Дослідження розчинності бетаметазону дипропіонату і умов утворення його стабільних суспензій

The aim. To study the solubility of betamethasone dipropionate (BD) in mixed solvents water – propylene glycol (PG) and liquid paraffin, as well as to identify the conditions necessary for the formation of stable BD suspensions. Materials and methods. The solubility of BD in solvents water – PG was studied using spectrophotometry. The particle size distribution of BD in suspensions was analysed by laser diffraction. The suspensions and creams were subjected to optical microscopy for additional evaluation. Thermogravimetric analysis was conducted to explore the potential formation of BD crystallosolvates with PG, while differential scanning calorimetry was utilised to assess the characteristics of the dissolution processes. Additionally, the study employed the spin probe method, using a steroid spin-label. Results. The solubility of BD in water – PG solvents was found to increase with rising temperature and to increase sharply with increasing PG concentration, provided that the PG structure dominated the system. The deviations of BD solubility from additivity at 20-35°C were negative, passing through a minimum at a PG concentration of ~35% mol, above which the transition to the structure of a nonaqueous solvent occurred. An elevation in temperature to 45-55°C resulted in a positive deviation of the BD solubility from additive values at specific PG concentrations. It has been demonstrated that PG and BD do not form crystallosolvates. The process of dissolving BD in PG is exothermic, while in liquid paraffin, it is endothermic. The steroid spin probe was found to be localized in the oil phases of creams. Suspensions in which BD particles recrystallize were formed when BD crystallized from solution in PG as a result of lowering the temperature and adding water. When BD was suspended in a water ‒ PG solvent, where the water structure predominates, or in liquid paraffin (oil phase of creams), the BD particle size increased slightly, or there was no recrystallization. Conclusions. The solubility of BD in solvents water – PG is contingent upon the temperature and concentration of PG; it exhibits a marked increase when the structure of a nonaqueous solvent predominates in the system. It has been demonstrated that BD with PG does not form crystallosolvates. When BD suspensions were obtained by crystallization from a solution in PG, suspensions were formed in which BD particles recrystallized over time. In the case of BD suspensions in solvent water – PG, where the water structure predominates, or in liquid paraffin, recrystallization was practically not observed