI: https://doi.org/10.1007/s10517-020-04731-x
12. Wilms W., Woźniak-Karczewska M., Corvini P. F.,
Chrzanowski Ł. Nootropic drugs: Methylphenidate,
modafinil and piracetam – Population use trends,
occurrence in the environment, ecotoxicity and removal
methods. Chemosphere. 2019;233: 771–785. DOI:
https://doi.org/10.1016/j.chemo-sphere.2019.06.016
13. Fekete S., Hiemke C., Gerlach M. Dose-related
concentrations of neuro-/psychoactive drugs expected
in blood of children and adolescents. Therapeutic Drug
Monitoring. 2019;42(2): 315–324. DOI: https://doi.org/10.1097/FTD.0000000000000685
14. Saad C. Y., Fogel J., Rubinstein S. Awareness
and knowledge among internal medicine resident
trainees for dose adjustment of analgesics and
neuropsychotropic medications in CKD. South Med J.
2018;111(3): 155–162. DOI: https://doi.org/10.14423/smj.0000000000000781
15. Woźniak-Karczewska M., Čvančarová M.,
Chrzanowski Ł., Kolvenbach B., Corvini P.F.,
Cichocka D. N. Isolation of two ochrobactrum sp.
strains capable of degrading the nootropic drug -
Piracetam. New Biotechnology. 2018;43: 37–43. DOI:
https://doi.org/110.1016/j.nbt.2017.07.006
16. Zavadenko N. N. , Suvorinova N. Yu. ,
Zavadenko A. N. Attention deficit hyperactivity
disorder in children: effectiveness of hopantenic acid
pharmacotherapy. Voprosy prakticheskoj pediatrii.
[Clinical Practice in Pediatrics] 2018;13(2): 11–18. DOI:
https://doi.org/10.20953/1817-7646-2018-2-11-18
17. Voronina T. A., Litvinova S. A. Pharmacological
effects and clinical application of Pantogam and
Pantogam active. Zhurnal nevrologii i psikhiatrii im. S.
S. Korsakova. 2017;117(8): 132–139. DOI: https://doi.org/10.17116/jnevro201711781132-139
18. Zavadenko N. N., Guzeva V. I., Gaynetdinova D. D.,
Davydova L. A., Zavadenko A. N., Romanova T. A.
Pharmacotherapy of psychomotor developmental
delay in 6–12 months preterm infants with hypoxicischemic
encephalopathy (the double-blind
comparative multicenter placebo-controlled study).
Zhurnal nevrologii i psikhiatrii im. S. S. Korsakova.
2019;119(10): 30–39. DOI: https://doi.org/10.17116/jnevro201911910130
19. Stylianou E., Pateraki C., Ladakis D., Cruz-
Fernández M., Latorre-Sánchez M., Coll C., Koutinas A.
Evaluation of organic fractions of municipal solid
waste as renewable feedstock for succinic acid
production. Biotechnology for Biofuels. 2020;13(1):
13:72. DOI: https://doi.org/10.1186/s13068-020-01708-w
20. Jiang M., Ma J., Wu M., Liu R., Liang L., Xin F.,
Zhang W., Jia H., Dong W. Progress of succinic acid
production from renewable resources: Metabolic and
fermentative strategies. Bioresource Technology.
2017;245: 1710–1717. DOI: https://doi.org/10.1016/j.biortech.2017.05.209
21. Chetverikova A. G., Kanygina O. N., Alpysbaeva
G. Z., Yudin A. A., Sokabayeva S. S. Infrared
spectroscopy as the method for determining structural
responses of natural clays to microwave exposure.
Kondensirovannye Sredy i Mezhfaznye Granitsy =
Condensed Matter and Interphases. 2019;21(3): 446–
454. DOI: https://doi.org/10.17308/kcmf.2019.21/1155
22. Seredin P. V., Goloshchapov D. L., Nikitkov K. A.,
Kashkarov V. M., Ippolitov Y. A., Jitraporn (Pimm) V.
Application of synchrotronic IR-microspectroscopy
for analysis of integration of biomimetic composites
with native dental tissues. Kondensirovannye sredy i
mezhfaznye granitsy = Condensed Matter and Interphases.
2019;21(2): 262–277. DOI: https://doi.org/10.17308/kcmf.2019.21/764 (In Russ., abstract in Eng.)
23. Eltsova N. O., Budko E. V. Application of HPLC
with optical and thermal methods in complex analysis
of inter-component interactions of pharmaceutical
compositions. Sorbtsionnye i Khromatograficheskie
Protsessy. 2019;19(4): 474–480. DOI: https://doi.org/10.17308/sorpchrom.2019.19/786 (In Russ.,
abstract in Eng.)

Downloads

Download data is not yet available.

Author Biographies

Denis A. Slivkin, Peoples Friendship University of Russia, 6 Miklukho-Maklaya ul., Moscow 117198, Russian Federation

Candidate of the Department of
General Pharmaceutical and Biomedical Technology
of the Medical Institute, Peoples Friendship University
of Russia, Moscow, Russian Federation; e-mail:
slivkin@pharm.vsu.ru.

Yulia A. Polkovnikova, Voronezh State University, 1 Universitetskaya pl., Voronezh 394018, Russian Federation

PhD in Pharmacy, Associate
Professor of the Department of Pharmaceutical
Technology and Pharmaceutical Chemistry, Faculty of
Pharmacy, Voronezh State University, Voronezh,
Russian Federation; e-mail: juli-polk@mail.ru

Alena S. Belenova, Voronezh State University, 1 Universitetskaya pl., Voronezh 394018, Russian Federation

PhD in Biology, Assistant of the
Department of Pharmaceutical Chemistry and
Pharmaceutical Technology, Voronezh State University,
Voronezh, Russian Federation; e-mail: alenca198322@mail.ru

Aleksey I. Slivkin, Voronezh State University, 1 Universitetskaya pl., Voronezh 394018, Russian Federation

DSc in Pharmacy, Professor, Head
of the Department of Pharmaceutical Chemistry and
Pharmaceutical Technology, Voronezh State University,
Voronezh, Russian Federation; e-mail: slivkin@pharm.vsu.ru.

Svetlana N. Suslina, Peoples Friendship University of Russia, 6 Miklukho-Maklaya ul., Moscow 117198, Russian Federation

PhD in Pharmacy, Head of the
Department of General Pharmaceutical and Biomedical
Technology of the Medical Institute, Peoples Friendship
University of Russia, Moscow, Russian Federation

Anastasia A. Kashchavtseva, Voronezh State University, 1 Universitetskaya pl., Voronezh 394018, Russian Federation

Engineer, Department
of Pharmaceutical Technology and Pharmaceutical
Chemistry, Faculty of Pharmacy, Voronezh State
University, Voronezh, Russian Federation; e-mail:
farmnastya92@gmail.ru

Published
2020-09-24
How to Cite
Slivkin, D. A., Polkovnikova, Y. A., Belenova, A. S., Slivkin, A. I., Suslina, S. N., & Kashchavtseva, A. A. (2020). Solid Dosage Forms of Nootropic Action Based on Pantogam and Succinic Acid. Kondensirovannye Sredy I Mezhfaznye Granitsy = Condensed Matter and Interphases, 22(3), 388-396. https://doi.org/10.17308/kcmf.2020.22/2999
Section
Статьи