Quantification of Swelling and Erosion in the Controlled Release of a Poorly Water-Soluble Drug Using Synchrotron X-ray Computed Microtomography

• Published in: The AAPS journal Vol. 15; no. 4; pp. 1025 - 1034
• Main Authors: Yin, Xianzhen, Li, Haiyan, Guo, Zhen, Wu, Li, Chen, Fangwei, de Matas, Marcel, Shao, Qun, Xiao, Tiqiao, York, Peter, He, You, Zhang, Jiwen
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01-10-2013
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Chemistry, Pharmaceutical - methods; Delayed-Action Preparations - analysis; Delayed-Action Preparations - chemistry; Felodipine - analysis; Felodipine - chemistry; Pharmacology/Toxicology; Pharmacy; Research Article; Solubility; Synchrotrons; Tablets; Water - chemistry; X-Ray Microtomography - methods; statistical modeling; swelling and erosion; synchrotron radiation X-ray computed microtomography; drug release kinetics; gel-forming matrix tablet
• ISSN: 1550-7416; 1550-7416
• DOI: 10.1208/s12248-013-9498-y

The hydration layer plays a key role in the controlled drug release of gel-forming matrix tablets. For poorly water-soluble drugs, matrix erosion is considered as the rate limiting step for drug release. However, few investigations have reported on the quantification of the relative importance of swelling and erosion in the release of poorly soluble drugs, and three-dimensional (3D) structures of the hydration layer are poorly understood. Here, we employed synchrotron radiation X-ray computed microtomography with 9-μm resolution to investigate the hydration dynamics and to quantify the relative importance of swelling and erosion on felodipine release by a statistical model. The 3D structures of the hydration layer were revealed by the reconstructed 3D rendering of tablets. Twenty-three structural parameters related to the volume, the surface area (SA), and the specific surface area (SSA) for the hydration layer and the tablet core were calculated. Three dominating parameters, including SA and SSA of the hydration layer (
SA
hydration layer
and
SSA
hydration layer
) and SA of the glassy core (
SA
glassy core
), were identified to establish the statistical model. The significance order of independent variables was
SA
hydration layer
>
SSA
hydration layer
>
SA
glassy core
, which quantitatively indicated that the release of felodipine was dominated by a combination of erosion and swelling. The 3D reconstruction and structural parameter calculation methods in our study, which are not available from conventional methods, are efficient tools to quantify the relative importance of swelling and erosion in the controlled release of poorly soluble drugs from a structural point of view.