Department of Pharmaceutics, Jangaon Institute of Pharmaceutical Sciences, Jangaon, Warangal, Telangana 506167, India.
Vaagdevi College of Pharmacy, Warangal, Telangana State 506005, India.
Pharm Nanotechnol. 2020;8(3):207-224. doi: 10.2174/2211738508666200517121637.
Carvedilol (CD), a non-selective beta-blocker, is indicated for the management of mild to moderate congestive heart failure. After oral administration, CD is rapidly absorbed with an absolute bioavailability of 18-25% because of low solubility and extensive first-pass metabolism.
The present investigation focused on enhanced oral delivery of CD using supersaturated self-emulsifying drug delivery (SEDDS) system.
Optimized SEDDS consisted of a blend of Oleic acid and Labrafil-M2125 as an oil-phase, Cremophor-RH40, polyethylene glycol-400 and HPMC-E5 as a surfactant, co-surfactant and supersaturation promoter respectively. Formulations were characterized for physical characteristics, invitro release in simulated and biorelevant dissolution media, intestinal permeability and bioavailability studies in Wistar rats. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis, scanning electron microscopy (SEM) studies were used to confirm the crystalline nature and shape of the optimized formulation.
DSC and XRD, SEM studies showed that the drug was in amorphous form, and droplets were spherical in shape. Dissolution studies clearly showed distinct CD release in compendial and biorelevant dissolution media. The results from permeability and in-vivo studies depicted 2.2-folds and 3.2-folds increase in permeability and bioavailability, respectively from supersaturated SEDDS in comparison with control.
The results conclusively confirmed that the SEDDS formulation could be considered as a new alternative delivery vehicle for the oral supply of CD. Lay Summary: Carvedilol (CD) is a non-selective antihypertensive drug with poor oral bioavailability. Previously, various lipid delivery systems were reported with enhanced oral delivery. We developed suprsaturable SEDDS formulation with immediate onset of action. SEDDS formulation was developed and optimized as per the established protocols. The optimized SEDDS formulation was stable over three months and converted to solid and supersaturated SEDDS. The results from permeability and in-vivo studies demonstrated an enhancement in permeability and bioavailability from supersaturated SEDDS in comparison with control. The results conclusively confirmed that the SEDDS formulation could be considered as a new alternative delivery vehicle for the oral administration of CD.
卡维地洛（CD）是一种非选择性的β受体阻滞剂，适用于轻度至中度充血性心力衰竭的治疗。口服给药后，由于低溶解度和广泛的首过代谢，CD 迅速吸收，绝对生物利用度为 18-25%。
本研究旨在通过超饱和自乳化药物传递系统（SEDDS）提高 CD 的口服递送。
优化的 SEDDS 由油酸和 Labrafil-M2125 作为油相、Cremophor-RH40、聚乙二醇-400 和 HPMC-E5 作为表面活性剂、助表面活性剂和增溶剂分别组成。对制剂的物理特性、模拟和生物相关溶解介质中的体外释放、Wistar 大鼠的肠通透性和生物利用度进行了表征。差示扫描量热法（DSC）和 X 射线衍射（XRD）分析、扫描电子显微镜（SEM）研究用于确认优化配方的结晶性质和形状。
DSC 和 XRD、SEM 研究表明，药物呈无定形状态，液滴呈球形。溶解研究清楚地表明，在典规定义的溶解介质和生物相关溶解介质中，CD 有明显的释放。通透性和体内研究的结果表明，与对照相比，超饱和 SEDDS 使通透性和生物利用度分别增加了 2.2 倍和 3.2 倍。
结果证实，SEDDS 制剂可被视为 CD 口服供应的新替代传递载体。
