A review on stabilization mechanism of amorphous form based drug delivery system

Drug delivery systems utilizing the amorphous form of the drug are receiving considerable attention for improving the solubility and dissolution properties of poorly water-soluble drugs. However, the inherent high free energy of the amorphous form also makes it prone for reverting to a stable crystalline form and thus losing the advantage of high solubility and better dissolution properties. Polymeric amorphous solid dispersion (PASD), co-amorphous systems (drug-drug and drug-small molecules excipient), and polymeric amorphous salts are some of the most explored formulation approaches that use the amorphous form of the drug to improve the solubility. The present review article summarises the various mechanisms mentioned in the literature for stabilizing the amorphous form of the drug for different formulations. The present review article also elaborated the differences and similarities among various amorphous form-based dosage forms in terms of the stabilization mechanism, the excipients used to prepare critical limitations, and unique advantages. Being a complex system, the stabilization of the amorphous form within the various formulations does not follow a single mechanism, which is why the same formulation approach can have different stabilization mechanisms depending on the physicochemical properties of the drug and excipients. An increase in the glass transition temperature, attractive forces generated due to molecular-level interaction between drug and excipient, and a reduction in the molecular mobility of the drug molecules are some of the main mechanisms mentioned in the literature for stabilizing the amorphous form of the drug.