EFFECT OF FORMALDEHYDE FORMATION ON DISSOLUTION STABILITY OF HYDROCHLOROTHIAZIDE BEAD FORMULATIONS

An immediate release hydrochlorothiazide (HCTZ) bead formulation (form ulation A) containing drug, lactose hydrous, sodium starch glycolate ( Primojel(R)) and microcrystalline cellulose (Avicel(R) PH 101), and a control formulation (formulation B), without Primojel(R), were exposed to 22 degrees C/80% RH, RT/ambient RH, 40 degrees C/75% RH, and 40 de grees C/ambient RH in open petri dishes for 4 weeks. After the exposur e, formulation A exhibited a significant decrease in dissolution rate under all conditions except 40 degrees C/ambient RH. In contrast, no c hange in dissolution rate was observed for formulation B. It is possib le that the decrease in dissolution rate of formulation A was due to t he formation of a trace amount of formaldehyde due to hydrolysis of HC TZ in the humid environment and its subsequent reaction with Primojel( R), which resulted in formation of an insoluble product and a reductio n in disintegrating power of the Primojel(R). In a simulated storage e nvironment of high humidity in Conway cells and using the diffusion me thod, significantly less formaldehyde was detected in the formulation A beads compared to the formulation B beads (P = 0.03). This may indic ate that formaldehyde present in the formulation A was partially consu med through a reaction with Primojel(R). In both formulations, a signi ficantly greater amount of formaldehyde was detected in beads containi ng smaller particles of HCTZ (P = 0.02). The formation of formaldehyde and its reaction with Primojel(R) seemed to be confined to the expose d surfaces of the beads since compression of the exposed beads into ta blets resulted in faster dissolution of HCTZ.