title: In situ nondestructive sediment characterization and resuspendability evaluation of concentrated aqueous paliperidone palmitate suspensions in prefilled syringes by low-field one-dimensional pulsed-field gradient NMR profilometry.
abstract: This work aims to demonstrate the usefulness of a low-field one-dimensional pulsed-field gradient NMR (1D pfg NMR) profilometry technique to enable in situ nondestructive sediment characterization and resuspendability quantification of concentrated prefilled injectable suspensions. Aqueous paliperidone palmitate suspensions were used as model samples and low-intensity centrifugation was evaluated as a long-term gravity simulation approach. The low-field 1D pfg NMR technique allowed a detection zone of 2.5 cm in height for water content measurement of syringe samples using a Teflon syringe holder. Thus, the sediment compactness could be deduced from its water content. Quantitative evaluation of resuspendability was realized by front tracking of the NMR profile signals, which yielded the exponential sediment volume decay constant as a resuspendability quantification parameter. The study shows that both active ingredient particle size distribution and storage temperature had significant effects on the sedimentation rate and the resuspendability of the suspensions. The centrifugation method proved to be useful as a long-term gravity simulation and screening method, although the results should be interpreted with caution due to its higher acceleration and compression force imposed on the active ingredient particles.
authors.affiliation: Particle and Interfacial Technology Group, Ghent University, Gent, Belgium.
authors.forename: Wuxin
authors.initials: W
authors.lastname: Zhu
authors.forename: Lien
authors.initials: L
authors.lastname: Vermeir
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Govoreanu
authors.forename: Katrien
authors.initials: K
authors.lastname: Verbruggen
authors.forename: Tina
authors.initials: T
authors.lastname: Ariën
authors.forename: Arne
authors.initials: A
authors.lastname: Verliefde
authors.forename: Paul
authors.initials: P
authors.lastname: Van der Meeren
mesh_terms: D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000737:chemistry*; D002498:Centrifugation / Q000379:methods; D004356:Drug Storage; D006112:Gravitation; D007555:Isoxazoles / Q000008:administration & dosage / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D000068882:Paliperidone Palmitate; D010168:Palmitates / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D013535:Suspensions; D013594:Syringes; D013696:Temperature; D014867:Water / Q000737:chemistry
chemical_list: D014150:Antipsychotic Agents; D007555:Isoxazoles; D010168:Palmitates; D013535:Suspensions; D014867:Water; D000068882:Paliperidone Palmitate