Investigating permeability related hurdles in oral delivery of 11-keto-β-boswellic acid.

Abstract:

:11-Keto-β-boswellic acid (KBA) is an important and potent boswellic acids responsible for anti-inflammatory action of Boswellia extract. However, its pharmaceutical development has been severely limited by its poor oral bioavailability. The present work aims to investigate the permeability related hurdles in oral delivery of KBA. Gastrointestinal stability, gastrointestinal metabolism, adsorption-desorption kinetics and Caco-2 permeability studies have been carried out. KBA was found poorly permeable with Papp value of 2.85 ± 0.14 × 10(-6)cm/s. Higher absorptive transport indicated role of carrier mediated transport. Moreover, KBA transport across monolayer showed saturation kinetics at higher concentrations. KBA exposed to 1α,25-(OH)2 vitamin D3 treated cell monolayer showed the lowest Papp value of 2.01×10(-6) ± 0.02 × 10(-6)cm/s indicating role of CYP3A4 mediated metabolism during KBA transport. Metabolic stability experiments in jejunum S9 fractions further confirmed this. KBA was found unstable in simulated gastrointestinal fluids and also got accumulated in the enterocytes. Sorption and desorption kinetic studies using Caco-2 cells further confirmed accumulation of KBA inside the enterocytes. KBA also showed pH dependent permeability with higher flux at gradient pH condition of pH 6.5 at apical and 7.4 at basolateral. Taken as whole, the major permeability related hurdles that hampered oral bioavailability of KBA included its gastrointestinal instability, CYP3A4 mediated intestinal metabolism, accumulation within the enterocytes and saturable kinetics. The present investigation may help in designing novel drug delivery system for KBA.

journal_name

Int J Pharm

authors

Bagul P,Khomane KS,Bansal AK

doi

10.1016/j.ijpharm.2014.01.019

subject

Has Abstract

pub_date

2014-04-10 00:00:00

pages

104-10

issue

1-2

eissn

0378-5173

issn

1873-3476

pii

S0378-5173(14)00029-5

journal_volume

464

pub_type

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