Thermodynamic dissociation constants of risedronate using spectrophotometric and potentiometric pH-titration

Abstract

Risedronate inhibits bone resorption in diseases like osteoporosis, Pagets disease, tumor bone diseases or the malfunction of phosphocalcium metabolism. The acid-base properties of risedronate in an aqueous solution have been studied in a pH range from 2 to 12 and can be described in terms of four dissociation steps: pK a,2 , pK a,4 , pK a,5 (related to the dissociation of POH groups) and pK a ,3 related to the dissociation of protonated amino group NH 3 +. The mixed dissociation constants were determined at different ionic strengths I = 0.02 to 0.20 mol dm-3 KCl and of 25°C and 37°C using pH-spectrophotometric and pH-potentiometric titration methods. Determination of group parameters L0, HT might lead to false estimates of common parameters pK a ;therefore, the computational strategy employed is important. A comparison between the two programs ESAB and HYPERQUAD demonstrated that the ESAB program provides a better fit of potentiometric titration curve. The thermodynamic dissociation constants pK Ta were estimated by a nonlinear regression of (pK a , I) data and a Debye-Hückel equation at 25°C and 37°C, pK Ta ,2 = 2.37 (1) and 2.44 (1), pK Ta ,3 = 6.29 (3) and 6.26 (1), pK Ta ,4 = 7.48 (1) and 7.46 (2) and pKT a,5 = 9.31 (7) and 8.70 (3) at 25°C and 37°C using pH-spectroscopic data and pK Ta ,2 = 2.48 (3) and 2.43 (1), pK Ta ,3= 6.12 (2) and 6.10 (2), pK Ta ,4 = 7.25 (2) and 7.23 (1) and pK Ta ,5 = 12.04 (5) and 11.81 (2) at 25°C and 37°C. The ascertained estimates of three dissociation constants pK a ,3, pK a,4 , pK a,5 are in agreement with the predicted values obtained using PALLAS. © Versita Sp. z o.o.