Novel self-nanoemulsifying self-nanosuspension (SNESNS) for enhancing oral bioavailability of diacerein: Simultaneous portal blood absorption and lymphatic delivery

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Date

2015

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Journal ISSN

Volume Title

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Article

Publisher

Elsevier

Series Info

International Journal of Pharmaceutics
490

Abstract

The 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.

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Scopus

Keywords

Blocked chylomicron flow, Diacerein, Lymphatic delivery, Portal absorption, Self-nanoemulsifying self-nanosuspension, SNESNS, chylomicron, diacerein, phosphate buffered saline, rhein, surfactant, water, anthraquinone derivative, diacerein, drug carrier, emulsion, nanoparticle, rhein, surfactant, suspension, agitation, Article, drug absorption, drug bioavailability, drug blood level, drug delivery system, drug elimination, drug half life, drug solubility, drug synthesis, elimination rate constant, erosion, in vitro study, in vivo study, lymph vessel, maximum plasma concentration, nanoemulsion, particle size, pH, priority journal, suspension, time to maximum plasma concentration, transmission electron microscopy, zeta potential, administration and dosage, animal, bioavailability, chemistry, classification, drug delivery system, emulsion, male, medicinal chemistry, oral drug administration, pharmacokinetics, procedures, rat, solubility, suspension, Wistar rat, Administration, Oral, Animals, Anthraquinones, Biological Availability, Chemistry, Pharmaceutical, Drug Carriers, Drug Delivery Systems, Emulsions, Male, Nanoparticles, Particle Size, Rats, Rats, Wistar, Solubility, Surface-Active Agents, Suspensions

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