Study of drug concentration effects on in vitro lipolysis kinetics in medium-chain triglycerides by considering oil viscosity and surface tension

Interactions of Artefenomel (OZ439) with Milk during Digestion: Insights into Digestion-Driven Solubilization and Polymorphic Transformations

“…Changes in the structures were therefore not attributable to the different extents of digestion. The influence of loading of amphiphilic drug on the release of fatty acids from LBFs has been reported previously with variable findings. − For example, Williams et al reported no significant effects of varying the concentration of danazol on the digestibility of medium and long chain lipids, while Thomas et al. observed a decrease in the titrated fatty acids as a function of simvastatin concentration during digestion in medium chain-SNEDDS but not long chain-SNEDDS .…”

“…suggested that the presence of a variety of amphiphilic drugs (including danazol) in LBFs reduced the extent of lipolysis of medium chain triglycerides . While the basis of the discrepancies between these observations were not initially clear due to the complexity of the mechanisms involved, it was generally recognized that poorly water-soluble drugs may change the surface compositions of the lipid droplets available for digestion. , This could arise from interactions between the drugs and the lipid droplets, surface localization, or partial solubilization of the drugs. , In addition to the effects of drugs on the removal of lipolytic products from the oil/water interface through changes in surface characteristics, interactions between the drugs and the lipid digestion products such as ion-pairing may also occur, which could potentially affect the formation of liquid crystalline structures as was seen in the case of OZ439 in milk.…”

“…37 Contrary to Williams et al, 38 studies by Arnold et al suggested that the presence of a variety of amphiphilic drugs (including danazol) in LBFs reduced the extent of lipolysis of medium chain triglycerides. 36 While the basis of the discrepancies between these observations were not initially clear due to the complexity of the mechanisms involved, it was generally recognized that poorly water-soluble drugs may change the surface compositions of the lipid droplets available for digestion. 36,37 This could arise from interactions between the drugs and the lipid droplets, surface localization, or partial solubilization of the drugs.…”

“…36,37 This could arise from interactions between the drugs and the lipid droplets, surface localization, or partial solubilization of the drugs. 36,37 In addition to the effects of drugs on the removal of lipolytic products from the oil/water interface through changes in surface characteristics, interactions between the drugs and the lipid digestion products such as ion-pairing may also occur, which could potentially affect the formation of liquid crystalline structures as was seen in the case of OZ439 in milk. Solid-State Properties of OZ439 Prior to Exposure to Milk.…”

Insights into Drug Precipitation Kinetics during In Vitro Digestion of a Lipid-Based Drug Delivery System Using In-Line Raman Spectroscopy and Mathematical Modeling

“…The improvement of oral bioavailability is largely governed by the fate of the LBDDS in the gut. In addition to formulation dispersion, digestion represents a particularly critical step, because hydrolyzed glycerides and some surfactants exhibit a change in polarity (5)(6)(7). Thus, the capacity of a formulation to solubilize a drug may be progressively reduced, developing an increased risk of drug precipitation.…”