Effect of particle size on oral absorption of carvedilol nanosuspensions: in vitro and in vivo evaluation

Abstract

The purpose of this work was to explore the particle size reduction effect of carvedilol on dissolution and absorption. Three suspensions containing different sized particles were prepared by antisolvent precipitation method or in combination with an ultrasonication process. The suspensions were characterized for particle size, surface morphology, and crystalline state. The crystalline form of carvedilol was changed into amorphous form after antisolvent precipitation. The dissolution rate of carvedilol was significantly accelerated by a reduction in particle size. The intestinal absorption of carvedilol nanosuspensions was greatly improved in comparison with microsuspensions and solution in the in situ single-pass perfusion experiment. The in vivo evaluation demonstrated that carvedilol nanosuspensions and microsuspensions exhibited markedly increased C max (2.09- and 1.48-fold) and AUC 0− t (2.11- and 1.51-fold), and decreased T max (0.34- and 0.48-fold) in contrast with carvedilol coarse suspensions. Moreover, carvedilol nanosuspensions showed good biocompatibility with the rat gastric mucosa in in vivo gastrointestinal irritation test. The entire results implicated that the dissolution rate and the oral absorption of carvedilol were significantly affected by the particle size. Particle size reduction to form nanosized particles was found to be an efficient method for improving the oral bioavailability of carvedilol.

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

“…The results obtained from DSC and PXRD combined, show that carvedilol lyophillized formulations were in the amorphous state. Numerous diffraction peaks of carvedilol were observed at 2θ of 12.4°, 24.4° and 26.1°, and this reveals the crystalline nature of carvedilol [1,18,19].…”

“…Usually, a small value of PDI indicates a homogenous population, while a larger PDI means a high heterogeneity in particle size [21]. Pure carvedilol had an irregular shape, while the lipid Dynasan shape was cluster-like, and the CL-SLN (F3) exhibited a flaky shape [18].…”

“…The results showed that the particles were flakes with a narrow size distribution, and had smooth surfaces. Particle size results and SEM images pointed out that particles were different not only in size, but also in shape., Carvedilol pure powders had a non-uniform shape, while SLN formulations had a flaky shape [18,19].…”

Understanding peroral absorption: regulatory aspects and contemporary approaches to tackling solubility and permeability hurdles

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“…Particle Size Distribution and Zeta potential Analysis: 33 Particle size, size distribution and zeta potential of diacerein nanosuspension were determined using Zetatrac (Microtrac Inc., USA). Zetatrac utilizes a high-frequency AC electric field to oscillate the charged particles.…”