The effects of aging on the dissolution of phenytoin sodium capsule formulations

The effects of formulation and storage conditions on the dissolution of sodium phenytoin capsules have been evaluated. Capsule formulations were prepared containing lactose or CaSO₄ · 2H₂O as the excipient at a low (1:1) and high (3:1) excipient to drug ratio. The capsules were stored for 2 or 8 weeks at 11% and 67% relative humidity. The dissolution data were analyzed using a non-linear least-squares regression program and the Weibull function. An analysis of variance (ANOVA) performed on each of the Weibull function parameters revealed that the formulation and storage conditions had different effects on each of these parameters. A specific interaction between CaSO₄ · 2H₄O and phenytoin sodium was not evident from the data; however, significant effects on the deaggregation process could be detected from changes in the β parameter. Several interaction effects between storage conditions and formulation factors were also evident from the ANOVA results. This study illustrates the utility of the Weibull function analysis of dissolution data for detecting drug-excipient interactions and storage-related changes in solid dosage forms.