title: Water-mediated solid-state transformation of a polymorphic drug during aqueous-based drug-layer coating of pellets.
abstract: During aqueous drug-layer coating, drug substance(s) are exposed to water and elevated temperatures which can lead to water-mediated process induced transformations (PITs). The effects of aqueous drug-layer coating of pellets (Cellets(®)) on the anhydrous piroxicam, PRX, were investigated in the miniaturized coating equipment and with free films. Hydroxypropyl methylcellulose (HPMC) was used as a carrier coating polymer. Free films were prepared by using an in-house small-scale rotating plate system equipped with an atomization air nozzle. Raman spectroscopy, X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) were used to characterize the solid-state properties and surface morphology of the pellets and free films. The results showed that anhydrous PRX form I (AH) and monohydrate (MH) were stable during drug-layer coating, but amorphous PRX in solid dispersion (SD) crystallized as MH already after 10 min of coating. Furthermore, the increase in a dissolution rate was achieved from the drug-layer coated inert pellets compared to powder forms. In conclusion, water-mediated solid-state PITs of amorphous PRX is evident during aqueous-based drug-layer coating of pellets, and solid-state change can be verified using Raman spectroscopy.
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Tartu, Nooruse 1, 50411 Tartu, Estonia. Electronic address: andres.lust@ut.ee.
authors.forename: Andres
authors.initials: A
authors.lastname: Lust
authors.forename: Satu
authors.initials: S
authors.lastname: Lakio
authors.forename: Julia
authors.initials: J
authors.lastname: Vintsevits
authors.forename: Jekaterina
authors.initials: J
authors.lastname: Kozlova
authors.forename: Peep
authors.initials: P
authors.lastname: Veski
authors.forename: Jyrki
authors.initials: J
authors.lastname: Heinämäki
authors.forename: Karin
authors.initials: K
authors.lastname: Kogermann
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D004339:Drug Compounding / Q000379:methods; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D010894:Piroxicam / Q000737:chemistry*; D033362:Powder Diffraction; D012995:Solubility; D013059:Spectrum Analysis, Raman; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D014867:Water; D010894:Piroxicam; D065347:Hypromellose Derivatives; D008747:Methylcellulose
keywords: Drug-layer coating; Hydrate formation; Pellet; Piroxicam; Process induced transformation; Raman spectroscopy