The Coming of Age of Amorphous Solid Dispersions

Although the majority of new drug candidates suffer from poor solubility and bioavailability, oral solid dosage forms remain the preferred route of administration due to their ease of use and convenience for patients and caregivers. In recent years, numerous drugs formulated as amorphous solid dispersions (ASDs) have been successfully commercialized, confirming the effectiveness of these technologies for enhancing the dissolution of challenging APIs.

A pharma’s Almanac Article – Oct 28, 2018 by Márcio Temtem, Ph.D. , Director for Drug Product Development, Hovione

Addressing Solubility Issues

Lead optimization during drug development does not typically address dissolution and bioavailability performance under physiologic conditions. As a result, a large percentage of pipeline candidates exhibit poor water solubility and low bioavailability. The challenge is to develop formulations and delivery mechanisms for these drug substances that enable oral administration, which remains the most desirable dosage form due to its generally lower cost of production, the preference of patients and caregivers for oral medications and overall higher compliance rates.

Benefits of ASDs

Enhancement of dissolution, solubility and bioavailability for poorly soluble APIs can be achieved using a number of different approaches, including particle size reduction (e.g., micronization and nanomilling), salt or cocrystal formation, lipid-based self-emulsification and the formation of ASDs.

For many poorly soluble drugs, preparation in an amorphous rather than a crystalline state can lead to improved dissolution profiles and enhanced bioavailability, as amorphous compounds lack long-range order. However, amorphous compounds are unstable. It is therefore necessary to form solid dispersions of amorphous APIs in polymeric matrices to improve their stability.  Once an ASD reaches the intestine, the API is released in a supersaturated concentration. It has been reported that over 80% of ASDs offer improved bioavailability.

A key advantage of ASDs is the ability to provide the final drug product in the form of a tablet or capsule — the most common oral dosage forms. In addition, compared with lipid-based systems, ASDs allow the formulation of drug products with much higher dosage levels. Lipid-based formulations typically contain no more than 100 mg of API, whereas ASDs have much higher API-to-polymer ratios and loadings of as much as 300–400 mg of active ingredient. Higher dosage formulations can benefit patients through reduced dosing frequencies and pill burdens.

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