Abstract
The aim of this study was to investigate the fate and the impact of cosolvents in self-emulsifying drug delivery systems (SEDDS). Three different SEDDS comprising the cosolvents DMSO (FD), ethanol (FE), and benzyl alcohol (FBA) as well as the corresponding formulations without these cosolvents (FD0, FE0, and FBA0) were developed. Mean droplet size, polydispersity index (PDI), ζ potential, stability, and emulsification time were determined. Cosolvent release studies were performed via the dialysis membrane method and Taylor dispersion analysis (TDA). Furthermore, the impact of cosolvent utilization on payloads in SEDDS was examined using quinine as a model drug. SEDDS with and without a cosolvent showed no significant differences in droplet size, PDI, and ζ potential. The emulsification time was 3-fold (FD0), 80-fold (FE0), and 7-fold (FBA0) longer due to the absence of the cosolvents. Release studies in demineralized water provided evidence for an immediate and complete release of DMSO, ethanol, and benzyl alcohol. TDA confirmed this result. Moreover, a 1.4-fold (FD), 2.91-fold (FE), and 2.17-fold (FBA) improved payload of the model drug quinine in the selected SEDDS preconcentrates was observed that dropped after emulsification within 1–5 h due to drug precipitation. In parallel, the quinine concentrations decreased until reaching the same levels of the corresponding SEDDS without cosolvents. Due to the addition of hydrophilic cosolvents, the emulsifying properties of SEDDS are strongly improved. As hydrophilic cosolvents are immediately released from SEDDS during the emulsification process, however, their drug solubilizing properties in the resulting oily droplets are very limited.
Highlights
One of the most promising tools for oral delivery of poorly water-soluble drugs are lipid-based formulations (LBF)
The benefit of self-emulsifying drug delivery systems (SEDDS) is mainly based on the comparatively high solubility of drugs in the oily droplets during their transit through the gastrointestinal tract.[6−8] it is required to dissolve drug candidates in the lipid phase of the formulation in order to achieve sufficiently high payloads providing solubility until absorption.[9−11] Lipid-based excipients commonly used in SEDDS include vegetable oils and their derivatives, which are effortlessly emulsified by surfactants and cosurfactants.[12,13]
In order to develop suitable SEDDS for cosolvent release studies, nanoemulsion areas of the selected components have been evaluated by pseudoternary phase diagram construction
Summary
One of the most promising tools for oral delivery of poorly water-soluble drugs are lipid-based formulations (LBF). Solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), nanoemulsions, and self-emulsifying drug delivery systems (SEDDS) offer improved oral bioavailability for incorporated lipophilic drugs.[1] Among LBFs, in particular, SEDDS are of high industrial relevance In recent years, these systems have been frequently utilized to enhance oral bioavailability of poorly water-soluble drugs by forming colloidal systems after self-emulsification.[2,3] many examples proving oral bioavailability enhancement of drugs incorporated into SEDDS can be found in literature and on the global market.[4,5] The benefit of SEDDS is mainly based on the comparatively high solubility of drugs in the oily droplets during their transit through the gastrointestinal tract.[6−8] it is required to dissolve drug candidates in the lipid phase of the formulation in order to achieve sufficiently high payloads providing solubility until absorption.[9−11] Lipid-based excipients commonly used in SEDDS include vegetable oils and their derivatives, which are effortlessly emulsified by surfactants and cosurfactants.[12,13] In order to provide sufficient drug solubility in SEDDS, hydrophilic organic solvents such as glycerol (log P = −1.76), dimethyl sulfoxide (DMSO) (log P = −1.35), ethanol (log P = −0,31), isopropanol (log P = 0.05), or benzyl alcohol (BA) (log P = 1.1) are utilized.[2,6] With the aid of these cosolvents, it is possible to dissolve most drugs in SEDDS preconcentrates. A fast release of cosolvents from SEDDS and the drop in drug solubility within the oily droplets can be anticipated, the release of such
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