MECHANOCHEMICAL ACTIVATION OF PHARMACEUTICAL SUBSTANCES AS A FACTOR FOR MODIFICATION OF THEIR PHYSICAL, CHEMICAL AND BIOLOGICAL PROPERTIES
Keywords:Pharmaceutical substances, Herbal raw material, Mechano-activation, Biological activities
Objective: Study the influence of the mechanical preparation methods (grinding, fluidization) of solid pharmaceutical substances (PS) and herbal raw material on their physicochemical properties and biological activities.
Methods: Test substances and solvents-Lactose monohydrate (DFE Pharma, Germany). Sodium chloride, bendazol hydrochloride (all Sigma-Aldrich, USA) and herbal raw material (Callisia fragrans). The dispersity and native structure of pharmaceutical substances were analyzed by several methods: optical microscopy–Altami BIO 2 microscope (Russia); low angle laser light scattering (LALLS) method (Malvern Instruments, UK); Spirotox method–Quasichemical kinetic of cell transition of cellular biosensor Spirostomum ambiguum; Fourier-transform infrared spectroscopy–the analysis in the middle IR region was carried out using an IR Cary 630 Fourier spectrometer (Agilent Technologies, USA). The analysis of dried leaves of C. fragrans before and after mechanical activation was performed using Shimadzu EDX-7000 X-ray fluorescence spectrophotometer without mineralization (Shimadzu, Japan).
Results: It was established that the mechanical change, such as dispersion and drying, alters the biological activity of PS and herbal raw materials. The observed increase in the influence of the dispersed substance on the biosensor S. ambiguum is quantitatively estimated from the values of the activation energy (obsEa), which turns to be valued 1,5 (P≤0,05) times more than for the native form substance. In the study of the dependence of the availability of chemical elements K, Ca, Zn on the degree of dispersion of herbal raw materials was established a quantitative 4-fold (P≤0,05) increase in the concentration of elements in mechano-activated raw materials.
Conclusion: By the example of the biological model of Spirotox (single-celled biosensor S. ambiguum) and herbal raw materials obtained from C. fragrans, the increase of biological activity of PS at the dispersion of initial preparations was proved.
Blaise C, Ferard JF. Small-scale freshwater toxicity investigations. Springer 2005;1:299-322.
Sonali Bharate S, Sandip Bharate B, Amrita Baja N. Interactions and incompatibilities of pharmaceutical excipients with active pharmaceutical ingredients: a comprehensive review. J Excipients Food Chem 2010;1:3-10.
Bazarov IP. Thermodynamics. Moscow: Vysshaya Shkola; 1991.
Sergeev GB. Nanochemistry. Amsterdam: Elsevier Science; 2006.
Cloves BJ, Divya B, Suman M, Venkataswamy K, Thyagaraju A. Study on phytochemicals, functional groups and mineral composition of Allium sativum (Garlic). Int J Cur Pharm Res 2017;9:42-5.
Zhu Y, Wang M, Zhang Y, Zeng J, Omari Siaw E, Yu J, et al. In vitro release and bioavailability of silybin from micelle-templated porous calcium phosphate microparticles. AAPS PharmSciTech 2016;17:1232-9.
Mulik A, Bhadekar R. Extracellular polymeric substance (EPS) from Kocuria sp. BRI 36.: a key component in heavy metal resistance. Int J Pharm Pharm Sci 2018;10:50-4.
Ivannikova EV, Zherdev VP, Boyko SS, Blynskaya EV, Turchinskaya KG, Alekseev KV. The study of pharmacokinetics and bioavailability in the creation of new original therapeutic agents with peptide structures and their optimal forms of administration. Pharmacokinet Pharmacodyn 2013;2:33.
Kripa KG, Sangeetha R, Chamundeeswari D. Pharmacognostical and physicochemical evaluation of the plant Leucas aspera. Asian J Pharm Clin Res 2016;9:263-8.
Fernandes BJD, Matthes ACS, Bighetti S, Fernandes JD, Lanchote VL, Pinto Lopes CR. Correlation between plasma tamoxifen concentration and tumor response in patients with breast cancer: at neoadjuvant treatment with tamoxifen. Int J Pharm Pharm Sci 2017;9:100-6.
Rumpf G. On the main physical issues in grinding. Frankfurt am Main: European meeting on grinding; 1962.
European Pharmacopoeia 8.0 V.1-2. Strasbourg: Council of Europe; 2014.
Syroeshkin AV, Popov PI, Grebennikova TV. Laser diffraction for standardization of heterogeneous pharmaceutical preparations. J Pharm Biomed Anal 2005;37:927-30.
Nalecz Jawecki G, Sawicki J. Toxicity of inorganic compounds in the Spirotox test: a miniaturized version of the Spirostomum ambiguum test. Arch Environ Contam Toxicol 1998;34:1-5.
Goncharuk VV, Syroeshkin AV, Zlatskiy IA, Uspenskaya EV, Levitskaya OV, Dobrovolskiy VI, et al. Quasi-chemical description of the kinetics of cell death Spirostomum ambigua biosensor for biological activity of aqueous solutions. J Water Chem Technol 2017;39:97-102.
Syroeshkin AV, Uspenskaya EV, Pleteneva TV, Morozova MA, Zlatskiy IA, Koldina AM, et al. Mechanical transformation of compounds leading to physical, chemical and biological changes in pharmaceutical substances. Sci World J 2018. Doi:10.1155/2018/8905471
Uspenskaya EV, Anfimova EV, Syroeshkin AV, Pleteneva TV. Kinetics of pharmaceutical substance solubility in water with different hydrogen isotopes content. Indian J Pharm Sci 2018;80:318-24.
Sharma DK, Singh J, Raj P. Spectrophotometric determination of propranolol hydrochloride and metoprolol tartrate in pharmaceutical dosage forms, spiked water, and biological fluids. Int J Pharm Pharm Sci 2018;10:107-15.
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.
Bykanova SN, Suzdaleva OS, Seregina OB. The use of cellular biosensor Spirostomum ambigua to characterize the biological activity of the components of pharmaceuticals. Electronic J "Investigated In Russa" 2003;3:1114-29.
Shakhtshneider TP, Myz SA, Dyakonova MA, Boldyrev VV, Boldyreva EV, Nizovskii АI, et al. Mechanochemical preparation of organic-inorganic hybrid materials of drugs with inorganic oxides. Acta Phys Pol А 2011;119:272-8.
Meor Mmr, Tripathy M, Majeed A. The prospect, promises and hindrances of statin base molecules: look back to look forward. Int J Pharm Pharm Sci 2016;8:22-33.
Avakumov EG, Boldyrev VV, Boldyreva EV. Fundamentals of the mechanical activation, mechanosynthesis, and mechano-chemical technologies. Novosibirsk: Publishing House of SB RAS; 2009.
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.
Sali S, Gondkar S, Saudagar R. A review on: atrigel-the magical tool. Int J Curr Pharm Res 2018;10:38-42.
Goncharuk VV, Pleteneva TV, Grebennikova TV, Syroeshkin AV, Uspenskaya EV, Antipova NV, et al. Determination of biological activity of water having a different isotope ratio of protium and deuterium. J Water Chem Technol 2018;40:27-34.
Goncharuk VV, Pleteneva TV, Uspenskaya EV, Syroeshkin AV. Controlled chaos: heterogeneous catalysis. J Water Chem Technol 2017;39:325–30.
McCluney Kevin E, Sabo John L. Tracing water sources of terrestrial animal populations with stable isotopes: laboratory tests with crickets and spiders. PLoS One 2010;5:1-1.
Shantanova LN, Alekseeva EA, Khobrakova VB, Radnayeva DB. Stress-protective and immunomodulatory properties of Callisia fragans wood juice. Siberian Med J 2009;3:126-9.
Chuparina EV, Gunicheva TN. State and issues of X-ray fluorescence analysis of herbal raw materials. Anal Control 2004;8:211-26.