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Int J Pharm. 2020 Jan 5;573:118827. doi: 10.1016/j.ijpharm.2019.118827. Epub 2019 Nov 19.

Study of drug particle distributions within mini-tablets using synchrotron X-ray microtomography and superpixel image clustering.

Author information

1
Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Switzerland. Electronic address: leonie.hattler@gmail.com.
2
Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Switzerland. Electronic address: gabriela.quebatte@unibas.ch.
3
Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland. Electronic address: jennifer.keiser@swisstph.ch.
4
Omya International AG, Oftringen, Switzerland. Electronic address: joachim.schoelkopf@omya.com.
5
Swiss Light Source, Paul Scherrer Institute, Villigen-PSI, Switzerland. Electronic address: Christian.Schlepuetz@psi.ch.
6
Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Switzerland. Electronic address: joerg.huwyler@unibas.ch.
7
Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Switzerland. Electronic address: maxim.puchkov@unibas.ch.

Abstract

Uniform drug distribution within fast disintegrating tablets is a key quality measure to ensure a reliable, steady, and targeted release of the contained active pharmaceutical ingredients. In this work, the drug particle distribution in mini-tablets was studied with synchrotron phase contrast X-ray microtomography. Mini-tablets had a weight of 9.5 mg and a drug load from 2.5% to 20%. Moxidectin, a drug used for treatment of parasitic infections, was used as a model compound. Drug content covered a range from 91% to 121% of the target dose. A linear iterative clustering (SLIC) superpixel method was used for segmentation, analysis, and visualization of the spatial distribution of individual tablet components (i.e., pores, excipients, and drug). Results show that the drug was not uniformly distributed within the tablet, revealing an increasing drug load towards the tablets' outer boundaries and thus indicative of a radial displacement of drug particles during compaction. The presented method can be used for the quantitative analysis of drug content and drug distribution within pharmaceutical tablets, allowing for the optimization of fast disintegrating formulations. The results also affirm that that drug loads up to 20% will not lead to segregation for moxidectin.

KEYWORDS:

Distribution analysis; Functionalized calcium carbonate; Mini-tablets; Moxidectin; Percolation theory; Superpixel clustering; Synchrotron X-ray microtomography

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