The influence of lipid digestion on the fate of orally administered drug delivery vehicles

Abstract

This review will focus on orally administered lipid-based drug delivery vehicles and specifically the influence of lipid digestion on the structure of the carrier lipids and their entrained drug cargoes. Digestion of the formulation lipids, which are typically apolar triglycerides, generates amphiphilic monoglycerides and fatty acids that can self-assemble into a diverse array of liquid crystalline structures. Tracking the dynamic changes in self-assembly of the lipid digestion products during digestion has recently been made possible using synchrotron-based small angle X-ray scattering. The influence of lipid chain length and degree of unsaturation on the resulting lipid structuring will be described in the context of the critical packing parameter theory. The chemical and structural transformation of the formulation lipids can also have a dramatic impact on the physical state of drugs co-administered with the formulation. It is often assumed that the best strategy for drug development is to maximise drug solubility in the undigested formulation lipids and to incorporate additives to maintain drug solubility during digestion. However, it is possible to improve drug absorption using lipid digestion in cases where the solubility of the dosed drug or one of its polymorphic forms is greater in the digested lipids. Three different fates for drugs administered with digestible lipid-based formulations will be discussed: (1) where the drug is more soluble in the undigested formulation lipids; (2) where the drug undergoes a polymorphic transformation during lipid digestion; and (3) where the drug is more soluble in the digested formulation lipids.

Revisiting the Dissolution of Praziquantel in Biorelevant Media and the Impact of Digestion of Milk on Drug Dissolution

“…A decrease in the intensity of Bragg peaks characteristic of the crystalline drug during digestion (not dispersion) indicates solubilisation is occurring as a consequence of digestion. The scattering is able to be acquired with a time resolution on the order of seconds to minutes, i.e., physiologically relevant time scale, by using a synchrotron X-ray source [ 9 , 10 , 19 , 24 ]. It is worth noting that these digestion experiments were not performed in a USP dissolution vessel, but scaled down to a smaller volume in vitro digestion apparatus.…”

Interplay of Hydropathy and Heterogeneous Diffusion in the Molecular Transport within Lamellar Lipid Mesophases

“…In particular, heterogeneity, reproducibility, and high biocompatibility of lipid mesophases have made them a potential tool for drug and nutraceutical delivery [ 14 ]. Moreover, the rich structural landscape of lipid mesophases has recently been shown to be naturally explored during digestion of tryglycerides, which likely impacts the delivery of drugs embedded in such hosts [ 16 ]. As a consequence, a large amount of research has been devoted to understanding how the chemical and structural features of lipid mesophases influence their transport properties [ 5 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ].…”

Small-volume in vitro lipid digestion measurements for assessing drug dissolution in lipid-based formulations using SAXS

“…SAXS can be used to characterise changes in the mesophases of lipid-based drug delivery systems under stimuli including changes in pH ( Li et al, 2019 ; Mertins et al, 2020 ; Fong et al, 2020 ), changes in temperature ( Tran et al, 2018 ; Fong et al, 2009 , Fong et al, 2014 ), exposure to endogenous surfactants and cells ( Fornasier et al, 2021 ; Bor et al, 2022 ), and digestion ( Clulow et al, 2018 , Salentinig et al, 2013 , Salentinig et al, 2015 ; Salim et al, 2019c ; Warren et al, 2011 ; Khan et al, 2016b ; Salvati Manni et al, 2021 ; Thorn et al, 2020 ). The use of a high-flux synchrotron X-ray source enables a time-resolved method to study these dynamic transitions between liquid crystalline structures during digestion ( Boyd and Clulow, 2021 ). Concurrently, the presence of crystalline drug can also be directly monitored through X-ray diffraction at wider angles.…”