Microwave-induced in situ amorphization: mechanistic basis, formulation principles, and translational perspective

Although amorphous solid dispersions (ASDs) improve the oral delivery of drugs with poor water-solubility, their broader application is limited by the physical instability of the amorphous state and challenges associated with the downstream processing of metastable materials. Microwave-induced in situ amorphization provides an alternative route to ASD formation by maintaining the drug in a crystalline form before microwave treatment and inducing amorphous conversion within the prepared dosage form. This review traces the development of the approach and integrates mechanistic understanding with the formulation and process factors governing its performance. Available evidence indicates that amorphization proceeds primarily through drug dissolution into a transiently mobile carrier phase, rather than direct melting of the crystalline drug. Successful conversion and retention of the amorphous state require coordinated dielectric activation, carrier mobility, and post-amorphization stabilization. The overall performance depends on drug and excipient properties, moisture content, compact structure, and microwave conditions. To facilitate practical implementation, recent formulation strategies have broadened the available activation routes and reduced reliance on external humidity conditioning. Microwave-induced in situ amorphization may therefore complement conventional ASD manufacturing, particularly when storage or downstream processing of metastable amorphous systems remains challenging.