Abstract
Self-emulsifying drug delivery systems (SEDDSs) are a vital strategy to enhance the bioavailability (BA) of formulations of poorly water-soluble compounds. However, these formulations have certain limitations, including in vivo drug precipitation, poor in vitro in vivo correlation due to a lack of predictive in vitro tests, issues in handling of liquid formulation, and physico-chemical instability of drug and/or vehicle components. To overcome these limitations, which restrict the potential usage of such systems, the supersaturable SEDDSs (su-SEDDSs) have gained attention based on the fact that the inclusion of precipitation inhibitors (PIs) within SEDDSs helps maintain drug supersaturation after dispersion and digestion in the gastrointestinal tract. This improves the BA of drugs and reduces the variability of exposure. In addition, the formulation of solid su-SEDDSs has helped to overcome disadvantages of liquid or capsule dosage form. This review article discusses, in detail, the current status of su-SEDDSs that overcome the limitations of conventional SEDDSs. It discusses the definition and range of su-SEDDSs, the principle mechanisms underlying precipitation inhibition and enhanced in vivo absorption, drug application cases, biorelevance in vitro digestion models, and the development of liquid su-SEDDSs to solid dosage forms. This review also describes the effects of various physiological factors and the potential interactions between PIs and lipid, lipase or lipid digested products on the in vivo performance of su-SEDDSs. In particular, several considerations relating to the properties of PIs are discussed from various perspectives.
Highlights
Su-self-emulsifying drug delivery systems (SEDDSs) technology as an absorption-enhancing strategy has advanced and several approaches to reducing drug precipitation from supersaturated state of SEDDS in gastrointestinal tract (GIT) have been attempted; several questions have been raised regarding supersaturation in the GIT. These include: are su-SEDDSs truly effective in significantly enhancing in vivo drug absorption? If so, what processes are involved? How does GI physiology, such as the composition of GI fluid and hydrodynamics, affect intraluminal supersaturation, and how is this influenced by various internal and external factors, such as food, age, and disease? What is more important in the significant enhancement of in vivo drug absorption, the degree of supersaturation or the stability of supersaturation? How can we improve the biorelevance of in vitro digestion and supersaturation testing to achieve better in vitro–in vivo correlations (IVIVCs)? Many research approaches have attempted to meet these intellectual needs, and this review focuses on and discusses these major issues
-precipitation inhibitors (PIs) effect: Soluplus > hydroxypropyl methylcellulose (HPMC), PVP. -Concentration dependent PI effect -In vivo in SD rats at a dose of 5 mg/kg, Similar or higher area under the curve (AUC) and Cmax of su-SEDDS containing one-quarter the amount of vehicle compared to conventional SEDDS
Su-SEDDSs are a promising approach for the formulation of poorly water-soluble drugs to enhance their bioavailability through the induction and stabilization by PIs of a supersaturated drug state in the GI fluid
Summary
Supersaturable formulations induce a supersaturated drug concentration and maintain drugs in a supersaturated state when exposed to the aqueous environment of the gastrointestinal tract (GIT) This synergic effect can be achieved through co-formulation with precipitation inhibitors (PIs). Inducing supersaturation in the GIT is an increasingly popular means of promoting the oral absorption of poorly water-soluble drugs. This concept has been applied to self-emulsifying drug delivery systems (SEDDSs), resulting in great advancement. This review focuses on the current status of supersaturable SEDDSs (su-SEDDSs) as a promising strategy to induce supersaturation and maintain it in the GIT, thereby enhancing the intestinal absorption of poorly water-soluble drugs. This review, which includes the current status of technology focused only on su-SEDDSs, is a valuable addition to the previous review literature because no review article currently covers such a wide range of su-SEDDSs
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