Predictive ability of level A in vitro-in vivo correlation for ringcap controlled-release acetaminophen tablets.

PURPOSE: The goal of this study was to establish and validate an in vitro-in vivo correlation (IVIVC) for two sustained-release formulations (i.e., a matrix tablet and a RingCap banded matrix tablet) containing 750 mg of acetaminophen. METHODS: The in vitro dissolution and in vivo disposition of these formulations were examined by using a USP type III dissolution apparatus and a single-dose, three-way, crossover study that included an immediate-release acetaminophen dosage form, respectively. An IVIVC was established by using the mean fraction dissolved (FD) and mean fraction absorbed (FA) and used to simulate the plasma concentration-time profile of acetaminophen after administration of the matrix tablet (i.e., internal validation) and RingCap banded matrix tablet (i.e., external validation). RESULTS: A statistically significant relationship (r2 = 0.997, P < 0.001) existed between the FD and FA for matrix tablets and was best described by the equation (FA) = 0.984 x (FD) + 0.0133. The percent predictions errors in CMAX and AUCL were <10% when predicting the plasma concentration-time profiles for the two formulations, validating the internal and external predictability of the IVIVC. CONCLUSIONS: The data (i) show that in vitro dissolution data are a good predictor of in vivo fraction absorbed for acetaminophen, (ii) support the general use of in vitro dissolution data for readily soluble and readily absorbed drugs, (iii) suggest that acetaminophen may serve as a model drug for evaluating novel sustained-release delivery systems, and (iv) provide a tangible example of the limitations of current methods for predicting and validating IVIVC.

Water vapor sorption of water-soluble substances: studies of crystalline solids below their critical relative humidities.

Water vapor sorption on unground and ground samples of sodium chloride and sodium salicylate at relative humidities below RHo, that at which deliquescence is initiated, has been measured. Sorption isotherms, expressed as the amount sorbed per unit area of solid surface, were different for unground and ground samples. Measurement of specific surface area for samples previously exposed to various relative humidities revealed no change with unground samples but a significant reduction with ground samples beyond about 20% relative humidity. Correcting isotherms for this change in area brings the results with ground and unground samples into closer agreement. These studies reveal that relatively low levels of water vapor sorption on crystalline water-soluble solids, below RHo, can give rise to some form of "surface dissolution" when the solid had been subjected to various forms of mechanical disturbance.