Abstract:
The interactions of irbesartan (IRB) and irbesartan–2-hydroxypropyl-β-cyclodextrin (HP-β-CD) complex with dipalmitoyl phosphatidylcholine (DPPC) bilayers have been explored utilizing an array of biophysical techniques ranging from differential scanning calorimetry (DSC), small angle X-ray scattering (SAXS), ESI mass spectrometry (ESI-MS) and solid state nuclear magnetic resonance (ssNMR). Molecular dynamics (MD) calculations have been also conducted to complement the experimental results. Irbesartan was found to be embedded in the lipid membrane core and to affect the phase transition properties of the DPPC bilayers. SAXS studies revealed that irbesartan alone does not display perfect solvation since some coexisting irbesartan crystallites are present. In its complexed form IRB gets fully solvated in the membranes showing that encapsulation of IRB in HP-β-CD may have beneficial effects in the ADME properties of this drug. MD experiments revealed the topological and orientational integration of irbesartan into the phospholipid bilayer being placed at about 1 nm from the membrane centre. © 2017 Elsevier B.V.
Authors:
Liossi, A.S.
Ntountaniotis, D.
Kellici, T.F.
Chatziathanasiadou, M.V.
Megariotis, G.
Mania, M.
Becker-Baldus, J.
Kriechbaum, M.
Krajnc, A.
Christodoulou, E.
Glaubitz, C.
Rappolt, M.
Amenitsch, H.
Mali, G.
Theodorou, D.N.
Valsami, G.
Pitsikalis, M.
Iatrou, H.
Tzakos, A.G.
Mavromoustakos, T.
Keywords:
dipalmitoylphosphatidylcholine; irbesartan; irbesartan 2 hydroxypropyl beta cyclodextrin complex; irbesartan derivative; unclassified drug; 2-hydroxypropyl-beta-cyclodextrin; antihypertensive agent; beta cyclodextrin derivative; biphenyl derivative; dipalmitoylphosphatidylcholine; irbesartan; lipid bilayer; liposome; tetrazole derivative, Article; biophysics; controlled study; crystal structure; differential scanning calorimetry; drug dosage form comparison; drug interaction; encapsulation; lipid bilayer; mass spectrometry; molecular dynamics; nuclear magnetic resonance; phase transition; solvation; X ray crystallography; chemistry; drug formulation; freeze drying; kinetics; lipid bilayer; thermodynamics, 1,2-Dipalmitoylphosphatidylcholine; Antihypertensive Agents; beta-Cyclodextrins; Biphenyl Compounds; Drug Compounding; Freeze Drying; Kinetics; Lipid Bilayers; Liposomes; Molecular Dynamics Simulation; Phase Transition; Tetrazoles; Thermodynamics
