Abstract
Objective: Study physicochemical properties and activity of biotechnological drugs coating lactose particles in fluidized beds for the development of a prospective approach of their identification.
 Methods: Lactose monohydrate as pharmaceutical excipient; affinity-purified polyclonal rabbit antibodies to recombinant human interferon-gamma as a drug substance; Pilotlab fluid bed apparatus was used for lactose powder saturation with solutions of pharmaceutical substances to the point of granulation (pelletizing); inverse light scattering method (2D-LS) for analysis of micron vibrations frequency spectra of samples surfaces for light intensity distribution in time by values of d1, d2, d3 primary descriptors; low angel and dynamic laser light scattering (LALLS, DLS) methods for distribution of lactose-water (LW) supramolecular complexes into volume fractions (micron "size spectra"), using the Master Sizer 2000 instrument and Zeta Sizer Nano ZS instrument in the nanoscale; Spirotox method for research of biological activity to determine the activation energy (Ea) values of cell death in solutions of tested samples.
 Results: Changes in 2D-LS scattering time on sample surfaces, described by topological descriptors, made it possible to clearly differentiate the intact lactose from fluidized samples by specific corridors in coordinates di=F(t). The calculated activation energy (Ea) values of cell biosensor death process in solutions of drugs coating lactose allow to characterize the biological activity of it in the initial (by Ea increase) and activated state (by Ea decrease) after the creation of intra-laboratory transmucosal conditions. A unique dimensional spectrum of LW complexes in the nanoscale range was obtained by DLS. The differences between samples in the distribution of LW complexes in the size range from 1 µm to 125 µm was showed by LALLS.
 Conclusion: The developed approach, including Сhemometrics, laser and biotesting methods can be used for qualitative the analysis tasks as well as for analytical control of the fluidization process in cases where identifiable pharmaceutical substances are not distinguishable by traditional analytical methods.
Highlights
In the epoch of a sharp rise in industrial volumes of drug production, the process of "homogeneity" of its creation with necessary functional characteristics acquires special importance [1, 2]
Changes in 2D light scattering time of specimen surfaces described with topological descriptors di =F(t) made it possible to determine definitely the intact lactose sample, which hadn’t been involved in the process of fluidization as a result of the form individual " corridors" in di=F(t) coordinates
For differentiation of drugs after lactose coating in the fluidized bed, we used the analysis of the frequency composition of the measured 2D-LS signal based on Fourier transform
Summary
In the epoch of a sharp rise in industrial volumes of drug production, the process of "homogeneity" of its creation with necessary functional characteristics acquires special importance [1, 2]. The pharmaceutical and technological aspect of the quality of coating of solid dosage forms is of great importance, which is the final operation in the drug production. At modern pharmaceutical manufactures for application of coatings on firm medical products (powders, pills, dragee) fluidized bed (FB) devices were used, which work is based on laws of hydrodynamics and heat exchange in dispersed mediums [3,4,5]. Fluidization consists in the rapid formation of isolated droplets of a drug substance in the transport flow of liquids ‒ a type of reaction micro-cameras [6]. There are forces influencing the droplet formation at the interface. Due to the competition between these two forces, particles suspended in the fluid migrate across streamlines when flowing downstream, and equilibrate at a specific location in the channel’s cross-section Due to the competition between these two forces, particles suspended in the fluid migrate across streamlines when flowing downstream, and equilibrate at a specific location in the channel’s cross-section (fig. 1)
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