Precise Dissolution Control and Bioavailability Evaluation for Insoluble Drug Berberine via a Polymeric Particle Prepared Using Supercritical CO2

Abstract

It is still controversial whether poor aqueous solubility is the most primary reason for the low oral bioavailability of insoluble drugs. Therefore, in this study, berberine-loaded solid polymeric particles (BPs) of varied dissolution profiles with β-cyclodextrin (β-CD) as carrier were fabricated using solution-enhanced dispersion by supercritical fluids (SEDS), and the relationship between dissolution and berberine (BBR) bioavailability was evaluated. Dissolution property was controlled via particle morphology manipulation, which was achieved by adjusting several key operating parameters during the SEDS process. Characterization on BP using infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction indicated that BBR was dispersed in amorphous form, while nuclear magnetic resonance spectroscopy showed that methoxy groups of BBR were included into the cavities of β-CD. In vivo pharmacokinetic studies showed that oral bioavailability increased by about 54% and 86% when the dissolution rate of BBR was increased by 51% and 83%, respectively. The entry speed of BBR into the bloodstream was also advanced with the degree of dissolution enhancement. It seemed that dissolution enhancement gave positive effect to the oral bioavailability of berberine, but this might not be the crucial point. Meanwhile, supercritical CO2 technology is a promising method for pharmaceutical research due to its advantages in regulating drug-dosage properties.

Supercritical Fluid Processing of Polymers

“…In conclusion, the articles published in this special issue, and reported above, confirmed the interesting peculiarities of supercritical fluids, i.e., SC-CO 2, that allow to improve the traditional processes performance [1,2,3,9] and the characteristics of a large number of polymers [4,5,6,7,8].…”

“…This special issue currently consists of a total of nine articles written by research groups of experts in the field. The papers can be substantially divided into two main topics:polymeric structure (nanoparticles, microparticles, foams) formation [1,2,3], useful for drug release applications;effects of supercritical fluids on polymer characteristics [4,5,6,7,8]. …”

“…polymeric structure (nanoparticles, microparticles, foams) formation [1,2,3], useful for drug release applications;…”

“…Regarding the polymeric structure formation, in the study of Jia et al [1], berberine-loaded solid polymeric particles (BPs) with β-cyclodextrin (β-CD) were generated using a solution-enhanced dispersion process assisted by supercritical fluids (SEDS). Moreover, the relationship between dissolution and berberine (BBR) bioavailability was evaluated.…”

“…In particular, an innovative SC-CO 2 assisted electrospray process has been proposed for the first time [2], showing promising results in terms of polymeric particles generation, and two different SC-CO 2 assisted techniques (SEDS and SC-foaming) for the generation of polymeric drug-loaded devices have shown interesting results in terms of drug controlled release [1,3], i.e., modifying the processes parameters it is possible to control the specific drug release. Moreover, SC-CO 2 confirmed the capability of improving the mechanical characteristics of several polymers (i.e., polymeric fibers) at specific operating conditions [4,5,6,7,8].…”