Drug supersaturation during formulation digestion, including real-time analytical approaches

Kuentz, Martin

doi:10.1016/j.addr.2018.11.003

Cited by 38 publications

(17 citation statements)

References 101 publications

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“…To develop su-SEDDSs, it is essential to understand the basic concepts of solubility, supersaturation, and absorption. The advantages of absorption by supersaturation can be explained by the following theories [34,43,44]. Drug absorption can be assessed by Fick's First law; thus, the drug absorption via passive drug diffusion is driven by the maximum concentration in GIT: J = dM/dt = S·P·C (10) The nucleation rate (J n ) is estimated by:…”

Section: Increase In Absorption By Supersaturation In the Gitmentioning

confidence: 99%

“…The importance of supersaturation maintenance in vivo has already been addressed in many earlier studies in the literature [18,34,[52][53][54]. The theoretical concept behind the generation and maintenance of a supersaturated state is commonly described by the "spring and parachute" theory [5,18,34,43,52,[55][56][57]. This theory is explained in a slightly modified manner for su-SEDDS as shown in Figure 3 below, considering the induction of supersaturation caused by some different factors (e.g., dispersion and digestion in GIT) in lipid-based formulations [58].…”

Section: Maintenance Of a Supersaturated State For The Improvement Ofmentioning

confidence: 99%

“…In the field of oral drug delivery, in vitro models are commonly used in the pharmaceutical development phase to estimate in vivo drug performance and optimize formulation design prior to preclinical and clinical studies [5,7,13,18,42,43,56]. To improve the accuracy of in vivo dissolution predictions using in vitro dissolution, defined dissolution media that more accurately reflect the solubilization processes in vivo need to be developed [25,52,61].…”

Section: Biorelevant Supersaturation Testingmentioning

confidence: 99%

“…There has been a development of a range of in vitro models simulating the digestion processes occurring in the GIT to evaluate SEDDSs. Many reviews have been reported, including detailed explanations [25,43]. This section will explain very briefly the most commonly used in vitro digestion models, i.e., the pH-stat lipolysis model, the dynamic gastric model (DGM), and the high-throughput (HTP) lipolysis model, and latest research trends including real-time analysis and digestion-permeation models, in which physiological effects taken into account.…”

Section: In Vitro Digestion Modelmentioning

confidence: 99%

“…Real-time analysis, combined with the abovementioned approaches, could be an excellent alternative method with a high level of sophistication to truly capture the dynamics of su-SEDDSs [43]. Specifically, evaluation using real-time techniques can measure in vitro kinetic changes.…”

Section: Real-time Analysismentioning

confidence: 99%

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Current Status of Supersaturable Self-Emulsifying Drug Delivery Systems

Park

Kim

2020

Pharmaceutics

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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.Pharmaceutics 2020, 12, 365 2 of 57 intraluminal supersaturation and the biorelevance of supersaturation assays will be addressed. Finally, we will make suggestions for the successful development of su-SEDDs.There are many review articles that give useful information about the nature and application of supersaturable drug delivery systems or conventional SEDDSs. However, these reviews cover only a limited range of su-SEDDSs. Therefore, 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. Conventional Solubilized SEDDSsThere has been a steady increase in the number of new drug candidates (almost 40%) that are highly hydrophobic and poorly water-soluble. The oral bioavailability of poorly water-soluble drugs is hindered by low solubility and slow dissolution in the aqueous environment of the GIT. Thus, it is a great challenge for pharmaceutical scientists to overcome the inherent slow dissolution and poor oral absorption of hydrophobic drugs [1][2][3][4]. SEDDSs have emerged as a promising approach to improving the biopharmaceutical performance of hydrophobic drugs by enhancing their bioavailability [5,6].An SEDDS is a pre-concentrate composed of a drug, oils, surfactants, and sometimes co-solvents and/or co-surfactan...

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Section: Increase In Absorption By Supersaturation In the Gitmentioning

confidence: 99%