Abstract
Poorly water-soluble drugs pose a significant challenge to developability due to poor oral absorption leading to poor bioavailability. Several approaches exist that improve the oral absorption of such compounds by enhancing the aqueous solubility and/or dissolution rate of the drug. These include chemical modifications such as salts, co-crystals or prodrugs and physical modifications such as complexation, nanocrystals or conversion to amorphous form. Among these formulation strategies, the conversion to amorphous form has been successfully deployed across the pharmaceutical industry, accounting for approximately 30% of the marketed products that require solubility enhancement and making it the most frequently used technology from 2000 to 2020. This article discusses the underlying scientific theory and influence of the active compound, the material properties and manufacturing processes on the selection and design of amorphous solid dispersion (ASD) products as marketed products. Recent advances in the analytical tools to characterize ASDs stability and ability to be processed into suitable, patient-centric dosage forms are also described. The unmet need and regulatory path for the development of novel ASD polymers is finally discussed, including a description of the experimental data that can be used to establish if a new polymer offers sufficient differentiation from the established polymers to warrant advancement.
Highlights
The oral route of drug administration is regarded as the most preferred route for medicines, with more than 85% of drugs sold around the world being administered orally.In this context, the properties of a drug molecule that govern oral absorption are critical to its development
Various electron microscopic techniques can enable the detection of crystals in amorphous solid dispersion (ASD): Scanning Electron Microscopy (SEM) images with high magnifications that project the surface texture in great detail provide a good method for observation of potential crystallization; when upgraded with the Energy-dispersive X-ray spectroscopy (EDS), the grouping of elemental composition can further aid the detection of crystals [60]
Spray drying (SD) and fluid-bed layering (FBL) technologies based on the principle of solvent evaporation and hot-melt extrusion (HME) technology based on fusion/melting are scalable processes commonly employed in the pharmaceutical industry for commercialscale manufacturing of ASD, with SD and HME accounting for more than 60% of marketed products as seen in Figure while, Figure shows the various stabilization polymers used in Marketed ASD products
Summary
The oral route of drug administration is regarded as the most preferred route for medicines, with more than 85% of drugs sold around the world being administered orally. In a comparison of solubility of 200 oral drugs of various origin as seen, 40–45% were very slightly soluble to practically insoluble, representing 33% of drugs listed in the US Pharmacopeia and 75% of compounds under development and 90% of new chemical entities were re-. Pharmaceutics 2021, 13, 1682 slightly soluble to practically insoluble, representing 33% of drugs listed in the US Pharmacopeia and 75% of compounds under development and 90% of new chemical entities garded as poorlyassoluble. For poorly soluble drugs, increasing aqueous solubility and the surface area are. Salt forms of poorly soluble acidic or basic drugs (via ionization or dissociation). Chemical functional groups such as esters for metabolic conversionReduced lipophilicity and optimized ADME [22,23].
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