Separation and Characterization of the Colloidal Phases Produced on Digestion of Common Formulation Lipids and Assessment of Their Impact on the Apparent Solubility of Selected Poorly Water-Soluble Drugs

Use of in vitro lipid digestion data to explain the in vivo performance of triglyceride-based oral lipid formulations of poorly water-soluble drugs: Studies with halofantrine

“…18 The medium chain digests also appeared to support supersaturation, at least for the most lipophilic drugs (Hf and cinnarizine). 1 The high concentrations of lipid produced in the aqueous phase of the MCT in vitro digests therefore appears to result in the production of both micellar and vesicular structures, 18 which are capable of supporting supersaturated concentrations of Hf. In contrast, however, during in vivo processing, the continuous removal of lipid digestion products by absorption and the potential for an increase in the concentration of bile salt micelles in the intestine in response to the presence of luminal lipid, may have resulted in solubilization of the vesicular species into a purely micellar phase leading to failure to attain the same high aqueous concentrations observed in vitro.…”

“…Previous studies have shown that at lipid concentrations similar to those expected to be obtained during the course of an in vitro digestion experiment (250 mg MCT or LCT in a 10 mL digest volume), both mixed micellar and vesicular species are formed. 18 In addition, at bile salt concentrations representative of fasted intestinal conditions (5 mM BS), 19,20 the importance of the vesicular phase to the overall solubilization capacity of the digest was previously found to be significantly higher for the medium chain digests (where the vesicles accounted for >85% of the solubilization capacity for Hf), when compared with the long chain digests (<25% of the total solubilization capacity for Hf). 18 The medium chain digests also appeared to support supersaturation, at least for the most lipophilic drugs (Hf and cinnarizine).…”

“…18 In addition, at bile salt concentrations representative of fasted intestinal conditions (5 mM BS), 19,20 the importance of the vesicular phase to the overall solubilization capacity of the digest was previously found to be significantly higher for the medium chain digests (where the vesicles accounted for >85% of the solubilization capacity for Hf), when compared with the long chain digests (<25% of the total solubilization capacity for Hf). 18 The medium chain digests also appeared to support supersaturation, at least for the most lipophilic drugs (Hf and cinnarizine). 1 The high concentrations of lipid produced in the aqueous phase of the MCT in vitro digests therefore appears to result in the production of both micellar and vesicular structures, 18 which are capable of supporting supersaturated concentrations of Hf.…”

Liquid Proliposomes of Nimodipine Drug Delivery System: Preparation, Characterization, and Pharmacokinetics

“…Figure 1c, d showed that the disintegration of soft capsule shells had not affected the formation of liposomes, and the same intact spherical morphology of liposomes was observed. In addition, sodium deoxycholate incorporated into the formulation could facilitate liposome formation, for that it was reported that lipids containing bile salts can readily transform into vesicular or mixed micelles in the gastrointestinal environment (20)(21)(22)(23)(24). It could be assumed that proliposomes would convert into liposomes upon contact with physiological fluids present in the body after oral administration.…”

Physicochemical Characterization of Simulated Intestinal Fed-State Fluids Containing Lyso-Phosphatidylcholine and Cholesterol

“…The intermediate phases produced during lipid digestion can play a significant role in drug solubilization and trafficking in the gastrointestinal tract, thereby influencing the overall performance of the formulation (9,10). In light of this, characterization of such media can offer important information on the role of intermediate phases of lipid digestion and drug solubilization in the gastrointestinal tract.…”