Water-mediated solid-state transformation of a polymorphic drug during aqueous-based drug-layer coating of pellets

• Published in: International journal of pharmaceutics Vol. 456; no. 1; pp. 41 - 48
• Main Authors: Lust, Andres, Lakio, Satu, Vintsevits, Julia, Kozlova, Jekaterina, Veski, Peep, Heinämäki, Jyrki, Kogermann, Karin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-11-2013
• Subjects: air; Anti-Inflammatory Agents, Non-Steroidal - chemistry; atomization; Calorimetry, Differential Scanning; coatings; differential scanning calorimetry; Drug Compounding - methods; Drug-layer coating; drugs; Hydrate formation; Hypromellose Derivatives; methylcellulose; Methylcellulose - analogs & derivatives; Methylcellulose - chemistry; Pellet; pellets; Piroxicam; Piroxicam - chemistry; polymers; Powder Diffraction; Process induced transformation; Raman spectroscopy; scanning electron microscopy; Solubility; Spectrum Analysis, Raman; temperature; Water - chemistry; X-radiation; X-Ray Diffraction; Pellet; Piroxicam; Drug-layer coating; Raman spectroscopy; Hydrate formation; Process induced transformation
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2013.08.036

Anhydrous piroxicam form I and piroxicam monohydrate were stable during an aqueous drug layer coating of pellets but a solid state transformation of amorphous piroxicam to piroxicam monohydrate occurred.
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 10min 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.