El-Laithy H.M.Basalious E.B.El-Hoseiny B.M.Adel M.M.Department of Pharmaceutics and Industrial PharmacyFaculty of PharmacyCairo UniversityCairoEgypt; Department of Pharmaceutics and Industrial PharmacyFaculty of PharmacyOctober University for Modern Sciences and Arts (MSA)CairoEgypt; Duuepartment of PharmaceuticsNational Organization for Drug Control and ResearchCairoEgypt2020-01-092020-01-0920153785173https://doi.org/10.1016/j.ijpharm.2015.05.039PubMed ID 26002566https://t.ly/1VM95ScopusThe application of self-nanoemulsified drug delivery system (SNEDDS) to improve bioavailability of diacerein (D) has been hampered by its large dose and limited solubility. This work aimed to prepare diacerein loaded self nanoemulsifying self nanosuspension (D-SNESNS) containing high drug load. D-SNESNS was prepared by homogenizing D into Maisine-based SNEDDS that gave the highest drug solubility. D-SNESNS was evaluated for particle size, zeta potential and in vitro dissolution. Significant increase of D solubility was observed from D-SNESNS (?309 ?g/mL) than traditional SNEDDS (?162 ?g/mL) due to the spontaneous simultaneous formation of nanoemulsion and nanosuspension (top-down approach). When exposed to water with mild agitation, the drug microparticles in D-SNESNS are temporarily surrounded by unsaturated aqueous layer (containing optimum concentrations of surfactant and co-solvent) that facilitates the erosion of the suspended drug particles into nanosized ones. Nanoemulsion-based nanosuspension (NENS) was confirmed using transmission electron microscopy and particle size analysis. D-SNESNS equivalent to 50 mg D exhibited complete and very rapid dissolution after 15 min in phosphate buffer pH 6.8 due to the existence of D as solubilized molecules inside nanoemulsion globules and nanosized suspended drug particles forming D-NENS. The relative bioavailabilities of rhein from D-SNESNS in rats with normal and blocked chylomicron flow were about 210% and 164%, respectively in comparison to aqueous D suspension. The significant increase in the dissolution, portal absorption and lymphatic delivery of D propose that SNESNS could be promising to improve oral bioavailability of poorly water soluble drugs that have limited drug load in SNEDDS. 2015 Elsevier B.V. All rights reserved.EnglishBlocked chylomicron flowDiacereinLymphatic deliveryPortal absorptionSelf-nanoemulsifying self-nanosuspensionSNESNSchylomicrondiacereinphosphate buffered salinerheinsurfactantwateranthraquinone derivativediacereindrug carrieremulsionnanoparticlerheinsurfactantsuspensionagitationArticledrug absorptiondrug bioavailabilitydrug blood leveldrug delivery systemdrug eliminationdrug half lifedrug solubilitydrug synthesiselimination rate constanterosionin vitro studyin vivo studylymph vesselmaximum plasma concentrationnanoemulsionparticle sizepHpriority journalsuspensiontime to maximum plasma concentrationtransmission electron microscopyzeta potentialadministration and dosageanimalbioavailabilitychemistryclassificationdrug delivery systememulsionmalemedicinal chemistryoral drug administrationpharmacokineticsproceduresratsolubilitysuspensionWistar ratAdministration, OralAnimalsAnthraquinonesBiological AvailabilityChemistry, PharmaceuticalDrug CarriersDrug Delivery SystemsEmulsionsMaleNanoparticlesParticle SizeRatsRats, WistarSolubilitySurface-Active AgentsSuspensionsArticlehttps://doi.org/10.1016/j.ijpharm.2015.05.039PubMed ID 26002566