title: Release behaviour of single pellets and internal fine 3D structural features co-define the in vitro drug release profile.
abstract: Multi-pellet formulations are advantageous for the controlled release of drugs over single-unit dosage forms. To understand the diffusion controlled drug release mechanism, the pellet structure and drug release from a single pellet (not at dose level) were studied using synchrotron radiation X-ray computed microtomography (SR-μCT) and a sensitive LC/MS/MS method. The purpose of this article is to introduce a powerful, non-invasive and quantitative technique for studying individual pellet microstructures and to investigate the relationship between the microstructure and drug release from single pellets. The data from the single pellet dissolution measurements demonstrated that the release profile of capsules containing approximately 1,000 pellets per unit dose was the summation of the release profiles of the individual pellets. The release profiles of single tamsulosin hydrochloride (TSH) pellets formed three groups when a cluster analysis was performed, and the dissolution rate of the individual pellets correlated well with the combined effects of the drug loading, volume and surface area of the pellets (R(2) = 0.9429). In addition, the void microstructures within the pellet were critical during drug release. Therefore, SR-μCT is a powerful tool for quantitatively elucidating the three-dimensional microstructure of the individual pellets; because the microstructure controls drug release, it is an important parameter in the quality control of multi-pellet formulations.
authors.affiliation: Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 201203, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Yang
authors.forename: Xianzhen
authors.initials: X
authors.lastname: Yin
authors.forename: Caifen
authors.initials: C
authors.lastname: Wang
authors.forename: Haiyan
authors.initials: H
authors.lastname: Li
authors.forename: You
authors.initials: Y
authors.lastname: He
authors.forename: Tiqiao
authors.initials: T
authors.lastname: Xiao
authors.forename: Lixin
authors.initials: L
authors.lastname: Sun
authors.forename: Jiasheng
authors.initials: J
authors.lastname: Li
authors.forename: Peter
authors.initials: P
authors.lastname: York
authors.forename: Jun
authors.initials: J
authors.lastname: He
authors.forename: Jiwen
authors.initials: J
authors.lastname: Zhang
mesh_terms: D002214:Capsules / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D002853:Chromatography, Liquid; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D007700:Kinetics; D013058:Mass Spectrometry; D012995:Solubility; D017356:Synchrotrons; D055114:X-Ray Microtomography
chemical_list: D002214:Capsules