Comparative bioavailability and in vitro in vivo correlation of two sustained release brands of theophylline: tablets and pellets

ABSTRACT

To investigate the influence of dosage forms on bioavailability, a randomized single-dose crossover study under fasting conditions was conducted using two commercially available sustained release products, Quibron SR tablets and Respro-SR pellets filled Capsules containing 300mg theophylline. A group of 12 healthy, male human subjects participated in this study. Serial blood samples were collected at 0, 1, 2, 3, 4, 6, 8, 10, 12 and 24 h. Theophylline was measured by high-performance liquid chromatography while absorption profiles were derived using Wagner-Nelson equation. The bioavailability of Quibron SR tablets was compared with Respro-SR pellets filled Capsules 300 mg using pharmacokinetic parameters C[max], T[max], AUC0-t, and AUC0-8. In addition, the 90% confidence interval [CI] for the ratio of logarithmic transformed C[max] and AUC0-8 was also used to determine bioequivalence. The T/R [test/reference] ratio of Quibron SR tablets was quite close to the prescribed limits of bioequivalence i.e. 80-125%. No st atistically difference was observed between the log transformed AUC[0-infinity] [P = 0.971] values as well as log transformed C[max] values [P = 0.854] indicating bio-availability and the extent of absorption of two brands were comparable. Moreover, the value of correlation coefficients for% in vivo absorption versus% in vitro dissolution of the two products was calculated to be 0.9533 for Respro-SR capsule and 0.9789 for Quibron-SR tablets