Using Polymers to Enhance Solubility of Poorly Soluble Drugs

The authors demonstrate how melt-extrusion and spray-drying methods can help to prepare solid dispersions of poorly soluble drugs using Eudragit polymers.
Apr 01, 2009
Volume 2009 Supplement, Issue 1

The number of poorly soluble drugs continues to increase. Forty percent of drugs currently on the market exhibit poor solubility, and 90% of active ingredients in development are poorly soluble (1). The interest in finding methods to increase solubility and dissolution rate is therefore growing. Industry uses various approaches to achieve these goals, many of which can be found in the literature.

Some methods manipulate the structure of the drug (e.g., they incorporate certain groups to generate a prodrug or the creation of different salts with higher solubility) (2). Other methods are physical such as decreasing the drug's particle size (e.g., micronization or nanosizing, crystal habit modification, complexation with cyclodextrins, generation of polymorphic forms or solubilization) (3). The most widely used approach is to form solid dispersions of the drug in a carrier, where the drug is present as amorphous or crystalline regions in a carrier, or—more preferable with respect to stability—the drug is dissolved molecularly in the polymer. In either case, solubility can be enhanced because there is no lattice energy to overcome to dissolve the drug. After the carier is dissolved, the drug is released to media already in a dissolved state. Besides other polymers, polymethacrylates such as Eudragit (Evonik Röhm GmbH, Darmstadt, Germany) are amorphous and more ideal for preparing solid dispersions.

Solid dispersions can be prepared using various techniques. Among these, spray-drying and melt extrusion have proved to enhance solubility. Both techniques have advantages as well as limitations. In the case of a drug with a high melting point, spray-drying is the method of choice because the temperature applied in the melt extruder is limited by the carriers' thermostability. Another limitation to melt extrusion is its application for temperature-sensitive drugs. In these cases, spray-drying could be better applied. One limitation to spray-drying is that, in some cases, there is no solvent available to dissolve the polymer and the drug. In this situation, melt extrusion has an obvious advantage. Organic solvents can lead to problems such as residual solvents in the product, lack of security during production, and environmental issues.

A previous article described the increase in dissolution from melt extrudates containing Eudragit E, Eudragit NE 30D, and felodipine (4). Eudragit NE 30D is a water-insoluble polymer conventionally used for sustained-release applications in coatings, matrix systems, and melt extrusion. In small portions, Eudragit NE 30D can be used as stabilizing agent. It swells and is dispersed as fine particles in the media, seperating the drug particles from each other and hindering precipitation.

This article compares these results with a similar formulation, prepared by spray-drying. The authors discuss how melt extrusion and spray-drying can be used to prepare solid dispersions of poorly soluble drugs with Eudragit polymers. These solid dispersions show comparable results in dissolution rate, X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC).

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