Review: physical chemistry of solid dispersions

Abstract

Objectives With poorly soluble drug candidates emerging in the drug discovery pipeline, the importance of the solid dispersion formulation approach is increasing. This strategy includes complete removal of drug crystallinity, and molecular dispersion of the poorly soluble compound in a hydrophilic polymeric carrier. The potential of this technique to increase oral absorption and hence bioavailability is enormous. Nevertheless, some issues have to be considered regarding thermodynamic instability, as well in supersaturated solutions that are formed upon dissolution as in the solid state. Key findings After a brief discussion on the historical background of solid dispersions and their current role in formulation, an overview will be given on the physical chemistry and stability of glass solutions as they form supersaturated solutions, and during their shelf life. Conclusions Thorough understanding of these aspects will elicit conscious evaluation of carrier properties and eventually facilitate rational excipient selection. Thus, full exploitation of the solid dispersion strategy may provide an appropriate answer to drug attrition due to low aqueous solubility in later stages of development.

Physicochemical Evaluation and Developability Assessment of Co-amorphouses of Low Soluble Drugs and Comparison to the Co-crystals

“…4,5) In many cases, an amorphous drug is formulated by solid dispersion with hydrophilic polymers to improve the amorphous drug stability. [6][7][8] The complex formed with polymers can prevent the drug's crystallization and maintain the physical stability of the amorphous state. Generally, weak interactions cannot sufficiently stabilize amorphous drugs.…”

Challenges and Strategies in Thermal Processing of Amorphous Solid Dispersions: A Review

“…A number of solubility-enhancing strategies have been investigated over the last few decades to enable oral delivery of these drugs (4,5). Examples include the use of salts or cocrystals (6), lipid vehicles (7), cyclodextrins (8), micronization and nanoparticle engineering (9,10), and amorphous solid dispersions (11)(12)(13).…”

“…The softened material is then forced through a die for shaping and downstream processing. In processing ASDs, the drug is melted or solubilized in the polymeric carrier and the rapid cooling and high viscosity results in a thermodynamically or kinetically stabilized amorphous dispersion (11). The Meltrex® platform commercialized by Soliqs and AbbVie is perhaps the most well-known example of HME-enabled products in the pharmaceutical industry, including the solid oral dosage forms of Kaletra® and Norvir® for treatment of HIV (34), the recently approved Viekirax® for treatment of HCV (35,36), and other products in development for oncology indications (37).…”

Comparison Between Hot-Melt Extrusion and Spray-Drying for Manufacturing Solid Dispersions of the Graft Copolymer of Ethylene Glycol and Vinylalcohol

“…The choice of carrier has a tremendous impact on the success rate of the solid dispersion strategy. The most important carrier properties were recently reviewed by Janssens and Van den Mooter (1). Besides safety, properties such as a high glass transition temperature (T g ), the presence of functional groups enabling interactions with the dispersed drug, solubility and the possibility to maintain drug supersaturation in the gastrointestinal tract are considered important characteristics.…”