الفهرس 
Aim of workOnly 14 pages are availabe for public view
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Abstract
The aim of this study is to develop carvedilol cubosomes (CARV-CUBs) and apply a comparative analysis of cremophor RH 40 and polyvinyl alcohol as secondary stabilizers for enhancing oral CARV bioavailability and prolonging its action in the treatment of hypertension. D-optimal design was applied to find the most significant factors affecting CARV-CUBs properties. The studied variables were Poloxamer 407 content (P407%), secondary stabilizer concentration, and type of secondary stabilizer. Particle size (PS), polydispersity index (PDI), CARV content, and zeta potential (ZP) were chosen as dependent responses. Two optimum formulations were selected based on the desirability factor (0.762 and 0.639) for PVA-based CUBs and RH 40-based CUBs, respectively. The optimized formulations showed PS of 141 ± 1 nm, and 105 ± 0 nm, PDI of 0.166 ± 0.00 and 0.247 ± 0.01, ZP of 4.9 ± 0.3 mV and 6.3 ± 0.3 and CARV content of 105.0 ± 1.4 % and 93.6 ± 0.9 % for PVA-based CUBs and RH 40-based CUBs, respectively. Transmission electron microscope (TEM) imaging confirmed the characteristic cubic morphology of the prepared CUBs. Differential Scanning Calorimetry (DSC) analysis of the CARV-CUBs suggested the transformation of CARV crystal into an amorphous state. Moreover, the prepared CARV-CUBs exhibited an in-vitro sustained release behavior and comparable in-vivo antihypertensive activity.
Keywords: Carvedilol, liquid crystalline nanoparticles, cubosomes, stabilizers effect, optimization, antihypertensive activity.