Bead layering as a process to stabilize nanosuspensions: influence of drug hydrophobicity on nanocrystal reagglomeration following in-vitro release from sugar beads

• Published in: Journal of pharmacy and pharmacology 2011-11, Vol.63 (11), p.1446-1453
• Main Authors: Kayaert, Pieterjan, Anné, Michaël, Van den Mooter, Guy
• Format: Article
• Language: English
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - chemistry; bead layering; Calcium Channel Blockers - chemistry; cinnarizine; Cinnarizine - chemistry; coating; Desiccation - methods; Drug Stability; Hydrophobic and Hydrophilic Interactions; Models, Theoretical; Nanoparticles - chemistry; nanosuspension; naproxen; Naproxen - administration & dosage; Naproxen - chemistry; Particle Size; Pharmaceutical Preparations - chemistry; Surface Properties; Suspensions - chemistry
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1111/j.2042-7158.2011.01351.x

Objectives  In this article the feasibility of fluidized bed bead coating of nanosuspensions of drugs with significantly different physicochemical properties was investigated as a process to transform nanosuspensions into a solid dosage form. The second aim was to see how those physicochemical properties affect the coating process and the subsequent in‐vitro dissolution process. Methods  Naproxen and cinnarizine were used as model drugs. A fluidized bed pellet coater with Würster insert was used to coat the nanosuspensions prepared by media milling on sugar beads. Key findings  Bead layering of cinnarizine nanosuspensions resulted in a complete dissolution in 15 min, compared to only 11% in 1 h for the unmilled powder. Naproxen also dissolved three times faster when formulated on a bead. A difference could be observed between naproxen and cinnarizine. Cinnarizine nanocrystals reagglomerate when released from the coating, resulting in a slower release when compared to the original nanosuspension. No agglomeration and no delay could be observed for naproxen. These differences are most likely caused by the difference of surface hydrophobicity between naproxen and cinnarizine. Conclusion  This study confirms that bead layering is a valuable drying technique that could complement spray drying and freeze drying, but more important is that we prove that drug physicochemical properties have a significant influence on in‐vitro dissolution performance after bead layering and this is not readily predictable from the information obtained from the original nanosuspension itself.