Physico-chemical properties of oxybutynin

Abstract

The dissociation constant, partition coefficient (octan-1-ol–water), solubility and stability of oxybutynin (OXY)in vitro were studied at 37 °C and an ionic strength of 0.15 using high-performance liquid chromatography. The dissociation constant was determined by potentiometry in methanol–water. The pK_a value of 8.04 was extrapolated to 0% methanol concentration and agreed with that evaluated from the solubility. The apparent partition coefficients and the solubilities were measured at various pH values by means of the shaking method. The intrinsic partition coefficient for the non-ionized and ionized forms were determined as 7.8 × 10⁴ and 5.0, respectively. The solubility was directly determined as 1.2 × 10^–2 mg ml^–1 for the free base of OXY and as 77 and 0.8 mg ml^–1 at pH 1 and 6, respectively. In buffer of pH from 1 to 8, OXY is very stable and the degradation is almost negligible, whereas it is rapidly degraded at alkaline pH. The hydroxide ion catalysed rate constant is estimated to be 2.1 mol^–1 l min^–1; e.g., its half-life of degradation at pH 12.0 is 14 min.