Stability studies of the effect of crosslinking on hydrochlorothiazide release

The aim of this study was to determine the changes in the in vitro drug release from cross-linked hard gelatin capsules containing a water-insoluble drug. An immediate release hydrochlorothiazide (HCTZ) capsule formulations containing drug, lactose, starch 1500 were prepared and exposed to accelerated stability study (40°C/ambient RH, 40°C/60% RH, 40°C/75% RH, and 40°C/90% RH) in a closed dark bottles for 4 weeks. Notable decrease in drug dissolution was observed after the 4 weeks in all humidity conditions as compared with freshly prepared capsules. In an attempt to overcome capsule cross-linking, glycine alone, citric acid alone and both glycine and citric acid were added to the prepared formulations. In all humidity conditions, addition of glycine alone or citric acid alone did not affect the decrease in dissolution profile. On the other hand, addition of both glycine and citric acid together was found to prevent capsule cross-linking completely. Fourier transfer infra-red (FTIR) spectroscopy and differential scanning calorimetry (DSC) were performed on blank capsules and after storage for 4 weeks to identify the physicochemical changes in drug and other capsule components hence its effect on dissolution.