Development of Bioadhesive Microspheres for Oral Bioavailability Enhancement of Berberine Hydrochloride

Ye Zhang,Hongming Liu

doi:10.1155/2016/4235832

Ye Zhang, Hongming Liu

Open Access

https://doi.org/10.1155/2016/4235832

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Abstract

The objective of this study was to innovatively prepare chitosan-coated alginate/gelatin BBH loaded microspheres and evaluate their pharmaceutical characteristics and pharmacokinetics. The bioadhesive microspheres were prepared using an emulsification technique. Three batches of microspheres were formed and their stability was evaluated. BBH loaded microspheres were almost spherical with shallow elevation on surfaces. The mean particle size of microspheres was 368.2 μm, drug loading was3.59±0.01%, andin situbioadhesion percentage was91.23%±8.2%and they achieved a sustained release with 71.29% for 8 hoursin vitro. Pharmacokinetic studies in rats indicated that the bioavailability of BBH microspheres was enhanced about 1.5-fold as compared with commercial tablets. BBH microspheres exhibited a sustained-release profile over 48 h. Thus, chitosan-coated alginate/gelatin BBH loaded microspheres which combined the advantages of alginate/gelatin microspheres and chitosan may be used as a sustained delivery system for BBH to treat duodenal and benign gastric ulcers.

Highlights

Berberine hydrochloride (BBH), an active isoquinoline alkaloid, is widely present in various traditional Chinese medicines such as Hydrastis canadensis, Coptis chinensis (Coptis or golden thread), Berberis aquifolium (Oregon grape), Berberis vulgaris, and Berberis aristata
BBH, chitosan, gelatin, ethyl-3- (3-dimethylaminopropyl) carbodiimide (EDC), and NHS were obtained from Sigma-Aldrich Co
scanning electron microscopy (SEM) photographs showed that particles of alginate/gelatin BBH loaded microspheres with deep elevation on surfaces were spherical on the whole (Figure 1(a))

Summary

Introduction

Berberine hydrochloride (BBH), an active isoquinoline alkaloid, is widely present in various traditional Chinese medicines such as Hydrastis canadensis (goldenseal), Coptis chinensis (Coptis or golden thread), Berberis aquifolium (Oregon grape), Berberis vulgaris (barberry), and Berberis aristata (tree turmeric). BBH has shown antidepressant activity by modulating brain biogenic amines (norepinephrine, serotonin, and dopamine), oxide pathway, and/or sigma receptors [3,4,5]. BBH has been reported as a novel cholesterol-lowering agent, and it functions through a unique mechanism distinct from statins [6]. BBH, one of the poorly water-soluble drugs and substrate of P-glycoprotein [7, 8], has low mucosal permeability [9], resulting in limited absorption in the gastrointestinal tract, which seriously limits its application and development as a pharmaceutical preparation. Intramuscular and intravenous administration of BBH could result in adverse reactions such as anaphylactic shock and drug eruption [10]. A novel drug delivery system to improve the solubility and bioavailability of BBH has drawn great attention of researchers in pharmaceutical industry

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