title: Processing-induced-transformations (PITs) during direct compression: Impact of tablet composition and compression load on phase transition of caffeine.
abstract: In the pharmaceutical field, solid-state transitions that may occur during manufacturing of pharmaceuticals are of great importance. The phase transition of a model API, caffeine Form I (CFI), was studied during direct compression process by analysing the impacts of the operating conditions (process and formulation). This work is focused on two formulation parameters: nature of the diluent and impact of the caffeine dilution, and one process parameter: the compression pressure that may impact the phase transition of CFI. Tablets were made from pure CFI and from binary mixture of CFI/diluent (microcrystalline cellulose or anhydrous dicalcium phosphate). A kinetic study performed during six months helped to highlight the influence of these parameters on the CFI transition degree. Results showed a triggering effect of the direct compression process, transformation was higher in tablets than in uncompressed powders. Whatever the pressure applied, CFI transition degree was almost constant and uniformly occurring throughout the tablet volume. Nevertheless, several differences on the evolution of the CFI transition degree were observed between binary mixtures of CFI/diluent. An analysis of the transition mechanism with a stretched exponential law of the Johnson-Mehl-Avrami model shows that tableting accelerates the polymorphic transition without modifying its mechanism controlled by nucleation only.
authors: Univ Lyon, Universite Lyon 1, CNRS, UMR5007, LAGEP, 43 bd du 11 Novembre 1918, F-69622 Lyon, France.
authors: Audrey
authors: A
authors: Juban
authors: Univ Lyon, Universite Lyon 1, CNRS, UMR5007, LAGEP, 43 bd du 11 Novembre 1918, F-69622 Lyon, France.
authors: Stéphanie
authors: S
authors: Briançon
authors: Univ Lyon, Universite Lyon 1, CNRS, UMR5007, LAGEP, 43 bd du 11 Novembre 1918, F-69622 Lyon, France; LGPM, Laboratoire de Génie des Procédés et Matériaux, CentraleSupélec, Université Paris-Saclay, Grande Voie des Vignes, 92295 Châtenay-Malabry, France. Electronic address: francois.puel@centralesupelec.fr.
authors: François
authors: F
authors: Puel
mesh_terms: D002110:Caffeine / Q000737:chemistry*; D002482:Cellulose / Q000737:chemistry; D044367:Phase Transition; D011208:Powders; D011312:Pressure; D013314:Stress, Mechanical; D013607:Tablets
chemical_list: D011208:Powders; D013607:Tablets; D002110:Caffeine; D002482:Cellulose; C109691:microcrystalline cellulose
keywords: Anhydrous dicalcium phosphate (PubChem CID: 24441); Caffeine (PubChem CID: 2519); DSC; Direct compression; Johnson-Mehl-Avrami model; Microcrystalline cellulose (PubChem CID: 14055602); Polymorphic transformation; Processing induced transition (PITs); Tabletting