ABSTRACT
Objective To determine equilibrium solubility and apparent partition coefficient of salicylic acid at 25 ℃,and to provide a theoretical basis for design and preparation of its formulation.Methods Equilibrium solubility and apparent partition coefficient (Papp) of salicylic acid were respectively investigated in water,hydrochloric acid solution (pH 1.0) and phosphate buffer solution system (pH 2.0,3.0,4.0,5.0,6.0,7.0,7.8) at 25 ℃.The shake flask method and HPLC were used.The column was Waters C18 (4.6 mm ×250 mm,5 μn) with the mobile phase as methanol-0.1％ phosphoric acid water (47:53).The column temperature was room temperature.The flow rate was 1.0 mL·min-1.The detection wavelength was 270 nm and injection volume was 20 μL.Results Equilibrium solubility of salicylic acid was (2.205 ±0.020) mg·mL-1 at 25 ℃ in Water and its Papp was (6.18 ±0.08).The solubility were (1.169 × 10-3 ±7.40 × 10-6),(2.250 ±0.010),(2.410±0.010),(2.694 ±0.003),(5.208 ±0.010),(5.826 ±0.006),(6.255 ±0.030),(3.353 ±0.070) mg·mL-1,respectively,at hydrochloric acid solution (pH 1.0) and phosphate buffer solution system (pH 2.0,3.0,4.0,5.0,6.0,7.0,7.8),and the corresponding Papp were (16.39 ±0.19),(4.23 ±0.07),(6.03 ±0.11),(5.56 ±0.10),(1.25 ±0.01),(0.27 ± 0.001),(0.08 ± 0.001) and (0.07 ± 0.002),respectively.Conclusion The solubility of salicylic acid increases and its oil-water partition coefficient declines with pH value increasing.Salicylic acid is slightly soluble in water and oil.It belongs to Class Ⅳ drug in Biopharmaceutics Classification System (BCS).