Bioavailability enhancement of nanostructured microparticles of carvedilol

A high throughput encapsulation technique termed as electrospraying assisted by pressurized gas technology (EAPG) was used to produce nano-within-micro structures of a Biopharmaceutics Classification System (BCS) Class II model drug. Carvedilol is a lipid soluble compound, poorly absorbed in the gastrointestinal tract. The produced formulations were characterized in terms of morphology, crystallinity, in vitro dissolution test, in vitro Caco-2 cells permeability and in vivo pharmacokinetics in rats. Spherical microparticles with a carvedilol loading of 80% were produced with sizes around 4 μm.

Highlights

Nanostructured microparticles of carvedilol were produced via EAPG technology.

4 μm spherical microparticles with a carvedilol loading of 80% were formulated.

Carvedilol nanoparticles of controlled size were dispersed within the microparticles.

The microparticles dissolved 4-fold faster than the commercial carvedilol in 30 min.

Apparent permeability in Caco-2 cells was 2.5-fold higher than that of the control.

DLS and TEM suggested that carvedilol is released in the form of nanoparticles of controlled size when the microparticles are put in solution, and WAXS and DSC confirmed that carvedilol was in an amorphous state. In vitro dissolution tests showed that the produced microparticles dissolved 4-fold faster than the commercial carvedilol in the first 30 min. The apparent permeability in Caco-2 cells of the produced formulations was approximately 2.5-fold higher than the apparent permeability of the commercial carvedilol.

The preliminary pharmacokinetic assay suggested a reduction in 2 h of the C_max for the prepared formulations, but due to the high variability observed, the results need to be confirmed in further studies. This work showed the potential of nanostructured microparticles of an API via EAPG to increase dissolution rate and hence the bioavailability of a BCS Class II drug.

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Article information: C. Prieto, Z. Evtoski, M. Pardo-Figuerez, J.M. Lagaron, Bioavailability enhancement of nanostructured microparticles of carvedilol, Journal of Drug Delivery Science and Technology, 2021. https://doi.org/10.1016/j.jddst.2021.102780.