Design of lamivudine XR matrix tablets: Influence of HPMC and PEO on in vitro drug release and bioavailability in rabbits

Abstract

Background/objectives

In the present study oral extended release matrix tablets of lamivudine were formulated, characterized and evaluated for in vitro dissolution and in vivo bioavailability performance in rabbits.

Methods

Matrix tablets of lamivudine were prepared using hydroxypropyl methylcellulose K100M and its combination with polyethylene oxide as the release rate retardant polymers. The tablets were characterized for physical properties, moisture uptake studies, in vitro dissolution, accelerated stability (40 ± 2 °C and 75 ± 5% RH) testing. In vivo studies were performed by oral administration of optimized formulation in rabbits.

Results

In vitro studies revealed that the release rate decreased with increase in polymer concentration, polymer viscosity and combination of polymers. The drug release from the matrix tablets followed diffusion mechanism. Comparable correlation of in vitro drug release was observed in the initial and accelerated stability samples of lamivudine matrix tablets prepared with hydroxypropyl methylcellulose alone and its combination with polyethylene oxide. Significant bioavailability was observed in the in vivo evaluation. The C_max, t_max, AUC and K_el for F-3 matrix tablets were 1361 ng/ml, 4 h, 25,013.5 ng min/ml and 0.0719 h⁻¹ respectively. DSC and FT-IR spectra of initial and stability samples showed the absence of drug–excipient incompatibility in the formulations. The developed extended release matrix tablets of lamivudine were stable up to three months.

Conclusions

The release of the matrix tablets for prolonged periods of time employing polyethylene oxide and hydroxypropyl methylcellulose as drug rate retarding polymers could be advantageous than conventional lamivudine tablets. The study could be extended for bioavailability studies in clinical subjects.