Alfaxalone: Effect of Temperature on Complexation with 2-Hydroxypropyl-β-cyclodextrin

Phase solubility analysis is used to investigate the complex formation of alfaxalone with various cyclodextrins(2-hydroxypropyl-β-cyclodextrine [HPBCD],β-cyclodextrin [BCD] and2-hydroxypropyl-γ-cyclodextrin [HPGCD]).The complexationwith HPBCD was studied in more detail by looking at the effect of temperature on the stability constants using phase solubility analysis. HPLC-analysis was used to measure the dissolved amount of alfaxalone.The solubility of alfaxalone increases linearly with increasing concentration of cyclodextrin, suggesting the formation of a 1 : 1 complex. For the parent BCD the complex starts precipitating out of solution when the solubilizer concentration exceeds 0.25% making the unsubstituted BCD less useful for the preparation of solutions of alfaxalone. Substituted cyclodextrins do not form insoluble complexes with alfaxalone. The complexation constant for BCD and HPBCD are comparable in magnitude, but for HPGCD, the constant is substantially lower.