TY - JOUR
T1 - Solution or suspension - Does it matter for lipid based systems?
T2 - In vivo studies of chase dosing lipid vehicles with aqueous suspensions of a poorly soluble drug
AU - Larsen, A T
AU - Holm, R
AU - Müllertz, A
N1 - Copyright © 2017 Elsevier B.V. All rights reserved.
PY - 2017/8/1
Y1 - 2017/8/1
N2 - In this study, the potential of co-administering an aqueous suspension with a placebo lipid vehicle, i.e. chase dosing, was investigated in rats relative to the aqueous suspension alone or a solution of the drug in the lipid vehicle. The lipid investigated in the present study was Labrafil M2125CS and three evaluated poorly soluble model compounds, danazol, cinnarizine and halofantrine. For cinnarizine and danazol the oral bioavailability in rats after chase dosing or dosing the compound dissolved in Labrafil M21515CS was similar and significantly higher than for the aqueous suspension. For halofantrine the chase dosed group had a tendency towards a low bioavailability relative to the Labrafil M2125CS solution, but still a significant higher bioavailability relative to the aqueous suspension. This could be due to factors such as a slower dissolution rate in the intestinal phase of halofantrine or a lower solubility in the colloidal structures formed during digestion, but other mechanisms may also be involved. The study thereby supported the potential of chase dosing as a potential dosing regimen in situations where it is beneficial to have a drug in the solid state, e.g. due to chemical stability issues in the lipid vehicle.
AB - In this study, the potential of co-administering an aqueous suspension with a placebo lipid vehicle, i.e. chase dosing, was investigated in rats relative to the aqueous suspension alone or a solution of the drug in the lipid vehicle. The lipid investigated in the present study was Labrafil M2125CS and three evaluated poorly soluble model compounds, danazol, cinnarizine and halofantrine. For cinnarizine and danazol the oral bioavailability in rats after chase dosing or dosing the compound dissolved in Labrafil M21515CS was similar and significantly higher than for the aqueous suspension. For halofantrine the chase dosed group had a tendency towards a low bioavailability relative to the Labrafil M2125CS solution, but still a significant higher bioavailability relative to the aqueous suspension. This could be due to factors such as a slower dissolution rate in the intestinal phase of halofantrine or a lower solubility in the colloidal structures formed during digestion, but other mechanisms may also be involved. The study thereby supported the potential of chase dosing as a potential dosing regimen in situations where it is beneficial to have a drug in the solid state, e.g. due to chemical stability issues in the lipid vehicle.
KW - Journal Article
U2 - 10.1016/j.ejpb.2017.04.023
DO - 10.1016/j.ejpb.2017.04.023
M3 - Journal article
C2 - 28465239
SN - 0939-6411
VL - 117
SP - 308
EP - 314
JO - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
JF - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
ER -