Lipid-based floating multiparticulate delivery system for bioavailability enhancement of berberine hydrochloride

ABSTRACT

The objective of the present investigation was to design and optimize lipid-based floating multiparticulate of Berberinehydrochloride (BERH), so as to increase its solubility and to reduce P-Glycoprotein mediated efflux in the intestine,hence to improve oral bioavailability. Solid dispersions were prepared using hydrophilic carriers gelucire 44/14and gelucire 50/13 in different ratio. The prepared solid dispersion of BERH was further formulated into sustainrelease gastroretentive floating pellets using hydrophobic lipid carrier gelucire 43/01 as release retardant, sodiumbicarbonate (NaHCO3) and hydroxylpropyl methyl cellulose K4M (HPMC K4M) as gas former and matrix polymer,respectively. The effect of amount of gelucire 43/01 and NaHCO3 HPMC K4M were studied and optimized using a3-level, 2-factor, factorial design. Solid dispersion of BERH compared to pure drug showed 4-fold enhancement inaqueous solubility. The optimum system could float for more than 8 hours and showed 88.46% drug release in 8 hours.The pharmacokinetic study conducted in male Wistar rats indicated 2.32-fold increase in relative bioavailability ofoptimized formulation compare to the marketed tablet. The lipid-based floating pellets of BERH were obtained andcould be an applicable choice to deliver BERH with improved bioavailability in effective use for various clinicalapplications.