Evaluation of the in-vitro digestion profiles of long and medium chain glycerides and the phase behaviour of their lipolytic products

Abstract

An evaluation of the in-vitro digestion profile and phase behaviour of the common formulation lipids Miglyol 812 (medium chain triglyceride, MCT), Capmul MCM (C8/C10 monoglyceride/ diglyceride mixture), soybean oil (long chain triglyceride, LCT) and Maisine 35-1 (C18 monoglyceride/diglyceride mixture), is described. Experiments were conducted using titrimetric, high-performance thin-layer chromatographic (HPTLC) and ultracentrifugational techniques under model fasted and post-prandial intestinal conditions. The rate and extent of digestion of the medium chain lipids was greater than the corresponding long chain lipids, and independent of bile salt concentration, with complete conversion to monoglyceride and fatty acid occurring after 30 min digestion. The long chain lipid digests separated into an oily phase (containing undigested triglyceride and diglyceride), an aqueous phase (containing bile salt, fatty acid and monoglyceride) and a pellet phase (containing approximately 5 mm of fatty acid, presumably as an insoluble soap) after ultracentrifugation. Higher proportions of long chain fatty acid and monoglyceride were dispersed into the aqueous phase with increasing bile salt concentrations. In contrast, medium chain lipolytic products separated only into an aqueous phase and a pellet fraction in a bile-salt-independent manner. The digestion of both the C8/C10 and C18 monoglyceride/diglyceride lipid mixtures was more rapid than the corresponding triglyceride, especially at early time points. This investigation provides insight into the relative digestion kinetics of medium chain and long chain lipids and provides information regarding the phase behaviour of their lipolytic products under conditions modelled on those expected after oral administration. The data also provide a background for improved understanding of the potential utility of long chain and medium chain lipid-based formulations.

Effect of Lipolysis on Drug Release from Self-microemulsifying Drug Delivery Systems (SMEDDS) with Different Core/Shell Drug Location

“…The results are in good agreement with previous reports where the rate and extent of digestion of medium-chain lipids were greater than for the long-chain lipids (23,41,42). Among the lipolytic products of three oil phases (caprylic/capric acids, oleic acids, and ricinoleic acids), the medium-chain caprylic/capric acids were more apt to be ionized than long-chain oleic acids and ricinoleic acids at physiological pH (23,40). Therefore, the medium-chain acids were more soluble in the aqueous phase and more prone to form calcium soaps, which means that the clearance rates of mediumchain lipid products from the o/w interface were more rapid.…”

“…MCT was completely hydrolyzed during 1 h of digestion, while the percentages of digested ethyl oleate and castor oil were just 13.8% and 23.5%, respectively. The results are in good agreement with previous reports where the rate and extent of digestion of medium-chain lipids were greater than for the long-chain lipids (23,41,42). Among the lipolytic products of three oil phases (caprylic/capric acids, oleic acids, and ricinoleic acids), the medium-chain caprylic/capric acids were more apt to be ionized than long-chain oleic acids and ricinoleic acids at physiological pH (23,40).…”

“…In vitro lipolysis experiments were conducted using an in vitro lipid digestion model with a pH-Stat automatic titration unit (848 Titrino plus, Metrohm AG, Herisau, Switzerland) (22,23). The lipolysis of SMEDDS and oil solution (MCT, ethyl oleate, and castor oil) were determined in separate experiments.…”

Design of Lipid-Based Formulations for Oral Administration of Poorly Water-Soluble Drug Fenofibrate: Effects of Digestion

“…Fed and fasted intestinal contents were simulated utilising 20 and 5 mM bile salt, respectively. Phospholipids were included in the digestion mixture at a bile salt/phospholipid molar ratio of 4:1, which is the ratio secreted in bile (22). The lipid formulations were emulsified in the mixed micellar solutions prior to enzyme addition by stirring continuously for 10 min in the thermostatic jacketed glass reaction vessel.…”

An Improved Formulation Screening and Optimization Method Applied to the Development of a Self-Microemulsifying Drug Delivery System

“…8) In vitro lipolysis may therefore be an appropriate indicator of performance, and models of in vitro lipid digestion have recently been developed to assist in the design of lipid-based formulations. 7,9,10) Based on these findings, solubilization capacity under a digestion condition was established as a valuable response instead of in situ intestinal absorption in this study.…”