title: Polymorphic transformation of anhydrous caffeine under compression and grinding: a re-evaluation.
abstract: Polymorphic transformations that may occur during mechanical treatment are of great interest for the production of pharmaceutical solids. Anhydrous caffeine is a well-known example of such transformations but a careful reading of the already existing literature shows that published results are contradictory. In this study, both forms of caffeine, form I and form II, respectively metastable and stable at ambient pressure and temperature, were submitted to compression in an instrumented alternative press and to grinding, and were studied before and after treatment by X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC). Compression experiments showed no changes of form II during compression, whereas form I was partially transformed into form II. Nevertheless, this transformation did not happen immediately. Form II appeared after a kinetically slow transformation and was clearly detectable only after a few days, fact that was never mentioned by previous authors. Same phenomenon was observed after the grinding of form I but also after an extensive grinding of form II. DSC and XRPD measurements indicated that polymorphic transformation did not happen directly, but that a new intermediate form was obtained after mechanical treatment, which slowly turned into form II within a few days.
authors.affiliation: EA 401 Matériaux et Santé, UFR de Pharmacie, Université Paris-sud 11, Châtenay Malabry Cedex, France. Vincent.mazel@u-psud.fr
authors.forename: Vincent
authors.initials: V
authors.lastname: Mazel
authors.forename: Céline
authors.initials: C
authors.lastname: Delplace
authors.forename: Virginie
authors.initials: V
authors.lastname: Busignies
authors.forename: Vincent
authors.initials: V
authors.lastname: Faivre
authors.forename: Pierre
authors.initials: P
authors.lastname: Tchoreloff
authors.forename: Najet
authors.initials: N
authors.lastname: Yagoubi
mesh_terms: D002110:Caffeine / Q000737:chemistry / Q000302:isolation & purification*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004355:Drug Stability; D007536:Isomerism; D008855:Microscopy, Electron, Scanning; D033362:Powder Diffraction; D011208:Powders / Q000737:chemistry / Q000302:isolation & purification; D011312:Pressure
chemical_list: D011208:Powders; D002110:Caffeine