From Unwanted Annoyances to Oral Delivery Saviors: The Rollercoaster Journey of Amorphous Drugs

The benefits and disadvantages of amorphous drugs have been topics of discussion for nearly a century. In the post-World War II era when drug discovery burgeoned, amorphous drugs were largely regarded as unfavorable forms for commercial products. This sentiment began to change as the number of poorly water-soluble drugs, which targeted a broader range of disease states and emerged from high throughput screening assays, began to increase. The solubility advantage of amorphous drugs was long recognized at this juncture, but unease persisted over potential conversions back to the less soluble crystal form during product storage. Successful development of early amorphous products based on amorphous solid dispersion formulations, where a suitable polymer is molecularly mixed with the drug resulting in inhibition of drug crystallization, gradually mitigated concerns. This historical perspective of amorphous drugs provides an overview of timelines and key milestones and culminates by considering remaining challenges and the future outlook.