Javadzadeh Yousef, Musaalrezaei Leila, Nokhodchi Ali
Faculty of Pharmacy and Drug Applied Research Centre, Tabriz University of Medical Sciences, Tabriz 51664, Iran.
Int J Pharm. 2008 Oct 1;362(1-2):102-8. doi: 10.1016/j.ijpharm.2008.06.022. Epub 2008 Jul 4.
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 T(g) 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 degrees 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.
本文提出液固技术有潜力通过优化来降低药物溶解速率,从而制备缓释系统。在本研究中,盐酸普萘洛尔分散于聚山梨酯80中作为液体载体。然后在研钵中持续搅拌的情况下,将二元载体 - 包衣材料混合物(以尤特奇RL或RS为载体,二氧化硅为包衣材料)加入到液体制剂中。最终混合物使用手动压片机进行压制。在两个pH值(1.2和6.8)下,研究了药物浓度、载药量、热处理和老化对盐酸普萘洛尔液固型片剂释放曲线的影响。将盐酸普萘洛尔液固型片剂的释放速率与传统片剂中盐酸普萘洛尔的释放进行了比较。采用X射线晶体学和差示扫描量热法研究了药物与辅料之间是否形成任何复合物,以及在制造过程中是否有任何结晶度变化。与传统骨架片相比,采用液固技术制备的盐酸普萘洛尔片剂显示出更大的缓释性能。该研究提供了证据表明聚山梨酯80(吐温80)在维持液固型基质中药物释放方面具有重要作用,聚合物玻璃化转变温度(Tg)的降低可能是液固型片剂释放延长的原因。结果还表明,湿法制粒对盐酸普萘洛尔液固型片剂的释放速率有显著影响,降低了药物从液固型片剂中的释放速率。结果表明,老化(液固型片剂在25℃/75%相对湿度下保存6个月)对药物的硬度和溶出曲线没有影响。动力学研究表明,大多数液固型制剂遵循零级释放模式。X射线晶体学和差示扫描量热法排除了液固型制剂制造过程中结晶度或复合物形成的任何变化。