A randomized two-way crossover comparative pharmacokinetic study of two different tablet formulations containing ilaprazole in healthy human Indian volunteers

Abstract

Background: Proton Pump Inhibitors (PPI) are observed to be great healer in gastroesophageal reflux disorder (GERD) and duodenal ulcer. Quantification of the drugs in human plasma by validated bioanalytical method are very important to determine pharmacokinetic parameters for undergoing comparative study with standard available formulations to make the newer one commercially available. Objective: The objective of this study was to determine the relative bioavailability of Ilaprazole, a novel PPI comparing the test formulation to the reference one according to standard regulatory guidelines. Materials and Methods: The bioequivalence of two tablet formulations, one as reference and other as test containing 10 mg of ilaprazole [CAS No. 172152-36-2] was studied in 12 healthy Indian volunteers. This was a single dose, twoperiod and randomized crossover study separated with a washout period of one week. Plasma samples for pharmacokinetic analysis were collected before dosing and at pre-specified time points after dosing. The concentration of ilaprazole in plasma was determined by a validated HPLC-UV method using theophylline as internal standard. The formulations were compared using the parameters Area under the plasma concentration-time curve (AUC 0-t ), Area under the plasma concentration-time curve from zero to infinity (AUC 0-͵), Peak plasma concentration (C max ), and time to reach peak plasma concentration (t max ). Results: Mean AUC 0-t of test and reference product were calculated to be 2627.793 ± 154.989 ng h ml−1 and 2555.905 ± 225.916 ng h ml−1 , with a C max of 347.459 ± 48.175 ng h ml−1 . While mean AUC 0-͵ of test and reference product were calculated to be 2733.334 ± 242.438 ng h ml−1 and 2728.716 ± 284.408 ng h ml−1 . Conclusion: The results of this investigation indicated no statistically significant differences between the logarithmic transformed AUC 0-͵ and C max values of the two preparations. The 90% confidence interval for the ratio of the logarithmic transformed AUC 0-t , AUC 0-͵ and C max were 2 within the bioequivalence limit of 80-125% and the relative bioavailability of test formulation was 102.81% to that of reference formulation. The results of this study in healthy human volunteers of 27.92 ± 5.12 yrs (average age), 171.28 ± 6.85 cm (average height) and 66.43 ± 5.21 kg (average weight) support the use of the 10 mg dose tablet newly formulated.