Self-emulsification of Lipidic Drug Delivery System in Pure Water and in Concentrated Glycerol Solution

Abstract

Self-emulsifying drug delivery systems (SEDDS), often intended for oral delivery, are normally explored in biorelevant aqueous media. The high complexity of these multi-component systems leaves the understanding of self-emulsification poor, hindering formulation rationalization. In this work, we aimed to fill this gap by studying the effects of glycerol on the self-emulsification of a ternary component formulation made of 20% w/w Tween 80, 15% w/w Span 80, and 65% w/w Captex 300 Low C6. The behavior of SEDDS in pure water and a binary mixture of water and glycerol (58.8% w/w) were investigated by optical microscopy, SAXS (small angle X-ray scattering), dynamic light scattering, and surface tension measurements. The presence of glycerol, at 58.8% w/w, altered the self-emulsification behavior by suppressing the formation of lamellar structures observed in the presence of water, reducing the droplet mean diameter from 0.2 to 0.1 μm and changing the mechanism of self-emulsification. As co-surfactant, glycerol may intercalate within the polyoxyethylene chains of the surfactant at the palisade layer, increasing the interface flexibility and expanding it. Since no free water is available at the investigated glycerol concentration, glycerol, which is also a co-solvent, may additionally modify long-range interactions by reducing Van-der-Waals attractions or giving rise to repulsive surface-solvent mediated forces of entropic origin. These effects could be exploited to rationalize SEDDS formulations, widening their use within the pharmaceutical industry.

Review of Crystallization in Nanoconfinement Created by Emulsions and Microemulsions for Pharmaceutical Applications

“…Solid lipid nanoparticles containing antioxidants and the methods to produce them were described by Ling et al Similar particles for the delivery of nutraceuticals has been described by others . Planchette and Mercuri described a process creating self-emulsifying nanosuspensions as drug delivery systems with nanoparticle sizes within the range of 10 to 1000 nm . The wide variety of nanoparticle systems for drug and nutraceutical delivery described in the patent literature suggests that these systems have many practical applications.…”

Experimental investigation on the properties of liquid film breakup induced by shock waves*

“…The reason is that the van der Waals force exists not only between water molecules and water molecules, but also between glycerol molecules and glycerol molecules, and more likely exists between water molecules and glycerol molecules. Planchette et al [34] found that, because no free water is available at the investigated glycerol concentration, glycerol, which is also a co-solvent, may additionally modify long-range interactions by reducing van der Waals attractions or giving rise to repulsive surface-solvent mediated forces of entropic origin. In this case, the van der Waals force of the mixture is significantly smaller than those between droplets of pure water or pure glycerol (99.5%).…”

Sistemas de entrega de fármacos autoemulsificables: una plataforma de desarrollo alternativa para la industria farmacéutica colombiana

“…Los tensioactivos son moléculas anfifílicas que generalmente son aplicadas en la estabilización de emulsiones/dispersiones que actúan como mediadores entre compuestos hidrofílicos e hidrofóbicos en las interfaces aceite-agua [60]. Estos logran disminuir la tensión interfacial y aumentar la flexibilidad en la interfaz, lo que permite la formación espontánea de la dispersión, además, producen una capa alrededor de las gotas de la dispersión que estabiliza la interface aceite-agua y proporciona una barrera mecánica para la coalescencia [109,110].…”

“…Los cotensioactivos penetran la monocapa del tensioactivo creando espacios vacíos entre las moléculas de este, proporcionando una fluidez adicional a la película interfacial lo que conlleva a una mejor emulsificación reduciendo el tamaño de gota y el índice de polidispersidad [94,96]. Generalmente, suele usarse la combinación de tensioactivos con valores de HLB altos y bajos para mejorar la habilidad de emulsificación del sistema [109,114].…”

“…Habitualmente, los cosolventes más utilizados corresponden a alcoholes o polioles de cadena corta [109]. Adicionalmente, la inclusión de cosolventes en la formulación de SEDDS permite una expansión en la región de autoemulsificación en la construcción de los diagramas de fase lo que puede significar una reducción en la concentración de tensioactivos disminuyendo la posibilidad de efectos adversos [46].…”