title: Effect of phospholipid-based formulations of Boswellia serrata extract on the solubility, permeability, and absorption of the individual boswellic acid constituents present.
abstract: Boswellia serrata gum resin extracts are used widely for the treatment of inflammatory diseases. However, very low concentrations in the plasma and brain were observed for the boswellic acids (1-6, the active constituents of B. serrata). The present study investigated the effect of phospholipids alone and in combination with common co-surfactants (e.g., Tween 80, vitamin E-TPGS, pluronic f127) on the solubility of 1-6 in physiologically relevant media and on the permeability in the Caco-2 cell model. Because of the high lipophilicity of 1-6, the permeability experiments were adapted to physiological conditions using modified fasted state simulated intestinal fluid as apical (donor) medium and 4% bovine serum albumin in the basolateral (receiver) compartment. A formulation composed of extract/phospholipid/pluronic f127 (1:1:1 w/w/w) increased the solubility of 1-6 up to 54 times compared with the nonformulated extract and exhibited the highest mass net flux in the permeability tests. The oral administration of this formulation to rats (240 mg/kg) resulted in 26 and 14 times higher plasma levels for 11-keto-β-boswellic acid (1) and acetyl-11-keto-β-boswellic acid (2), respectively. In the brain, five times higher levels for 2 compared to the nonformulated extract were determined 8 h after oral administration.
authors.affiliation: Central Laboratory of German Pharmacists , Carl-Mannich-Straße 20, 65760 Eschborn, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Hüsch
authors.forename: Kathleen
authors.initials: K
authors.lastname: Gerbeth
authors.forename: Gert
authors.initials: G
authors.lastname: Fricker
authors.forename: Constanze
authors.initials: C
authors.lastname: Setzer
authors.forename: Jürgen
authors.initials: J
authors.lastname: Zirkel
authors.forename: Herbert
authors.initials: H
authors.lastname: Rebmann
authors.forename: Manfred
authors.initials: M
authors.lastname: Schubert-Zsilavecz
authors.forename: Mona
authors.initials: M
authors.lastname: Abdel-Tawab
mesh_terms: D000042:Absorption / Q000187:drug effects; D000284:Administration, Oral; D000818:Animals; D029743:Boswellia / Q000737:chemistry*; D001921:Brain / Q000187:drug effects; D018938:Caco-2 Cells; D006801:Humans; D008297:Male; D008954:Models, Biological; D010539:Permeability / Q000187:drug effects; D010743:Phospholipids / Q000493:pharmacokinetics*; D020442:Poloxamer / Q000032:analysis / Q000493:pharmacokinetics; D011136:Polysorbates / Q000032:analysis / Q000493:pharmacokinetics; D051381:Rats; D012995:Solubility / Q000187:drug effects; D013997:Time Factors; D014315:Triterpenes / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D014810:Vitamin E / Q000032:analysis / Q000493:pharmacokinetics
chemical_list: C447943:11-keto-boswellic acid; D010743:Phospholipids; D011136:Polysorbates; D014315:Triterpenes; C094432:acetyl-11-ketoboswellic acid; D020442:Poloxamer; D014810:Vitamin E; C054625:boswellic acid