Development of a high-throughput in vitro intestinal lipolysis model for rapid screening of lipid-based drug delivery systems
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Development of a high-throughput in vitro intestinal lipolysis model for rapid screening of lipid-based drug delivery systems. / Mosgaard, Mette D; Sassene, Philip; Mu, Huiling; Rades, Thomas; Müllertz, Anette.
In: European Journal of Pharmaceutics and Biopharmaceutics, Vol. 94, 08.2015, p. 493-500.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Development of a high-throughput in vitro intestinal lipolysis model for rapid screening of lipid-based drug delivery systems
AU - Mosgaard, Mette D
AU - Sassene, Philip
AU - Mu, Huiling
AU - Rades, Thomas
AU - Müllertz, Anette
N1 - Copyright © 2015. Published by Elsevier B.V.
PY - 2015/8
Y1 - 2015/8
N2 - PURPOSE: To develop a high-throughput in vitro intestinal lipolysis (HTP) model, without any means of pH-stat-titration, to enable a fast evaluation of lipid-based drug delivery systems (LbDDS).MATERIAL AND METHOD: The HTP model was compared to the traditionally used dynamic in vitro lipolysis (DIVL) model with regard to the extent of lipid digestion and drug distribution of two poorly soluble model drugs (cinnarizine and danazol), during digestion of three LbDDS (LbDDS I-III).RESULT: The HTP model was able to maintain pH around 6.5 during digestion, without the addition of NaOH to neutralize the free fatty acids (FFAs), due to an increased buffer capacity. Cinnarizine was primarily located in the aqueous phase during digestion of all three LbDDS and did not differ significantly between the two models. The distribution of danazol varied from formulation to formulation, but no significant difference between the models was observed. The triacylglycerides (TAG) in LbDDS III were digested to the same extent in both models, whereas the TAG present in LbDDS II was digested slightly less in the HTP model. No TAG was present in LbDDS I and digestion was therefore not analyzed.CONCLUSION: The HTP model is able to predict drug distribution during digestion of LbDDS containing poorly water soluble drugs in the same manner as the DIVL model. Thus the HTP model might prove applicable for high-throughput evaluation of LbDDS in e.g. 96 well plates or small scale dissolution equipment.
AB - PURPOSE: To develop a high-throughput in vitro intestinal lipolysis (HTP) model, without any means of pH-stat-titration, to enable a fast evaluation of lipid-based drug delivery systems (LbDDS).MATERIAL AND METHOD: The HTP model was compared to the traditionally used dynamic in vitro lipolysis (DIVL) model with regard to the extent of lipid digestion and drug distribution of two poorly soluble model drugs (cinnarizine and danazol), during digestion of three LbDDS (LbDDS I-III).RESULT: The HTP model was able to maintain pH around 6.5 during digestion, without the addition of NaOH to neutralize the free fatty acids (FFAs), due to an increased buffer capacity. Cinnarizine was primarily located in the aqueous phase during digestion of all three LbDDS and did not differ significantly between the two models. The distribution of danazol varied from formulation to formulation, but no significant difference between the models was observed. The triacylglycerides (TAG) in LbDDS III were digested to the same extent in both models, whereas the TAG present in LbDDS II was digested slightly less in the HTP model. No TAG was present in LbDDS I and digestion was therefore not analyzed.CONCLUSION: The HTP model is able to predict drug distribution during digestion of LbDDS containing poorly water soluble drugs in the same manner as the DIVL model. Thus the HTP model might prove applicable for high-throughput evaluation of LbDDS in e.g. 96 well plates or small scale dissolution equipment.
KW - Chromatography, High Pressure Liquid
KW - Cinnarizine
KW - Danazol
KW - Drug Carriers
KW - High-Throughput Screening Assays
KW - Intestines
KW - Kinetics
KW - Lipids
KW - Lipolysis
KW - Models, Biological
KW - Particle Size
U2 - 10.1016/j.ejpb.2015.06.028
DO - 10.1016/j.ejpb.2015.06.028
M3 - Journal article
C2 - 26159837
VL - 94
SP - 493
EP - 500
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
SN - 0939-6411
ER -
ID: 161623704