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Investigation of Solid Phase Composition on Tablet Surfaces by Grazing Incidence X-ray Diffraction

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ABSTRACT

Purpose

To investigate solid state transformations of drug substances during compaction using grazing incidence X-ray diffraction (GIXD).

Methods

The solid forms of three model drugs–theophylline (TP), nitrofurantoin (NF) and amlodipine besylate (AMB)–were compacted at different pressures (from 100 to 1000 MPa); prepared tablets were measured using GIXD. After the initial measurements of freshly compacted tablets, tablets were subjected to suitable recrystallization treatment, and analogous measurements were performed.

Results

Solid forms of TP, NF and AMB showed partial amorphization as well as crystal disordering during compaction; the extent of these effects generally increased as a function of pressure. The changes were most pronounced at the outer surface region. The different solid forms showed difference in the formation of amorphicity/crystal disordering. Dehydration due to compaction was observed for the TP monohydrate, whereas hydrates of NF and AMB were stable towards dehydration.

Conclusions

With GIXD measurements, it was possible to probe the solid form composition at the different depths of the tablet surfaces and to obtain depth-dependent information on the compaction-induced amorphization, crystal disordering and dehydration.

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ACKNOWLEDGMENTS & DISCLOSURES

Vishal Koradia is thankful to the Drug Research Academy (Copenhagen, Denmark) and H. Lundbeck A/S (Copenhagen, Denmark) for financial support. Matrix Laboratories Limited is thanked for providing amlodipine besylate sample.

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Author notes

  1. Vishal Koradia

    Present address: Technical R&D, Novartis Pharma AG, 4056, Basel, Switzerland

Authors and Affiliations

  1. Department of Pharmaceutics and Analytical Chemistry Faculty of Pharmaceutical Sciences, University of Copenhagen, 2100, Copenhagen, Denmark

    Vishal Koradia, Jørn Møller-Sonnergaard & Jukka Rantanen

  2. Department of Physics and Astronomy, University of Turku, 20014, Turku, Finland

    Mikko Tenho, Jarno Salonen & Vesa-Pekka Lehto

  3. Preformulation, H. Lundbeck A/S, 2500, Valby, Denmark

    Heidi Lopez de Diego

  4. Pharmaceutical Development, H. Lundbeck A/S, 2500, Valby, Denmark

    Michiel Ringkjøbing-Elema

  5. Department of Applied Physics, University of Eastern Finland, POB 1627, 70211, Kuopio, Finland

    Vesa-Pekka Lehto

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  1. Vishal Koradia
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Correspondence to Jukka Rantanen.

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Koradia, V., Tenho, M., Lopez de Diego, H. et al. Investigation of Solid Phase Composition on Tablet Surfaces by Grazing Incidence X-ray Diffraction. Pharm Res 29, 134–144 (2012). https://doi.org/10.1007/s11095-011-0520-8

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  • DOI: https://doi.org/10.1007/s11095-011-0520-8

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