a Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy , Zagazig University , Zagazig , Egypt.
b Department of Pharmaceutics, College of Pharmacy , Hail University , Hail , Kingdom of Saudi Arabia.
Drug Dev Ind Pharm. 2018 Jun;44(6):873-885. doi: 10.1080/03639045.2017.1417421. Epub 2017 Dec 28.
The aim of the study was to design a self-emulsifying drug delivery system (SEDDS) of the anti-hypertensive Carvedilol in liquid and liquisolid forms as a way to enhance its dissolution profile and anti-hypertensive effect.
Solubility studies of Carvedilol in various oils, surfactants and co-surfactants were conducted, followed by the construction of pseudo-ternary phase diagrams and other in vitro assessments. The selected SEDDS formulation (S1) was adsorbed onto solid powder excipients and compressed into tablets. The resulting liquisolid tablets were evaluated under British Pharmacopoeia (B.P.) specifications. Pre- and post-compression studies were performed to determine the flow properties and evaluate the liquisolid systems, followed by in vivo studies in hypertensive rats.
Attempts of self-emulsification, droplet size, and thermodynamic stability studies showed acceptable results for the S1 formulation containing Capryol 90, Tween 20, and Transcutol HP (10:53.3:26.2%), respectively. Pre-compression studies showed adequate flowability and compatibility of liquid and solid excipients with Carvedilol. The selected liquisolid tablet (LS7) demonstrated the best disintegration and water absorption ratio in addition to satisfactory friability and hardness. A significantly (p < .05) fast dissolution rate was observed for both SEDDS and liquisolid formulations when compared to pure drug and marketed Carvepress. The in vivo study of LS7 formulation revealed a rapid significant (p < .01) decrease in the mean arterial pressure (MAP) of the rats (112.72 mmHg) within the first 30 min followed by a further decline (107.22 mmHg) after 1 h when compared to Carvepress.
Self-emulsifying liquisolid tablets expressed rapid onset of action with enhanced anti-hypertensive effect of Carvedilol.
本研究旨在设计一种液体和液固形式的抗高血压药物卡维地洛自乳化给药系统（SEDDS），以提高其溶解特性和抗高血压效果。
对卡维地洛在各种油、表面活性剂和助表面活性剂中的溶解度进行了研究，随后构建了伪三元相图和其他体外评估。选择SEDDS 配方（S1）吸附在固体粉末赋形剂上并压制成片剂。根据英国药典（B.P.）的规格对所得液固体制剂进行评估。进行了预压缩和后压缩研究，以确定流变性并评估液固体制剂，随后在高血压大鼠中进行体内研究。
自乳化尝试、液滴大小和热力学稳定性研究表明，含有 Capryol 90、Tween 20 和 Transcutol HP（10:53.3:26.2%）的 S1 配方具有可接受的结果。预压缩研究表明，液体和固体赋形剂与卡维地洛具有足够的流变性和相容性。所选液固体制剂（LS7）在除了令人满意的脆性和硬度外，还表现出最佳的崩解和吸水率。SEDDS 和液固体制剂的溶解速率均明显（p<0.05）快于纯药物和市售 Carvepress。LS7 制剂的体内研究表明，与 Carvepress 相比，大鼠的平均动脉压（MAP）在最初 30 分钟内迅速显著（p<0.01）下降（112.72mmHg），1 小时后进一步下降（107.22mmHg）。
自乳化液固体制剂表现出卡维地洛快速起效的作用，增强了抗高血压效果。
