EFFECTS OF VARIOUS FORMULATION FACTORS ON DISSOLUTION STABILITY OF AZTREONAM, HYDROCHLOROTHIAZIDE, AND SORIVUDINE CAPSULES

A split-split-plot 3(2) X 2(2) factorial design was used to study the effects of capsule filling machine and formulation factors such as lac tose type, lubricant concentration, and capsule shell size on the diss olution stability of 50 mg potency hydrochlorothiazide (HCTZ), sorivud ine (BV-araU), and aztreonam capsules packaged in HDPE bottles and sto red under different conditions. It was observed that neither magnesium stearate concentration nor the type of capsule machine used to fill t he capsule shells had any effect on dissolution stability of capsules of all three drugs for up to 6 months of storage at 50 degrees C. For aztreonam, neither capsule shell size nor the type of lactose had any effect on dissolution stability. On the other hand, HCTZ size no. 1 ca psules demonstrated better dissolution stability than size no. 2 capsu les. Moreover, dissolution stability of capsules of sorivudine and HCT Z on storage at 50 degrees C, 40 degrees C/75% RH, and 40 degrees C wa s dependent on the type of lactose used. HCTZ capsules containing Fast -Flo(R) lactose, hydrous lactose, or anhydrous lactose showed up to 45 , 25, and 10% decrease in dissolution, respectively, compared to initi al values, at the 20 min dissolution time point after 6 months storage at 50 degrees C. The extent of decrease in the dissolution rate was l ess under the conditions of storage at 40 degrees C/75% RH and 40 degr ees C. Similar effects of decrease in the dissolution rate with the di fferent types of lactose were observed with sorivudine, although to a much lesser degree compared to HCTZ capsules. No decrease in dissoluti on rate was observed for any drug after 20 months storage at 30 degree s C. It was hypothesized that the slight decrease in dissolution rate of sorivudine capsules was due to significant caking of the capsule co ntents in the presence of the moisture liberated from the excipients a nd the capsule shells. For aztreonam capsules, the caking of their con tents was without any discernable effect on dissolution because of the high aqueous solubility. In contrast, for HCTZ capsules, changes in d issolution rate were far too pronounced to be attributed to caking onl y.