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.

Advances in Structure Pharmaceutics from Discovery to Evaluation and Design

“…(B) Correlation between the surface area and cumulative amount released at different times. Reproduced with permission from ref . Copyright 2014 American Association of Pharmaceutical Scientists.…”

Review on Starter Pellets: Inert and Functional Cores

“…In recent decades, with the development of technology and the introduction of new testing equipment and software, it has become possible to study the exact and complete 3D morphology of particles of the same size as pellets. Thus, for example, micro-CT (µCT) or synchrotron radiation X-ray computed microtomography (SR-µCT) can also be used to examine the sphericity of pellets [90,91]. The latter method is also applicable for the study of drug distribution of minitablets of the same size range as pellets [92].…”

Bridging the structure gap between pellets in artificial dissolution media and in gastro-intestinal tract in rats

“…For example, the drug release kinetics and quantification of swelling and erosion in the controlled release tablets were investigated. The mechanism of controlled drug release and pellet structure variation were correlated via a single pellet observation strategy 18 . An SR-μCT microstructural characterization combined with chemical determination approach for formulation development of material distribution in multiple-unit pellet system tablet was developed 19 .…”