title: Formation, Physicochemical Characterization, and Thermodynamic Stability of the Amorphous State of Drugs and Excipients.
abstract: Drugs and excipients used for pharmaceutical applications generally exist in the solid (crystalline or amorphous) state, more rarely as liquid materials. In some cases, according to the physicochemical nature of the molecule, or as a consequence of specific technological processes, a compound may exist exclusively in the amorphous state. In other cases, as a consequence of specific treatments (freezing and spray drying, melting and co-melting, grinding and compression), the crystalline form may convert into a completely or partially amorphous form. An amorphous material shows physical and thermodynamic properties different from the corresponding crystalline form, with profound repercussions on its technological performance and biopharmaceutical properties. Several physicochemical techniques such as X-ray powder diffraction, thermal methods of analysis, spectroscopic techniques, gravimetric techniques, and inverse gas chromatography can be applied to characterize the amorphous form of a compound (drug or excipient), and to evaluate its thermodynamic stability. This review offers a survey of the technologies used to convert a crystalline solid into an amorphous form, and describes the most important techniques for characterizing the amorphous state of compounds of pharmaceutical interest.
authors.affiliation: School of Pharmacy, University of Camerino, 1 Via S. Agostino, Camerino, 62032, Italy. piera.dimartino@unicam.it.
authors.forename: Piera Di
authors.initials: PD
authors.lastname: Martino
authors.forename: Federico
authors.initials: F
authors.lastname: Magnoni
authors.forename: Dolores Vargas
authors.initials: DV
authors.lastname: Peregrina
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Gigliobianco
authors.forename: Roberta
authors.initials: R
authors.lastname: Censi
authors.forename: Ledjan
authors.initials: L
authors.lastname: Malaj
mesh_terms: D002627:Chemistry, Physical; D003460:Crystallization; D004339:Drug Compounding; D004355:Drug Stability; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D004364:Pharmaceutical Preparations