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.
Highlights
Changes in lipid composition during digestion and associated lipid self-assemblyNature has developed enzymes as a means of controlling complex structural changes in biomaterials in our body
While the phenomenon is well studied in static biorelevant media during dissolution studies [62] there are few reports of such behaviour during in situ digestion and almost none have been measured using synchrotron X-ray scattering during lipid digestion
To enable the rational design of optimal lipid-based drug delivery systems the physical-chemical complexity in these systems should be harnessed, which in turn requires a clear understanding of the structural properties of lipids during these transformations
Summary
Changes in lipid composition during digestion and associated lipid self-assemblyNature has developed enzymes as a means of controlling complex structural changes in biomaterials in our body. The periodic fluctuations in electron density found in a repetitive crystalline structure such as those in the self-assembled lipid phases or the powders of crystalline drugs leads to diffraction, specific angles at which X-rays are scattered strongly through constructive interference of the outgoing waves after interaction with the sample. The following sections will discuss time-resolved X-ray scattering studies on the digestion of lipid-based drug delivery systems and the observed impacts on lipid and drug structuring.
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