THE THE EFFECT OF THERMAL STERILIZATION AND EXCIPIENTS ON THE STABILITY OF ASCORBIC ACID IN AQUEOUS SOLUTIONS

A. V. SYROESHKIN; T. V. PLETENEVA; E. V. USPENSKAYA; O. V. LEVITSKAYA; S. S. BARSEGYAN; I. A. ZLATSKY; M. A. TRIBOT-LASPIERE

doi:10.22159/ijap.2019v11i5.34025

Authors

A. V. SYROESHKIN Peoples Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St, Moscow, 117198, Russian Federation
T. V. PLETENEVA Peoples Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St, Moscow, 117198, Russian Federation
E. V. USPENSKAYA Peoples Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St, Moscow, 117198, Russian Federation
O. V. LEVITSKAYA Peoples Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St, Moscow, 117198, Russian Federation
S. S. BARSEGYAN Russian Center for Forensic Medicine, 12/13 Polikarpova St, Moscow, 125284, Russian Federation
I. A. ZLATSKY Peoples Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St, Moscow, 117198, Russian Federation
M. A. TRIBOT-LASPIERE Peoples Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St, Moscow, 117198, Russian Federation

DOI:

https://doi.org/10.22159/ijap.2019v11i5.34025

Keywords:

L-Ascorbic acid, Heat sterilization, Sulfur (IV) excipients, Polarimetry, Electron spectrometry, Electrospray tandem mass spectrometry, Spirotox-test

Abstract

Objective: To investigate the thermal stability of aqueous solutions of L-ascorbic acid (AA) and its reactions with excipients for the improvement of the injection forms technology.

Methods: Solutions of L-ascorbic acid were prepared using deuterium depleted water (DDW-«light» water, D/H=4 ppm) and natural deionized high-ohmic water (BD, D/H=140 ppm). The optical rotation was observed using an automatic polarimeter Atago POL-1/2. Electrospray tandem mass spectra were recorded by Sciex X500R QTOF. Electronic spectra were recorded by UV-spectrometer Cary 60 (Agilent). Unicellular biosensor (Spirotox-test) was used for investigation of excipients influence on the AA biological activity. The statistical analysis was carried out using the OriginPro®9 packages.

Results: The results demonstrate the thermal instability of AA. The optical activity of injection forms of AA differs from model solutions with the same concentration and pH value but without heat treatment. Monitoring of solutions by the LC-ESI-MS/MS method made it possible to characterize the nature of some thermal decomposition products. Thermodynamic calculations and evaluation of biological activity (Spirotox-test) indicate that AA interacts with sulfite-ion by redox mechanisms. Excipients in AA aqueous solutions decrease, but DDW increases the biological object lifetime.

Conclusion: The use of the set of physicochemical and biological methods to study the effect of heat treatment of L-ascorbic acid solutions in the presence of sulfur (IV) compounds as excipients made it possible to identify decomposition products of the active pharmaceutical ingredient. The results indicate the need to exclude sterilization of the AA injection form by the thermal method and replace it with an alternative one, for example, with gamma radiation treatment.

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References

Syroeshkin AV, Pleteneva TV, Uspenskaya EV, Levitskaya OV, Tribot Laspiere MA, Zlatsky IA, et al. Polarimetric research of pharmaceutical substances in aqueous solutions with different water isotopologues ratio. Int J Appl Pharm 2018;10:243-8.

Mauludin R, Mohamad SFB, Suciati T. Formulation and characterization of ascorbyl palmitate loaded o/w microemulsion. Int J Pharm Pharm Sci 2014;6:294-8.

Davies MB, Austin J, Partridge DA. Vitamin C. Its chemistry and biochemistry. Cambridge: The Royal Society of Chemistry; 1991.

Zia R, Nazir A, Khan MKI, Maan AA, Rashida. Preparation of ascorbic acid and cholecalciferol microsponges for topical application. Int J Pharm Pharm Sci 2017;9:280-7.

Bradshaw MP, Barril C, Clark AC, Prenzler PD, Scollary GR. Ascorbic acid: a review of its chemistry and reactivity in relation to a wine environment. Crit Rev Food Sci Nutr 2011;51:479–98.

Szultka M, Buszewska Forajta M, Kaliszan R, Buszewski B. Determination of ascorbic acid and its degradation products by high-performance liquid chromatography-triple quadrupole mass spectrometry. Electrophoresis 2014;35:585–92.

Dabbagh HA, Fatemeh Azami F. Experimental and theoretical study of racemization, stability and tautomerism of vitamin C stereoisomers. Food Chem 2014;164:355–62.

Gomez RB, Roux S, Courtois F, Bonazzi C. Spectrophotometric method for fast quantification of ascorbic acid and dehydroascorbic acid in the simple matrix for kinetics measurements. Food Chem 2016;211:583-9.

Allen F, Greiner R, Wishart D. Competitive fragmentation modeling of ESI-MS/MS spectra for putative metabolite identification. Metabolomics 2015;11:98–110.

Levitskaya OV, Syroeshkin AV, Pleteneva TV. Arrhenius kinetics as a bioactivity assessment criterion for drug substances and excipients. Pharm Chem J 2016;49:779-81.

Titorovich OV, Lyulina EB, Pleteneva TV, Maksimova TV, Syroeshkin AV, Uspenskaya EV, et al. Reaction of an antioxidant (sodium sulfite) with 3-hydroxy-6-methyl-2-ethylpyridinium salts. Pharm Chem J 2015;48:842-4.

Experiment 3-1 Formulation Design and Preparation of Vitamin C Injections, Vitamin C; 2012. Available from: https://wenku.baidu.com/view/60867cc7a1c7aa00b42acb04.html?re=view. [Last accessed on 24 Apr 2019]

Pharmaceutical Medicine Technology. Available from: https://www.meddr.ru/posobie_dlya/aptechnaya_tehnologiya_lekarstv/8365. html (in Russian). [Last accessed on 05 May 2019]

Vitamin C injection and its preparation method. Available from: https://patents.google.com/patent/CN104146952A/en. [Last accessed on 05 May 2019]

Mylan Institutional LLC. Ascorbic acid-Injection, USP. For intravenous, intramuscular or subcutaneous use. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=d052.

Sultana Y. Pharmaceutical microbiology and biotechnology: sterilization Methods and Principles New Delhi: Jamia Hamdard; 2007.

Ramirez Cahero HF, Valdivia Lopez MA. Effect of gamma radiation on sugars and vitamin C: Radiolytic pathways. Food Chem 2018;245:1131-40.

Silva CB, Araujo TD, Vasconcelos RL, Paula CB, Nogueira AP, Lira AB, et al. Gamma radiation as a method for sterilization of all-in-one admixtures bags for clinical use: a study of stability. Int J Pharm Pharm Sci 2015;7:129-35.

Alberty RA, Sibley RJ, Daniels F. Physical chemistry. New York: Wiley; 1992.

Goncharuk VV, Syroeshkin AV, Zlatskiy IA, Uspenskay EV, Orekhov AV, et al. Quasichemical description of the cell death kinetics of cellular biosensor spirostomum ambigua for testing the biological activity of aqueous solutions. J Water Chem Tech 2017;39:97–102.

Goncharuk VV, Pleteneva TV, Grebennikova TV, Syroeshkin AV, Uspenskaya EV. Determination of biological activity of water having a different isotope ratio of protium and deuterium. J Water Chem-Tech 2018;40:27–34.

Goncharuk VV, Pleteneva TV, Uspenskaya EV, Syroeshkin AV. Controlled chaos: heterogeneous catalysis. J Water Chem-Tech 2017;39:325–30.

Wardhani DH, Cahyono H, Aaryanti N. Performance of glucomannan-alginate combination as a pH-sensitive excipient of vitamin C encapsulation using gelation method. Int J Appl Pharm 2019;11:185-92.

Klu MW, Addy BS, Oppong EE, Sakyi ES, Mintah DN. Effect of storage conditions on the stability of ascorbic acid in some formulations. Int J Appl Pharm 2016;8:26-31.

Hoffer LJ, Robitaille L, Zakarian R, Melnychuk D, Kavan P. High-dose intravenous vitamin c combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial. PLoS One 2015;10. Doi:10.1371/ journal.pone.0120228e0120228