Development of self-microemulsifying drug delivery system for oral bioavailability enhancement of berberine hydrochloride

Abstract

The purpose of this study was to develop a self-microemulsifying drug delivery system (SMEDDS) to improve the oral bioavailability of Berberine hydrochloride (BBH), an important bioactive compound from Chinese Medicines with poor water solubility. Pseudoternary phase diagrams were constructed using oil, surfactant and co-surfactant types to identify the efficient self-microemulsification region. SMEDDS was characterized by morphological observation, droplet size, zeta-potential determination, stability, in vitro release and in vivo bioavailability study. The optimal formulation with the best self-microemulsifying and solubilization ability consisted of 40% (w/w) of ethyl linoleate and oleic acid (2:1), 35% (w/w) Tween-80 and 25% (w/w) glycerol. The SMEDDS of BBH could exhibit good stability. In vitro release test showed a complete release of BBH from SMEDDS was in 5 h. In vivo results indicated that the peak plasma concentration (C(max)) and the area under the curve (AUC(0→12 h)) of SMEDDS of BBH were higher than the commercial tablet by 163.4% and 154.2%, respectively. The relative bioavailability of SMEDDS of BBH was enhanced about 2.42-fold compared with the commercial tablet in rats. The study confirmed that the SMEDDS formulation could be used as a possible alternative to traditional oral formulations of BBH to improve its bioavailability.

Self-nanoemulsifying drug delivery systems ameliorate the oral delivery of silymarin in rats with Roux-en-Y gastric bypass surgery

“…These ions minimize the surface charge of nanoemulsions generated from self-emulsifying systems. 18 This is the reason that SGF shielded the negative charge of SNEDDS. The zeta potential of near 0 results in insufficient repulsion between droplets and subsequent aggregation, confirming the larger droplets in SGF as compared with water.…”

“…The complete solubilization by PEG 400 and SNEDDS suggested that the mechanism for the improvement in bioavailability brought about by the nanocarriers involved not only the dissolution rate. PEG 400 has strongly hydrophilic characteristics, 18 leading to difficulty with regard to partitioning into the lipophilic GI membrane. When dissolved in oil droplets, the drug can be absorbed directly by the membrane via fusion or interaction.…”

Controversies with self-emulsifying drug delivery system from pharmacokinetic point of view

“…Most of the articles on SMEDDS or SNEDDS highlighted the nano-scale dispersion as one of the major contributing factors behind improved drug absorption after oral administration compared to either normal solution or suspension (Zhu et al, 2013;. However, comparative in vivo studies with variable droplet size with the same SEDDS have been rarely reported.…”

Development and evaluation of vitamin E D-α-tocopheryl polyethylene glycol 1000 succinate-mixed polymeric phospholipid micelles of berberine as an anticancer nanopharmaceutical

“…The retention time of Brb was ~7 minutes, and the encapsulation efficiency (EE%) of Brb in the Mic samples was calculated based on standard curves constructed in the range of 4-200 μg/mL (r 2 =0.998, n=3), which were validated for linearity, precision, and accuracy. 7,8,16 Physical stability of Brb-micelles…”

“…[2][3][4]9,12,18,21 Recently, several nanoparticulate delivery systems for Brb have been reported, attempting to address the major pharmaceutical concerns associated with its systemic administration, with lipid-based nanocarriers being the most investigated. 1,[6][7][8]12,16 Currently, lipopolymeric micelles are popular pharmaceutical delivery vehicles for poorly water-soluble active compounds, such as Brb, which can be solubilized within the hydrophobic core of a micelle. Micelles prepared from conjugates of polyethylene glycol (PEG) and diacyllipids, such as phosphatidylethanolamine (PE) -ie, PEG-PE conjugates -have demonstrated several pharmaceutical advantages such as small size (10-100 nm), good solubilization efficacy, low toxicity, controlled drug release, and extremely high stability due to very low critical micelles concentration (CMC) (typically in the micromolar range).…”