Defining a quantitative and reliable relationship between
in vitro drug release and
in vivo absorption is highly desired for rational development, optimization, and evaluation of controlled-release dosage forms and manufacturing process. During the development of once daily extended-release (ER) tablet of glipizide, a predictive
in vitro drug release method was designed and statistically evaluated using three formulations with varying release rates. In order to establish internally and externally validated level A
in vitro–
in vivo correlation (IVIVC), a total of three different ER formulations of glipizide were used to evaluate a linear IVIVC model based on the
in vitro test method. For internal validation, a single-dose four-way cross over study (
n=6) was performed using fast-, moderate-, and slow-releasing ER formulations and an immediate-release (IR) of glipizide as reference.
In vitro release rate data were obtained for each formulation using the United States Pharmacopeia (USP) apparatus II, paddle stirrer at 50 and 100 rev. min
−1 in 0.1 m hydrochloric acid (HCl) and pH 6.8 phosphate buffer. The
f2 metric (similarity factor) was used to analyze the dissolution data. The formulations were compared using area under the plasma concentration–time curve,
AUC0—∞, time to reach peak plasma concentration,
Tmax, and peak plasma concentration,
Cmax, while correlation was determined between
in vitro release and
in vivo absorption. A linear correlation model was developed using percent absorbed data
versus percent dissolved from the three formulations. Predicted glipizide concentrations were obtained by convolution of the
in vivo absorption rates. Prediction errors were estimated for
Cmax and
AUC0—∞ to determine the validity of the correlation. Apparatus II, pH 6.8 at 100 rev. min
−1 was found to be the most discriminating dissolution method. Linear regression analysis of the mean percentage of dose absorbed
versus the mean percentage of
in vitro release resulted in a significant correlation (
r2≥0.9) for the three formulations.
View full abstract