Intrinsic lipolysis rate for systematic design of lipid-based formulations

Abstract

Lipid-based formulations (LBFs) are used by the pharmaceutical industry in oral delivery systems for both poorly water-soluble drugs and biologics. Digestibility is key for the performance of LBFs and in vitro lipolysis is commonly used to compare the digestibility of LBFs. Results from in vitro lipolysis experiments depend highly on the experimental conditions and formulation characteristics, such as droplet size (which defines the surface area available for digestion) and interfacial structure. This study introduced the intrinsic lipolysis rate (ILR) as a surface area-independent approach to compare lipid digestibility. Pure acylglycerol nanoemulsions, stabilized with polysorbate 80 at low concentration, were formulated and digested according to a standardized pH–stat lipolysis protocol. A methodology originally developed to calculate the intrinsic dissolution rate of poorly water-soluble drugs was adapted for the rapid calculation of ILR from lipolysis data. The impact of surfactant concentration on the apparent lipolysis rate and lipid structure on ILR was systematically investigated. The surfactant polysorbate 80 inhibited lipolysis of tricaprylin nanoemulsions in a concentration-dependent manner. Coarse-grained molecular dynamics simulations supported these experimental observations. In the absence of bile and phospholipids, tricaprylin was shielded from lipase at 0.25% polysorbate 80. In contrast, the inclusion of bile salt and phospholipid increased the surfactant-free area and improved the colloidal presentation of the lipids to the enzyme, especially at 0.125% polysorbate 80. At a constant and low surfactant content, acylglycerol digestibility increased with decreasing acyl chain length, decreased esterification, and increasing unsaturation. The calculated ILR of pure acylglycerols was successfully used to accurately predict the IRL of binary lipid mixtures. The ILR measurements hold great promise as an efficient method supporting pharmaceutical formulation scientists in the design of LBFs with specific digestion profiles. Graphical abstract

The consumption of iceberg lettuce may reduce the adhesion of dietary fat to the mucus surface of the stomach barrier lining decreasing the risk of triggering acute gastroesophageal reflux

“…Surfactants occur in saliva with a surface tension of 53-65mN/m, gastric fluid (43-54mN/m), the small intestine as bile salts (25-28mN/m which may also be present in gastric fluid) and in DWD (22-35 mN/m) [19][20][21][22][23]. An in vitro study to show how SF influence the digestibility of the fat tricaprylin, in the presence of the SF polysorbate 80 found that at low SF concentrations and in the presence of other types of SF (bile salts and phospholipids), adsorbed SF molecules can be displaced and allow lipolysis to occur in a concentration dependent manner [24]. Research involving the use of SF to prevent GERD was not found to be reported, possibly because lingual and gastric surfactants are not available for purchase and were not found included in standard (INFOGEST) in vitro gastric digestion methods [25].…”