Lipid-associated oral delivery: Mechanisms and analysis of oral absorption enhancement

Abstract

The majority of newly discovered oral drugs are poorly water soluble, and co-administration with lipids has proven effective in significantly enhancing bioavailability of some compounds with low aqueous solubility. Yet, lipid-based delivery technologies have not been widely employed in commercial oral products. Lipids can impact drug transport and fate in the gastrointestinal (GI) tract through multiple mechanisms including enhancement of solubility and dissolution kinetics, enhancement of permeation through the intestinal mucosa, and triggering drug precipitation upon lipid emulsion depletion (e.g., by digestion). The effect of lipids on drug absorption is currently not quantitatively predictable, in part due to the multiple complex dynamic processes that can be impacted by lipids. Quantitative mechanistic analysis of the processes significant to lipid system function and overall impact on drug absorption can aid understanding of drug-lipid interactions in the GI tract and exploitation of such interactions to achieve optimal lipid-based drug delivery. In this review, we discuss the impact of co-delivered lipids and lipid digestion on drug dissolution, partitioning, and absorption in the context of the experimental tools and associated kinetic expressions used to study and model these processes. The potential benefit of a systems-based consideration of the concurrent multiple dynamic processes occurring upon co-dosing lipids and drugs to predict the impact of lipids on drug absorption and enable rational design of lipid-based delivery systems is presented.

Enhanced oral absorption of pemetrexed by ion-pairing complex formation with deoxycholic acid derivative and multiple nanoemulsion formulations: preparation, characterization, and in vivo oral bioavailability and anticancer effect

“…However, oral absorption of a lipid-based formulation can be readily affected by dietary intake, lipid digestion, lipid emulsifiers such as bile salts, and dilution effect in and the pH of GI fluids. 27 In addition, many organic solvents were used to prepare the lipid/drug conjugate. However, when a drug is conjugated with a cell recognition moiety such as a International Journal of Nanomedicine 2018:13 submit your manuscript | www.dovepress.com…”

Enzymatically Modified Shea Butter and Palm Kernel Oil as Potential Lipid Drug Delivery Matrices

“…[1,2] Consequently, many of these compounds come along with limited and often highly variable bioavailability (BA) and place a significant burden on drug development. [3] However, for many of these APIs, particularly for BCS class II compounds, there is a good chance of enhancing bioavailability and also decreasing its variability by utilizing drug delivery strategies ensuring that the API is readily and completely dissolved in the lumen of the upper gastrointestinal (GI) tract.…”

Comparison of mechanistic model predicting the role of ingested lipids in oral dissolution of griseofulvin

“…SBO and FO) are used in formulation of lipid-based drug delivery systems [19,[31][32][33][34][35], and lipids can also impact drug absorption when drug is coadministered with food-associated lipid. The mechanism and analysis of drug delivery involving lipids have been reported by our lab and others illustrating that lipid-based formulations have great potential for facilitating effective hydrophobic oral drug delivery [36,37].…”

“…The composition of simulated fluids containing model bile micelles at fed concentration is summarized in Table 2 [36]. The fed state solution was prepared for all lipid digestion and drug dissolution studies reported in this thesis as 4X concentration to allow room for dilution to a 1X concentration model lipid and lipase.…”