Gelucire® 44/14 – Self-emulsifying excipient for solubility and oral bioavailability enhancement

Product description

Gelucire® 44/14 is a non-ionic water dispersible surfactant recommended for use in lipid-based formulations to increase the aqueous solubility and oral bioavailability of poorly water soluble drugs.

A multi-component excipient

Gelucire® 44/14 is obtained by an alcoholysis reaction between coconut oil and polyethylene glycol-32 (PEG-32) under controlled conditions. It consists of glycerides and PEG esters of fatty acids of varying chain length. (Figure 1).

Main physicochemical properties of Gelucire® 44/14

Melt characteristics

Gelucire® 44/14 by Gattefossé presents a broad endotherm ranging from 10 to 45°C, with an onset melting temperature of about 38°C and a peak melting temperature of about 43°C (blue line, Figure 2). This thermal behaviour is related to composition: the mono-, di- and triglyceride fraction melts first (orange line, Figure 2), followed by the PEG-ester fraction (green line, Figure 2).

Did you know?
Gelucire® 44/14 melting begins as low as 10°C,
meaning that at 20 – 25°C a fraction of Gelucire® 44/14
is already liquid. This is why the product is described as
‘semi-solid’ and is supplied in block form.

Product functionality

Spontaneous self-emulsification in aqueous media

Gelucire® 44/14 is a self-emulsifying system: upon contact with aqueous / digestive media it spontaneously forms a fine dispersion. The different components self-assemble as a function of their affinity for water: PEGs are water soluble, PEG esters and monoglycerides are amphiphilic and di- and triglycerides are hydrophobic.

At a concentration above the CMC (≈0.07 g/L), self-assembly results in the formation of micelles of about 10-100 nm mean diameter measured by Diffraction Light Scattering (Figure 3).

The fate of Gelucire® 44/14 in the gastro-intestinal tract: self-emulsification, digestion and absorption

Handling and processing

Handling a semi-solid excipient

Gelucire® 44/14 is composed of several fractions with different densities and crystallization temperatures. After synthesis, the molten excipient is hot filled in the container. During cooling and crystallization the product stratifies resulting in a non-homogenous composition in the container. Therefore, the entire product in the original container must be fully melted at 70 – 80°C and homogenized before sampling and use (Figure 5).

Lipids are naturally sensitive to oxidation and hydrolysis. Gelucire® 44/14 industrial containers are opaque to light, filled under nitrogen and tightly sealed.

Correct handling helps to preserve product integrity:
• Melt the product in a dry oven, an incubator or a microwave oven (do not use a water bath).
• After use, flush the container with nitrogen and seal tightly.
• Store the container at room temperature.

A detailed product handling sheet is available on request

Measuring API solubility in Gelucire® 44/14

The simplest method is to measure API solubility in molten Gelucire® 44/14 at about 50°C. However, the elevated temperature will generally result in an over-estimation of drug solubility. The most accurate method consists in measuring the solubility of API by Differential Scanning Calorimetry (DSC), coupled with hot stage microscopy. A detailed protocol can be provided upon request.

Processing

Gelucire® 44/14 can be used in a variety of processes however, capsule molding by filling with a molten liquid or low viscosity formulation is the most common and straightforward. Other processes such as solid dispersion by fusion, evaporation or supercritical CO2 methods, spray drying, melt granulation, melt extrusion and 3D printing are reported in the scientific literature.

Download the full brochure on “Gelucire® 44/14 brochure” here

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Source: Gattefossé brochure “Gelucire® 44/14 brochure”

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