Development and In Vitro and In Vivo Evaluation of Microspheres Containing Sodium <i>N</i>-[8-(2-hydroxybenzoyl)amino]caprylate for the Oral Delivery of Berberine Hydrochloride

Abstract

Microspheres containing absorption enhancer (sodium N-[8-(2-hydroxybenzoyl)amino]caprylate, SNAC) were developed to enhance the oral bioavailability of berberine hydrochloride (BER) with poor intestinal membrane permeability. Microspheres were prepared and characterized by particle size measurements, scanning electron microscopy, differential scanning calorimetry, BER payload and release, Caco-2 cell monolayer transport, and rat pharmacokinetics. The microspheres were spherical and had uniform size, high encapsulation efficiency and high loading capacity. In vitro release studies showed that BER-loaded microspheres had good sustained release characteristics. The Caco-2 cell monolayer transport study proved that SNAC could significantly enhance permeability of BER 2–3-fold. Pharmacokinetic studies demonstrated a 9.87-fold increase in area under the curve (AUC) of BER mixed with SNAC and a 14.14-fold increase in AUC of microspheres compared with BER alone. These findings indicate that SNAC is a promising absorption enhancer for oral delivery of BER in the form of both solution and microspheres.

Keywords

• sodium <i>N</i>-[8-(2-hydroxybenzoyl)amino]caprylate
• permeation enhancement
• berberine hydrochloride
• microspheres
• oral bioavailability