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

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.