Successful development of oral SEDDS: screening of excipients from the industrial point of view

Nardin, Isabelle; Köllner, S.

doi:10.1016/j.addr.2018.10.014

Cited by 65 publications

(28 citation statements)

References 54 publications

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“…Our previous work has shown that AVO and its individual constituents have limited aqueous solubility. Thus, we evaluated if existing O/W self-emulsifying systems, commonly used in food and pharmaceutical formulations 18,28,29 , could be used to easily incorporate avocado polyols. Supplementary Table 1 shows a list of formulations that were tested for self-emulsification.…”

Section: Sedds Development and Characterizationmentioning

confidence: 99%

Avocado-derived polyols for use as novel co-surfactants in low energy self-emulsifying microemulsions

Ahmed

Kermanshahi

Ghazani

et al. 2020

Sci Rep

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Avocado (Persea americana Mill.; Lauraceae) seed-derived polyhydroxylated fatty alcohols (PFAs) or polyols (i.e., avocadene and avocadyne) are metabolic modulators that selectively induce apoptosis of leukemia stem cells and reverse pathologies associated with diet-induced obesity. Delivery systems containing avocado polyols have not been described. Herein, natural surface active properties of these polyols are characterized and incorporated into self-emulsifying drug delivery systems (SEDDS) that rely on molecular self-assembly to form fine, transparent, oil-in-water (O/W) microemulsions as small as 20 nanometers in diameter. Mechanistically, a 1:1 molar ratio of avocadene and avocadyne (i.e., avocatin B or AVO was shown to be a eutectic mixture which can be employed as a novel, bioactive, cosurfactant that significantly reduces droplet size of medium-chain triglyceride O/W emulsions stabilized with polysorbate 80. In vitro cytotoxicity of avocado polyol-SEDDS in acute myeloid leukemia cell lines indicated significant increases in potency and bioactivity compared to conventional cell culture delivery systems. A pilot pharmacokinetic evaluation of AVO SEDDS in C57BL/6J mice revealed appreciable accumulation in whole blood and biodistribution in key target tissues. Lastly, incorporation of AVO in SEDDS significantly improved encapsulation of the poorly water-soluble drugs naproxen and curcumin. Avocados have been shown to be an exclusive source of unique long carbon chain (C 17 to C 21) polyhydroxylated fatty alcohols or polyols that possess anti-cancer, anti-inflammatory and anti-microbial properties 1-4. Previously, we demonstrated that avocatin B (AVO), a 1:1 mixture of two 17-carbon polyols (avocadyne and avocadene), target mitochondria and inhibit fatty acid oxidation (FAO) which selectively induces death in leukemia cells 5-8. More recently, avocadyne has been shown to exert potent immunomodulatory effects that impede dengue virus replication in vitro 9. Furthermore, our laboratory determined that AVO inhibited FAO in skeletal muscle and pancreatic β-cells reversing insulin resistance and restoring glucose tolerance in diet-induced obesity 10. The highly promising indications for avocado polyols in human disease and nutrition necessitate the complete characterization of their physicochemical properties and subsequent development of optimal formulations for future in vivo and clinical studies. To our knowledge, use of avocado polyols is prominent in topical cosmetic formulations described briefly in patent literature 11,12. This is the first report that avocadene and avocadyne possess unique physicochemical properties ideal for SEDDS applications. SEDDS comprise a mixture of oils, co-solvents, surfactants and co-surfactants that spontaneously self-assemble into oil-in-water (O/W) or water-in-oil (W/O) nano (~100-400 nm in diameter) or micro (<100 nm in diameter) emulsions 13. Surfactants delay droplet coalescence by reducing the surface free energy associated with the oil-water interface by creating a rigid, ...

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Section: Sedds Development and Characterizationmentioning

confidence: 99%

Avocado-derived polyols for use as novel co-surfactants in low energy self-emulsifying microemulsions

Ahmed

Kermanshahi

Ghazani

et al. 2020

Sci Rep

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“…Pharmaceutics 2020, 12, 365 4 of 57 increasing lipolysis by lipase [27,28]. For this, a high surfactant concentration is usually required to sufficiently stabilize the high surface area of the lipid-water interface.…”

Section: Conventional Solubilized Seddssmentioning

confidence: 99%

“…Another limitation of a conventional solubilized SEDDS is toxicity. It is desirable to create micro/nano-sized emulsion droplets and micelles to increase the surface area to volume ratio, thereby increasing lipolysis by lipase [27,28]. For this, a high surfactant concentration is usually required to Figure 1.…”

Section: Aim Of This Studymentioning

confidence: 99%

“…There are several well-demonstrated review papers about regulatory status. We suggest referring to those review papers to get closer to successful commercialization [22,28,29].…”

Section: Definition Of Su-seddssmentioning

confidence: 99%

“…Simplistically, this can be regarded as a drop in the free drug concentration in the GI fluid since most of the drug is solubilized in colloidal particles. Despite the reduction in free concentration owing to these drug-containing colloidal particles, drug absorption could potentially be maintained since the transfer from the solubilized reservoir to the free drug is rapidly equilibrated depending on drug absorption.Pharmaceutics 2020, 12, 365 4 of 57 increasing lipolysis by lipase [27,28]. For this, a high surfactant concentration is usually required to sufficiently stabilize the high surface area of the lipid-water interface.…”

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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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