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Synchrotron 3D method elucidates the controlled release mechanism of poorly soluble drugs
Update time: 2013-07-24
Author: 张继稳组
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Gel matrix tablets are the primary type of oral controlled release drug delivery systems widely used, particularly those containing hydroxypropyl methylcellulose (HPMC). The drug release kinetics is controlled by the hydration dynamics of the gel layer, including the swelling and erosion of the matrix. The relative importance of swelling and erosion in the controlled release varies in line with the solubility of the drugs. Some empirical mathematical models have been established for the gel matrix tablets governing the transport of solutes, while the dynamic changes to the internal structure during the hydration of the tablet are unclear.

A joint team directed by Professor ZHANG Jiwen from Shanghai Institute of Materia Medica (SIMM), Professor XIAO Tiqiao from Shanghai Institute of Applied Physics (SINAP) in Chinese Academy of Sciences and Professor Peter York from University of Bradford (UoB) have set focus to the topic using the synchrotron radiation X-ray computed microtomography (SR-μCT). Mr. YIN Xianzhen, Dr. LI Haiyan and Dr. HE You investigated the hydration dynamics and quantified the relative importance of swelling and erosion on felodipine release from the HPMC matrix tablets.

Based on SR-μCT with 9-micron resolution, the surface morphology, the internal 3D structure of the tablets and the hydration layer dynamic characteristics were clearly visualized from the 2D monochrome X-ray CT images and the reconstructed 3D tomographic images. Based on the three-dimensional reconstruction, 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, namely, SA and SSA of the hydration layer (SAhydration layer and SSAhydration layer) and SA of the glassy core (SAglassy core), were identified to establish the statistical model and then to quantify the relative importance of swelling and erosion on felodipine release. The significance order of independent variables was SAhydration layer > SSAhydration layer > SAglassy core, which quantitatively indicated that the release of felodipine was dominated by a combination of erosion and swelling.

The new methodology has great potential to elucidate the controlled release mechanism of poorly soluble drugs from a structural point of view, which provides theoretical basis for the design of gel matrix controlled release drug delivery systems.

This work has been published online by American Association of Pharmaceutical Scientists Journal (AAPS J) on July 16, 2013 .

Full Text: http://link.springer.com/article/10.1208/s12248-013-9498-y

Figures: Quantification of the 3D hydration dynamics and the relative importance of swelling and erosion in the controlled release of felodipine from HPMC tablets(Image by SIMM)

 
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