Liquisolid technique as a new approach to sustain propranolol hydrochloride release from tablet matrices

Abstract

It is suggested here that liquisolid technique has the potential to be optimized for the reduction of drug dissolution rate and thereby production of sustained release systems. In the present study, propranolol hydrochloride was dispersed in polysorbate 80 as the liquid vehicle. Then a binary mixture of carrier-coating materials (Eudragit RL or RS as the carrier and silica as the coating material) was added to the liquid medication under continuous mixing in a mortar. The final mixture was compressed using the manual tableting machine. The effect of drug concentration, loading factor, thermal treating and aging on release profile of propranolol hydrochloride from liquisolid compacts were investigated at two pH values (1.2 and 6.8). The release rate of propranolol HCl from liquisolid compacts was compared to the release of propranolol HCl from conventional tablets. X-ray crystallography and DSC were used to investigate the formation of any complex between drug and excipients or any crystallinity changes during the manufacturing process. Propranolol HCl tablets prepared by liquisolid technique showed greater retardation properties in comparison with conventional matrix tablets. This investigation provided evidence that polysorbate 80 (Tween 80) has important role in sustaining the release of drug from liquisolid matrices, and a reduction of Tg of the polymer can be the reason for the release prolongation of liquisolid tablets. The results also showed that wet granulation had remarkable impact on release rate of propranolol HCl from liquisolid compacts, reducing the release rate of drug from liquisolid compacts. The results showed that aging (liquisolid tablets were kept at 25 آ°C/75% relative humidity for 6 months) had no effect on hardness and dissolution profile of drug. The kinetics studies revealed that most of the liquisolid formulations followed the zero-order release pattern. X-ray crystallography and DSC ruled out any changes in crystallinity or complex formation during the manufacturing process of liquisolid formulations. é 2008 Elsevier B.V. All rights reserved.