In Vitro and In Vivo Evaluations of Berberine-Loaded Microparticles Filled In-House 3D Printed Hollow Capsular Device for Improved Oral Bioavailability

Abstract

The low oral bioavailability, short biological half-life, high dose, and frequent dosing of berberine (BBR) contribute to its restricted clinical use despite its extensive pharmacological activity. Thus, the objective of this study was to formulate sustained-release microparticles (MPs) using a pH-independent release polymer and to evaluate their potential to improve the oral bioavailability of BBR. BBR loaded MPs were prepared using the emulsion crosslinking method and evaluated for particle size, circularity, morphology, entrapment efficiency, solid-state analysis, swelling index, and in vitro BBR release study fitted with different models of release kinetics. The MPs exhibited desired particle sizes ranges between 11.09–11.62 μm and were almost spherical in shape, as confirmed by the circularity value and micrographic images. A loss of BBR crystallinity was observed after encapsulation in MPs, as evident from various solid-state analyses. The final optimized batch (F3) showed highest % BBR entrapment efficiency value of 81.63% ± 4.9. The in vitro BBR release performance in both acidic and alkaline media showed the desired sustained release behavior from the crosslinked MPs, where the maximum BBR release was observed at alkaline pH, which is in accordance with the swelling study data. In the in vivo study, the oral absorption profiles of BBR from both pristine and MPs formats were investigated using in-house prototyped 3D printed hollow capsules as a unit dose carrier. In vivo data showed sustained and prolonged absorption behavior of BBR from MPs compared to their pristine counterparts, which resulted in a cumulative increment of relative oral bioavailability to mitigate the aforementioned issues related to BBR. Graphical Abstract Supplementary Information The online version contains supplementary material available at 10.1208/s12249-022-02241-9.

Pharmacokinetic of berberine, the main constituent of Berberis vulgaris L.: A comprehensive review

“…Other in vivo and in vitro studies revealed that berberine‐loaded microparticles filled in‐house 3D printed hollow capsular (AUC value: 99.629 ng/ml*h) have higher oral bioavailability in comparison with the pristine berberine (AUC value: 28.629 ng/ml*h); (Choudhury et al, 2022). In rats, using berberine‐loaded liposomes at a dose of 100 mg/kg resulted in even 628% enhancement in the oral bioavailability compared to pure berberine (Duong et al, 2022).…”

“…28.629 ng/ml*h); (Choudhury et al, 2022). In rats, using berberineloaded liposomes at a dose of 100 mg/kg resulted in even 628% enhancement in the oral bioavailability compared to pure berberine (Duong et al, 2022).…”

“…Our intention in this review is to update data and introduce various animal and clinical studies regarding the pharmacokinetic berberine including bioavailability, different metabolism pathways, distribution, excretion, and different drug–drug interactions. Besides, the poor bioavailability of berberine (0.68%) makes restrictions on berberine clinical uses (Chen et al, 2011; Choudhury, Jala, Murty, Borkar, & Banerjee, 2022). Hence, we also gathered and discussed in detail multiple studies regarding the different products of berberine with better pharmacokinetic properties and consequently, better therapeutic and pharmacological effects.…”

“…Our intention in this review is to update data and introduce various animal and clinical studies regarding the pharmacokinetic berberine including bioavailability, different metabolism pathways, distribution, excretion, and different drug-drug interactions. Besides, the poor bioavailability of berberine (0.68%) makes restrictions on berberine clinical uses (Chen et al, 2011;Choudhury, Jala, Murty, Borkar, & Banerjee, 2022).…”

Microspheres and their applications in drug delivery system

“…Synthetic polymer B. Natural polymer  Synthetic polymers  Non-biodegradable polymers: polymethyl methacrylate (PMMA), acrolein, glycidol Methacrylate, epoxy polymer  Biodegradable polymers: lactides, their glycosides and their copolymers, polyalkylenes Cyanoacrylate, polyanhydride  B.Natural polymers It is obtained from different sources such as proteins, carbohydrates and chemically modified products.carbohydrates  Proteins: albumin, gelatin and collagen, carbohydrates: agarose, carrageenan, chitosan, starch, chemicals  .Modified carbohydrates: poly (acrylic acid) dextran, poly (acrylic acid) starch [3].  Particle size and shape: laser microscopy, scanning electron microscopy  Electron spectroscopy for chemical analysis: determination of surface chemistry  Attenuated Total Reflection Fourier Transform Infrared Spectroscopy: Determination of Degradation  Catch rate: % catch = actual content/theoretical content × 100  Thermal Analysis: Differential Scanning Calorimetry (DSC)  Swelling index: Characterization of microspheres using the swelling index technique  METHOD: Take another solution (100ml) such as (distilled water, buffer solution with pH value (1.2,4.5, 7.4) Take alginate microspheres (100mg) and place them in a wire basket.…”