title: Development and comparison of intramuscularly long-acting paliperidone palmitate nanosuspensions with different particle size.
abstract: The main purpose of this study was to develop and compare the pharmacokinetic behavior of two paliperidone palmitate (PP) nanosuspensions with different particle size after intramuscular (i.m.) administration. PP nanosuspensions were prepared by wet media milling method and the mean particle size of nanosuspension was controlled as 1,041 ± 6 nm (A) and 505 ± 9 nm (B), respectively. The morphology of nanosuspensions was observed by scanning electron microscope (SEM). Differential scanning calorimeter (DSC) and powder X-ray diffraction (PXRD) confirmed the crystallinity of PP in nanosuspensions. The physical and chemical stabilities of nanosuspensions A and B were investigated by particle analyzer and HPLC after storage for 2 months at 25°C, 4°C and mechanical shaking condition. No obvious change in particle size and chemical degradation of drug were observed. Following single-dose i.m. administration to beagle dogs, the release of paliperidone lasted for nearly 1 month. The Tmax of nanosuspensions A and B was 6 (d) and 10 (d). The AUC0-t and Cmax of nanosuspensions A was 2.0-fold and 1.8-fold higher than nanosuspensions B (p<0.05). The results demonstrated that PP nanosuspensions formulation had long-acting effect. Nanosuspension A with a larger particle size performed better than nanosuspension B. As a result, it is important to design appropriate particle size of nanosuspensions for i.m. administration in order to produce larger therapeutic effect.
authors.affiliation: Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, China.
authors.forename: Donglei
authors.initials: D
authors.lastname: Leng
authors.affiliation: Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, China.
authors.forename: Hongming
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, China.
authors.forename: Guangjing
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, China.
authors.forename: Mengran
authors.initials: M
authors.lastname: Guo
authors.affiliation: Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, China.
authors.forename: Zhaolu
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Physical Chemistry, School of Pharmacy, Shenyang Pharmaceutical University, China. Electronic address: xulu1974@hotmail.com.
authors.forename: Lu
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, China. Electronic address: wangyongjun@syphu.edu.cn.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D002152:Calorimetry, Differential Scanning; D003692:Delayed-Action Preparations; D004285:Dogs; D007273:Injections, Intramuscular; D007555:Isoxazoles / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000648:ultrastructure; D000068882:Paliperidone Palmitate; D010168:Palmitates / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D010316:Particle Size; D012995:Solubility; D013535:Suspensions; D014961:X-Ray Diffraction
chemical_list: D003692:Delayed-Action Preparations; D007555:Isoxazoles; D010168:Palmitates; D013535:Suspensions; D000068882:Paliperidone Palmitate
keywords: Nanosuspensions; Paliperidone palmitate; Particle size; Pharmacokinetics