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Медико-биологический
информационный портал
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Vol. 26, Art. 1 (pp. 1-24) | 2025
Optimization of chitosan microspheres obtaining method in enteral medications development
Ustinova T.M., Gusak T.I., Vengerovich N.G., Neeshpapa A.D.
FSBI “The State Scientific Research Testing Institute of Military Medicine” of the Ministry of Defense of the Russian Federation
Brief summary
Purpose. Optimization of a chitosan microspheres-based drug carrier obtaining method in terms of the process conditions’ effect on particle formation by the water-in-oil emulsion method with subsequent glutaraldehyde cross-linking for increased bioavailability of oral pharmaceutical forms on a model substance. Materials and method. Size distribution of the obtained chitosan microspheres was explored using a laser light scattering particle size analyzer Malvern Mastersizer 3000; their visualization was performed using a microscope Leica DM 2500 (German), Olimpus CX41 (YI); quantitative analysis of microsphere-encapsulated drug was done using a high-performance liquid chromatograph Agilent 1260 with a quadrupole time of flight mass spectrometer Agilent 6530, Accurate-Mass Q-TOF LC/MS, and an ionization source Dual ESI. Results. The paper studied a set of process parameters influencing chitosan microspheres formation. The optimal morphology and particle size upon creation of a polymeric oral delivery system were achieved by variation of such parameters of their obtaining as the linking agent and emulsifier amounts, homogenization rate selectivity and hardening time. Chitosan microspheres were obtained by emulsion cross-linking technique using glutaraldehyde as a linking agent. The linking agent amount and hardening time exert the main influence on the formation of dense, smooth particles. Such microparticle structure was obtained by adding 5 mL of glutaraldehyde, at homogenization rate of 10000 rpm and hardening time of 120 min. Particles were characterized by a monodisperse distribution, and median size of 1150 [1145; 1165] µm. Encapsulation efficiency was analyzed by passive sorption method with drug-to-polymer ratio of 30, 50 and 70% (w/w). Streptomycin was used as a model drug. The maximum encapsulation efficiency of 22.6 [18.9; 25.5] was achieved when using drug-to-polymer ratio of 50% (w/w). Conclusion. The optimal conditions have been chosen for microspheres formation, when they contain the maximum streptomycin loading, and were obtained by the water-in-oil emulsion method. Microparticles had spherical shapes, smooth surfaces with a minor porosity, and a median size of 1145-1165 µm. Particles were obtained using the following process parameters of emulsion cross-linking with glutaraldehyde: linking agent amount - 5 mL, homogenization rate - 10000 rpm, hardening time - 120 min, and drug-to-polymer ratio - 50% (w/w). Key words Microspheres; chitosan; linking agent; glutaraldehyde; water-in-oil emulsion (The article in PDF format. For preview need Adobe Acrobat Reader)  Open article in new window
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