Ds. Desai et al., EFFECT OF FORMALDEHYDE FORMATION ON DISSOLUTION STABILITY OF HYDROCHLOROTHIAZIDE BEAD FORMULATIONS, International journal of pharmaceutics, 107(2), 1994, pp. 141-147
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.