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Amorphization of Indomethacin by Co-Grinding with Neusilin US2: Amorphization Kinetics, Physical Stability and Mechanism

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Abstract

Purpose

To quantify the effects of the ratio of indomethacin to Neusilin US2 and the processing humidity on the amorphization kinetics, stability and nature of the interaction.

Materials and Methods

A porcelain jar mill with zirconia balls was used to affect conversion of the physical mixtures (48 g) of indomethacin and Neusilin US2 (in the ratios 1:1 to 1:5) to amorphous states at room temperature (25°C) employing either 0% RH or 75% RH. The percent crystallinity in the samples was determined from ATR-FTIR scans chemometrically. The physical stability of these co-ground amorphous powders was evaluated at 40°C/75% RH and 40°C/0% RH.

Results

The lower the ratio of indomethacin to Neusilin US2, the faster is the amorphization during co-grinding. Higher humidity facilitates amorphization with a more pronounced effect at the lower ratio of indomethacin to Neusilin US2. There is further amorphization of some of the partially amorphized samples on storage at 40°C/75% RH for 3 months. Hydrogen bonding and surface interaction between metal ions of Neusilin US2 and indomethacin can explain changes in the FTIR spectra.

Conclusions

The processing humidity and the ratio of indomethacin to Neusilin US2 are important factors to be considered to affect amorphization during ball milling. Amorphous indomethacin can be stabilized by co-grinding with Neusilin US2.

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Acknowledgments

The authors gratefully acknowledge financial support from the Dane O. Kildsig Center for Pharmaceutical Processing Research. We are thankful to Mr. Gary Lavigne and Dr. Jack Gromek at the Institute of Material Sciences, University of Connecticut for assistance with FTIR instrument and X-ray diffractometer, respectively. We also want to thank Mr. Sharad Murdande at Pfizer, Groton, CT for his help with HPLC analysis.

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Authors and Affiliations

  1. School of Pharmacy, University of Connecticut, Storrs, Connecticut, 06269, USA

    Deepak Bahl & Robin H. Bogner

  2. Institute of Material Science, University of Connecticut, Storrs, Connecticut, 06269, USA

    Robin H. Bogner

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  1. Deepak Bahl
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  2. Robin H. Bogner
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Correspondence to Robin H. Bogner.

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Bahl, D., Bogner, R.H. Amorphization of Indomethacin by Co-Grinding with Neusilin US2: Amorphization Kinetics, Physical Stability and Mechanism. Pharm Res 23, 2317–2325 (2006). https://doi.org/10.1007/s11095-006-9062-x

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  • DOI: https://doi.org/10.1007/s11095-006-9062-x

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