Carvedilol nano lipid carriers: formulation, characterization and in-vivo evaluation

Abstract

The purpose of this study was to develop Carvedilol nanostructured lipid carriers (CAR-NLCs) using stearic acid and oleic acid as lipid, and to estimate the potential as oral delivery system for poorly water soluble drug. The particle-size analysis revealed that all the developed formulations were within the nanometer range. The EE and loading were found to be between 69.45-88.56% and 9.58-12.56%, respectively. The CAR-NLCopt showed spherical morphology with smooth surface under transmission electron microscope (TEM). The crystallization of the drug in NLC was investigated by powder X-ray diffraction and differential scanning calorimetry (DSC) and revealed that the drug was in an amorphous state in the NLC matrix. The ex vivo gut permeation study showed many folds increment in the permeation of CAR-NLCs compared to Carvedilol suspension (CAR-S). The oral bioavailability study of CAR was carried out using Wistar rats and relative bioavailability of CAR-NLCopt was found to be 3.95 fold increased in comparison with CAR-S. In vivo antihypertensive study in Wistar rats showed significant reduction in mean systolic BP by CAR-NLCopt vis-à-vis CAR-S (p50.05) owing to the drug absorption through lymphatic pathways. In conclusion, the NLC formulation remarkably improved the oral bioavailability of CAR and demonstrated a promising perspective for oral delivery of poorly water-soluble drugs. The promising findings in this investigation suggest the practicability of these systems for the enhancement of bioavailability of CAR.

Preparation and evaluation of carvedilol-loaded solid lipid nanoparticles for targeted drug delivery

“…This peak was not evident in the thermograms of the SLN formulations indicating that CL was not in the crystalline state, but rather present in amorphous state with the drug completely entrapped within the solid lipid [6].…”

“…The slow release of CL is an indication that the active agent was at the core and surrounded by the lipid. Due to the increased diffusional distance the drug would normally have sustained release [6,22]. According to highest k and r 2 values and according to lowest AIC values from DDsolver programme, in vitro release of CL from formulations followed first order and Higuchi models showing the controlled release property of formulation.…”

“…The oral bioavailability remains low because of significant first-pass hepatic metabolism by cytochrome P450 and also because of its short plasma halflife [6]. Long-term therapy of cardiovascular diseases by orally administered CL may result in poor patient compliance because of low bioavailability.…”

“…Lipid particles are of great importance to drug researchers and developers because of their ability to avoid hepatic first pass metabolism and because they enhance intestinal permeability [6,7].…”

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“…Remarkably improved the oral bioavailability [68] SEPS: Solvent emulsification evaporation-probe sonication, HPH: High-pressure homogenization plain drug suspension. These results showed the potential of NLCs for significant improvement in oral BA of poorly soluble RLX.…”