SLOW QUASIKINETIC CHANGES IN WATER-LACTOSE COMPLEXES DURING STORAGE
Keywords:Release-active forms of antibodies, Slow kinetic transitions, X-ray fluorescence spectroscopy, FTIR, Lactose monohydrate, Supramolecular complexes
Objective: To investigate kinetic changes in the spectral characteristics by Fourier Transform Infrared spectroscopy (FTIR) of water-lactose complexes (SMC), derived during the manufacturing process of the drug, containing release-active forms of antibodies.
Methods: lactose monohydrate substance, saturated with release-active forms of affinity-purified polyclonal rabbit antibodies to recombinant human interferon-gamma (RA forms of Abs); tablets produced from this substance by direct compression after the addition of excipients (microcrystalline cellulose, magnesium stearate). Powdered and tableted placebo samples saturated with technologically processed water or phosphate-buffered saline, as well as with intact ethanol were used as control. Kinetic changes in SMC were studied using an Agilent Cary 630 FTIR spectrophotometer with a diamond ATR accessory (Agilent Technologies, USA). We used the method of X-ray fluorescence spectroscopy (EDX-7000 Shimadzu energy dispersive X-ray fluorescence spectrometer) to track changes in the fluorescence signal at certain wavelengths. The range of measured elements–11Na-92U.
Results: Control of some technological characteristics of the obtained active substance (moisture, flowability) and dosage form (mean mass, disintegration rate) was used as indirect indicators of quality, but they did not allow reliably distinguishing intact lactose from the saturated one. Long-period oscillations on FTIR spectra were characteristic for all types of samples; oscillations occur at approximately two-week intervals; S/N indices were more stable for samples of RA forms of Abs than for placebo samples. On some days, the substance saturated with RA forms of Abs significantly differed from the intact lactose powder. The kinetics of the X-ray fluorescence intensity at certain wavelengths indicates the possibility of a periodic cooperative trigger transition of the system. Reversible conformational transitions are observed for powders on the 30th and 130th days (Kα 3.313 keV). For tablets at Kα 3.313 keV and Kα 1.740 keV small changes were visualized on those days (100–110th day) when hysteresis phenomena were recorded in the IR spectra of these samples.
Conclusion: As a result, the evidence for a long-period dramatic conformational mobility of the water-lactose complex was obtained. Based on the data on the semiannual kinetics of IR spectra, a universal criterion for the identity of lactose powder saturated with RA forms of Abs was obtained. Also, it was confirmed that the lactose conformation state was changed by saturation with RA forms of Abs.
Don ЕS, Emelyanova AG, Yakovleva NN, Petrova NV, Nikiforova MA, Gorbunov EA, et al. Dose-dependent antiviral activity of released-active form of antibodies to interferon-gamma against influenza A/California/07/09(H1N1) in murine model. J Med Virol 2017;89:759-66.
Epstein O. The spatial homeostasis hypothesis. Symmetry 2018;10:103.
Geppe NА, Gorelov АV, Shamsheva OV, Sitnikov IG, Sitnikova EP, Steshin V Yu, et al. Prevention of acute respiratory viral infections and influenza in children during the peaks of seasonal morbidity: the results of the international double-blind placebo-controlled randomized clinical trial. Ros Vest Perinatol I Pediatr 2020;65:109–20.
Uspenskaya EV, Pleteneva TV, Syroeshkin AV, Tarabrina IV. Preparation, characterization, and studies of physicochemical and biological properties of drugs coating lactose in fluidized beds. Int J Appl Pharm 2020;12:272-8.
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. https://doi.org/10.1155/2018/8905471
Syroeshkin AV, Uspenskaya EV, Pleteneva TV, Morozova MA, Maksimova TV, Koldina AM, et al. Mechanochemical activation of pharmaceutical substances as a factor for modification of their physical, chemical and biological properties. Int J Appl Pharm 2019;11:118-23.
Shin SH, Chung S, Sanii B, Comolli LR, Bertozzi CR, De Yoreo JJ. Direct observation of kinetic traps associated with structural transformations leading to multiple pathways of S-layer assembly. Proc Natl Acad Sci USA 2012;109:12968-73.
Davies JS, Coombes D, Horne CR, Pearce FG, Friemann R, North RA, et al. Functional and solution structure studies of amino sugar deacetylase and deaminase enzymes from staphylococcus aureus. FEBS Lett 2019;593:52-66.
Sahu ID, McCarrick RM, Lorigan GA. Use of electron paramagnetic resonance to solve biochemical problems. Biochemistry 2013;52:5967-84.
Grishina MP, Syroeshkin AV, Maximova TV, Kostygina MN, Pleteneva TV. X-ray fluorescence determination of zinc. J Trace Elem Med Biol 2017;41:16.
European Pharmacopoeia 8.0 V.1-2. Strasbourg: Council of Europe; 2014.
Jiang Y, Li X, Morrow BR, Pothukuchy A, Gollihar J, Novak R, et al. Single-molecule mechanistic study of enzyme hysteresis. ACS Cent Sci 2019;5:1691-8.
Bunkin NF, Shkirin AV, Penkov NV, Chirikov SN, Ignatiev PS, Kozlov VA. The physical nature of mesoscopic inhomogeneities in highly diluted aqueous suspensions of protein particles. Phys Wave Phen 2019;27:102-12.
Chikramane PS, Kalita D, Suresh AK, Kane SG, Bellare JR. Why extreme dilutions reach non-zero asymptotes: a nanoparticulate hypothesis based on froth flotation. Langmuir 2012;28:15864-75.
Agranovich D, Ishai PB, Katz G, Bezman D, Feldman Y. Dielectric spectroscopy study of water dynamics in frozen bovine milk. Colloids Surf 2016;141:390-6.
Levy E, Puzenko A, Kaatze U, Ishai PB, Feldman Y. Dielectric spectra broadening as the signature of dipole-matrix interaction. II. Water in ionic solutions. J Chem Phys 2012. DOI:10.1063/1.3691183
Bohne C. Supramolecular dynamics. Chem Soc Rev 2014;43:4037-50.
Wang Y, Yuzawa T, Hamaguchi H, Toscano JPJ. Time-resolved IR studies of 2-naphthyl (carbomethoxy) carbene: reactivity and direct experimental estimate of the singlet/triplet energy gap. Am Chem Soc 1999;121:2875–82.
Menssen RJ, Tokmakof A. Length-dependent melting kinetics of short DNA oligonucleotides using temperature-jump IR spectroscopy. J Phys Chem B 2019;123:756−67.
Marukhlenko AV, Morozova MA, Pleteneva TV. Neutron flow effect on metabolic characteristics of Artemia salina cysts. Trace Elem Electrolytes 2018;35:221-4.
Syroeshkin AV, Tarabrina IV, Morozova MA, Marukhlenko AV, Zlatskiy IA, Makarova MP. Possible mechanisms of relations between the thermal neutrons field and biosphere. Sci World J 2020. DOI:10.1155/2020/2175296.
Michaels TCT, Bellaiche MMJ, Hagan MF, Knowles TPJ. Kinetic constraints on self-assembly into closed supramolecular structures. Sci Rep 2017;7:12295.
Syroeshkin AV, Bakeeva LE, Cherepanov DA. Contraction transitions of F1-F0 ATPase during catalytic turnover. Biochim Biophys Acta Bioenerg 1998;1409:59-71.