TY - JOUR

T1 - Fed and fasted state gastro-intestinal in vitro lipolysis

T2 - In vitro in vivo relations of a conventional tablet, a SNEDDS and a solidified SNEDDS

AU - Christophersen, Philip Carsten B

AU - Christiansen, Martin Lau

AU - Holm, Rene

AU - Kristensen, Jakob

AU - Jacobsen, Jette

AU - Abrahamsson, Bertil

AU - Müllertz, Anette

N1 - Copyright © 2013. Published by Elsevier B.V.

PY - 2014

Y1 - 2014

N2 - The present study aims at evaluating the ability of a gastro-intestinal in vitro lipolysis model to predict the performance of two lipid formulations and a conventional tablet containing a poorly soluble drug, cinnarizine, in dogs, both in the fasted and fed state. A self-nano-emulsifying drug delivery system (SNEDDS) was either dosed in a hard gelatin capsule (SNEDDS-C) or loaded onto a porous tablet core (SNEDDS-T) and compared to a marketed conventional tablet (Conv) in an in vitro lipolysis model. The model simulates the digestion in the stomach and intestine during either the fasted or the fed state. Whole fat milk (3.5 %) was used in the fed state model to mimic the dynamic lipolysis events after ingestion of food. The results were compared to a dog study in this issue. In the fasted state in vitro lipolysis model, the amount of solubilized cinnarizine decreased in the order SNEDDS-C>SNEDDS-T>Conv, which correlated well with the in vivo bioavailability. In the fed state in vitro lipolysis model, cinnarizine was solubilized to the same degree for all formulations. Compared to the fasted state model, only the performance of the conventional tablet was improved, indicating food effect. This correlated with the in vivo study, where the tablet was the only formulation with a significant food effect. The fasted state model correlated well with the in vivo results and although the fed state model did not accurately predict the fed state in vivo results, it could predict which formulation that would exhibit a food effect.

AB - The present study aims at evaluating the ability of a gastro-intestinal in vitro lipolysis model to predict the performance of two lipid formulations and a conventional tablet containing a poorly soluble drug, cinnarizine, in dogs, both in the fasted and fed state. A self-nano-emulsifying drug delivery system (SNEDDS) was either dosed in a hard gelatin capsule (SNEDDS-C) or loaded onto a porous tablet core (SNEDDS-T) and compared to a marketed conventional tablet (Conv) in an in vitro lipolysis model. The model simulates the digestion in the stomach and intestine during either the fasted or the fed state. Whole fat milk (3.5 %) was used in the fed state model to mimic the dynamic lipolysis events after ingestion of food. The results were compared to a dog study in this issue. In the fasted state in vitro lipolysis model, the amount of solubilized cinnarizine decreased in the order SNEDDS-C>SNEDDS-T>Conv, which correlated well with the in vivo bioavailability. In the fed state in vitro lipolysis model, cinnarizine was solubilized to the same degree for all formulations. Compared to the fasted state model, only the performance of the conventional tablet was improved, indicating food effect. This correlated with the in vivo study, where the tablet was the only formulation with a significant food effect. The fasted state model correlated well with the in vivo results and although the fed state model did not accurately predict the fed state in vivo results, it could predict which formulation that would exhibit a food effect.

U2 - 10.1016/j.ejps.2013.09.007

DO - 10.1016/j.ejps.2013.09.007

M3 - Journal article

C2 - 24056027

VL - 57

SP - 232

EP - 239

JO - Norvegica Pharmaceutica Acta

JF - Norvegica Pharmaceutica Acta

SN - 0928-0987

ER -