KINETIC-STUDY OF THE SOLID-STATE PHOTOLYTIC DEGRADATION OF 2 POLYMORPHIC FORMS OF FUROSEMIDE

In this paper some aspects influencing the solid-state photolytic degradation of two polymorphic forms of furosemide were investigated. Powder samples of the two polymorphic forms were exposed to prolonged UV irradiation, direct sunlight, in a normal and nitrogen atmosphere. The solid-state photolytic degradation of furosemide followed apparent first-order kinetics as described by a model consisting of nucleation and growth periods with eventual deceleration as it reached a maximum fraction degraded. Kinetic calculations revealed that this bilateral first-order degradation process was best described by a power law dependence (n = 2) of the fraction decomposed (alpha) on time (t) for the nucleation period and first-order kinetic degradation with an asymptote for the growth and deceleration period (Prout-Tompkins model). Overall, the rate constants during the nucleation period were significantly smaller than the growth period. Form I was photochemically more stable than form II, especially under a nitrogen atmosphere (t1/2 50 h). The photolytic degradation of form II was not influenced by the presence of oxygen (t1/2 35 h under normal atmospheric conditions and 38 h in a nitrogen atmosphere). After exposure to sunlight 4-chloro-5-sulphamoylanthranilic acid (CSA) was found in significant concentrations in samples taken from both forms I and II. Photolytic degradation of furosemide form II led to the formation of mainly CSA in the presence of nitrogen and CSA and other unidentified products in the presence of oxygen.