T.K. Law

The stabilization of w/o/w emulsions by interfacial interaction between albumin and non-ionic surfactants

Abstract The stability of w/o/w emulsions has been improved by means of interfacial interaction between Span 80 (sorbitan mono-oleate) and bovine serum albumin (BSA). The formation of an interfacial complex was demonstrated by the production of a visible film at the planar oil/water interface and by the increased stability of the w/o/w emulsions. The stability of each w/o/w emulsion was assessed in terms of the amount of internal aqueous phase remaining entrapped. This was dependent on the concentrations of both the Span 80 and the BSA, although increasing the BSA concentration above 0.2% only produced a minimal increase in stability. The release of sodium chloride from the internal aqueous phase and the changes in the physical structure of the w/o/w emulsions subjected to different osmotic pressure gradients were studied. Osmotic swelling of the internal aqueous phase induced thinning of the oil layer and explains the observed increase in the rate of solute release from the internal phase under high osmotic pressure gradients.

Stabilisation of w/o/w multiple emulsions by interfacial complexation of macromolecules and nonionic surfactants

Abstract A new approach to obtain stable w/o/w multiple emulsions has been developed; the basis is the interfacial interaction between a macromolecule, e.g. albumin or polyacrylic acid in the internal aqueous, and a lipophilic poloxamer surfactant in the dispersed oil phase. Lipophilic poloxamer surfactants of high molecular weight, e.g. Poloxamer 331, were preferable in forming a stable w/o and the subsequent w/o/w emulsions. Similarly, hydrophilic poloxamer surfactants of high molecular weight could enhance the stability of the w/o/w multiple emulsions when used to emulsify the initial w/o emulsions, e.g. poloxamer 403. A water soluble, internal marker, Sulphane Blue, was encapsulated within the emulsion droplets and the release rate studies were carried out. The results revealed that both the mass transfer rate and stability of the oil membrane could be influenced by the combination of external (secondary) hydrophilic surfactants used. The secondary surfactant affected release rate primarily by control of mass transfer through the oil liquid membrane. In optimising a stable multiple emulsion formulation, both the HLB (hydrophilic-lipophilic balance) values and surface activities of the surfactants have to be considered.

Nonaqueous foam structures from osmotically swollen w/o/w emulsion droplets

The inherent instability of w/o/w multiple emulsions can be partly overcome by the formation of a stable interfacial membrane through the interfacial interaction of a macromolecule such as bovine serum albumin in the aqueous phase and a lipophilic nonionic surfactant such as Poloxamer 331 in the oil phase of of the primary water/oil emulsion. A high-molecular-weight hydrophilic poloxamer (Poloxamer 403) used to form the multiple emulsion from this primary system was shown to strengthen the membrane so that it could withstand extensive thinning caused by the osmotically driven influx of water and swelling of the internal droplets. The oil-continuous stabilizing film at its thinnest can only be observed under phase-contrast or dark-field illumination. Single droplets carrying such a thin oil membrane were stable for several weeks. After equilibration of osmotic pressure across the membrane, i.e., after storage, the membrane appeared to have sufficient elasticity that it could respond to osmotic changes in the external aqueous phase. The new structures formed in these osmotically swollen systems are possibly analogs of aqueous foam bubbles in air and are the biliquid foams or “aphrons” described by F. Sebba (J. Colloid Interface Sci.40, 468, 1972).

Some chemically modified poloxamer hydrogels: preparation, morphology and swelling properties

Abstract Polymerizable diacryloyl derivatives of a series of commercial poly(oxyethylene)-poly(oxypropylene)-poly(pxyethylene) block copolymeric surfactants have been prepared and polymerized to form cross-linked hydrogels whose properties can be varied by controlling the proportions of hydrophilic and hydrophobic monomers (e.g. Pluronic F68, poloxamer 188 and Pluronic L61, poloxamer 181). Morphology and spherulite formation of the hydrogels prepared from pure monomer and mixtures of the modified monomers were studied using optical and scanning electron microscopy, Spherulite formation in these mixtures was used as a probe of mixing compatibility and the imbibition of water, acting as a selective solvent, revealed different states of heterogeneity in the various cross-linked gels. Swelling of the gels in aqueous media increased in a non-liner fashion with increasing proportion of the modified, more hydrophilic, poloxamer 188 in the gel.

Some chemically modified poloxamer hydrogels: controlled release of prostaglandin-E2 and testosterone

Abstract Cross-linked, swelling hydrogels derived from the acryloyl derivatives of poloxamer co-polymeric surfactants have been prepared and their morphology and swelling properties described previously. Using modified pure poloxamer 188 (Pluronic F68) to prepare the hydrogels (the system which gives release rates closest to the desirable time-independent, zero-order kinetics) the release of prostaglandin-E 2 (PGE 2 ) and testosterone has been studied. PGE 2 release was very closely described by the swelling controlled release model with a value of n = 0.71 and a time for 60% release of 670 min (at 37°C). Testosterone release, however, more closely followed Higuchi (or diffusion-controlled) release kinetics with a t 60% value of 56 h, probably reflecting the much lower solubility of testosterone in both water and the swollen, hydrated outer gel matrix.

Stabilisation of emulsions by interfacial polymerisation of poloxamer surfactant derivatives

A method of increasing the stability ofo/w emulsions and providing a potential additional barrier to drug release from the oil droplets is described. Diacryloyl derivatives of non-ionic block copolymers (poloxamers) have been used to stabilise isopropyl myristate in water emulsions. Cross-linking of these stabilisers at the oil-water interface produces a polymeric region which increases the stabilityo/w emulsions to centrifugation and of thew/o emulsions to creaming.

Aggregation and gelation of a polymerisable diacryloyl derivative of poloxamer 407

Abstract The diacryloyl derivative of poloxamer 407 has been prepared and its aggregation and gelation properties in solution studied. With increasing temperature over the range 25–50 °C the hydrodynamic diameter of aggregates decreased from 274 to 69 nm, in contrast to unmodified poloxamer 407 where the hydrodynamic size remains constant. Hydrogels can be formed by polymerisation of the diacryloyl derivative in aqueous solution: such hydrogels can absorb water up to 1600% of their initial dry gel weight. Ethanol inhibits gelation and this has been shown to be due to the fact that only small, possibly monomolecular, micelles are formed in such mixed solvent systems.

Surfactant-Mediated Transport Through Liquid Hydrocarbon Membranes

Water flux through layers of hexadecane and isopropyl myristate has been measured in the presence of non-ionic surfactants. In the absence of surfactant the diffusion coefficient for water through a layer of hexadecane is 4.10 x 10−5 cm2s−1 and a permeability coefficient of 8.29 x 10−9 cm s−1 through a 0.267 cm layer of hexadecane was calculated. Water flux and the permeability coefficient of layers of hexadecane and isopropyl myristate increased on addition of sorbitan mono-oleate (Span 80). The effect of a combination of hydrophilic and lipophilic surfactants in the oil layers on water flux has been studied. At a constant Span 80 concentration, increasing concentration of either sorbitan poly-(oxyethylene) oleate (Tween 80) or sorbitan poly-(oxyethylene) tri-oleate (Tween 85) increased water flux.

Thin Films of Non-Ionic Poloxamer Surfactants: Thinning and Polymerisation of Poloxamer 407

Thin liquid draining films of poloxamer 407 block co-polymeric surfactant solutions have been investigated using reflected laser light intensity to determine film thicknesses. Only in IM NaCl do stable thin films form. A discontinuous stepwise thinning has been found in these systems with metastable film thicknesses of, for example, 80nm and 58nm forming prior to forming a final stable film thickness of 28nm.