title: Sustained-release pellets of nifedipine using microcrystals combined with MCC-based matrix.
abstract: The purpose of this study was to prepare sustained-release pellets of nifedipine (NSPs) based on MCC matrix. Wet-milling and extrusion-spheronization techniques were employed to prepare the microcrystals and pellets, respectively. The drug release mechanism and the influencing factors were investigated. After milled with HPMC (E5), the mean particle size of nifedipine in co-grinding mixture (CGM) was 5 μm, which is 15-fold smaller than that of raw material. DSC, X-ray powder diffraction and microscopic observation confirmed the microcrystals of drug were maintained in the CGM. With increased milling time and the content of HPMC, the dissolution rate was greatly enhanced compared with the raw material. The NSPs prepared by MCC and the CGM, which was obtained by cogrinding nifedipine with 5% HPMC solution for 210 min, exhibited sustained release pattern within 8 h. Nifedipine release from MCC-based NSPs followed the Korsmeyer model and closely related to the microstructure of pellet. High stability of NSPs was confirmed after 6 months of accelerated stability test. Using commercially available sustained product as reference, bioequivalence study in beagle dogs was executed and two formulations were bioequivalent. This sustained release pellet formulation of nifedipine was advantageous with convenient and easy scaled-up preparation process.
authors: Department of Pharmaceutics, Shenyang Pharmaceutical University , Shenyang , People's Republic of China.
authors: Jinlong
authors: J
authors: Ma
authors: Juan
authors: J
authors: Wang
authors: Zhibo
authors: Z
authors: Cheng
authors: Tian
authors: T
authors: Yin
authors: Huan
authors: H
authors: Teng
authors: Hui
authors: H
authors: Xu
authors: Xing
authors: X
authors: Tang
authors: Cuifang
authors: C
authors: Cai
mesh_terms: D000818:Animals; D001682:Biological Availability; D002482:Cellulose / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000737:chemistry; D004285:Dogs; D004355:Drug Stability; D008855:Microscopy, Electron, Scanning; D009543:Nifedipine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010316:Particle Size; D012995:Solubility; D013810:Therapeutic Equivalency; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D003692:Delayed-Action Preparations; D014665:Vasodilator Agents; D002482:Cellulose; D009543:Nifedipine; C109691:microcrystalline cellulose
keywords: MCC-based matrix; nifedipine; release mechanism; sustained-release pellets; wet milling