Pulsatile core-in-cup valsartan tablet formulations: In vitro evaluation

Abstract

The aim of the present study was to design and evaluate single pulse and floating double pulse valsartan core-in-cup tablets.Core tablets were prepared by direct compression of a homogenous mixture of valsartan, Avicel PH-101, Croscarmellose sodium (CCNa), magnesium stearate & Aerosil. Weight variation, Hardness and Disintegration time were measured for the core tablets.Core-in-cup tablets were formulated using different polymers as a plug layer, including sodium alginate (SA), sodium carboxymethylcellulose (NaCMC) and hydroxypropyl methyl cellulose (HPMC). The floating behavior, water uptake and drug release from the prepared formulations were evaluated. Differential Scanning Calorimetry (DSC) was also performed to detect the possible drug excipient interaction. Stability study of the selected formula was performed at 25 °C & 60% RH and at 40 °C & 75% RH for 3 months. Finally, the existence of the selected formula in the stomach after oral administration to human volunteers was verified via x-ray radiography.The results showed that the release lag time of the tablets increased when the quantity of the plug layer increased thus decreasing the drug release. Plug layer polymers showed a lag time with rank order: SA < NaCMC < HPMC. Selected formulations are F5 & F6. F5 (having SA as the plug polymer) released valsartan after a lag time of 2 h while F6 released the drug in two successive pulses with a reasonable lag time in between due to its floating behavior. Formulations were stable for at least 3 months under standard long-term and accelerated storage conditions.In conclusion, pulsatile single pulse and floating double pulse stable valsartan core-in-cup tablets were successfully formulated which provided a desirable lag time followed by a rapid drug release.