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Safety and Robustness of Coated Pellets: Self-Healing Film Properties and Storage Stability

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Abstract

Purpose

Aim of the study was to verify the safety of chlorpheniramine maleate pellets, coated with blends of poly(vinyl acetate) and poly(vinyl alcohol)–poly(ethylene glycol) graft copolymer. Therefore, the impact of mechanical forces and storage conditions on the drug release was investigated.

Results

Similar release profiles before and after compression of the pellets to tablets underlined the high film robustness. A damage of the film coat with a razor blade resulted in a premature release, but without a burst. After a similar damage with a needle, the release profile remained almost unchanged, which indicated a swelling based self repair mechanism of the film. Additional studies were dedicated to the storage stability at three different conditions. A slightly delayed release was obtained after 6 months storage at 25°C and a marginally accelerated release was measured after storage at elevated temperatures. No drug migration into the coating layer was detected during storage by confocal Raman microscopy. 1H-NMR analysis during storage demonstrated, that no polymer or drug degradation had occurred and the plasticizer concentration remained constant.

Conclusion

The polyvinyl based coating blend for modified release pellets demonstrated a high safety, due to their high robustness and compressibility as well as their satisfying storage stability.

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ACKNOWLEDGMENTS

The author likes to thank J. France and L. Lesinski for their support on NMR and Confocal Raman measurements as well as J. Baer and D. Rietsch for arranging the long-term stability study. Finally, the support of BASF on the film coating polymers is acknowledged.

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Authors and Affiliations

  1. Technical Research & Development, Novartis Pharma AG, 4056, Basel, Switzerland

    Simon Ensslin, Klaus Peter Moll & Thomas Haefele-Racin

  2. Institute of Pharmacy, Martin Luther University, Wolfgang-Langenbeck-Str. 4, 06120, Halle, Germany

    Simon Ensslin & Karsten Mäder

Authors
  1. Simon Ensslin
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  2. Klaus Peter Moll
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  3. Thomas Haefele-Racin
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  4. Karsten Mäder
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Corresponding author

Correspondence to Karsten Mäder.

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Supplementary information

Normalized Raman signal intensity plotted versus the transversal cross section of the overlay picture (coated CPM pellets, sample IV, after 6 months storage at 40 °C / 75 % rH).(GIF 66.6 KB)

High resolution image file (TIFF 87.8 MB).

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Ensslin, S., Moll, K.P., Haefele-Racin, T. et al. Safety and Robustness of Coated Pellets: Self-Healing Film Properties and Storage Stability. Pharm Res 26, 1534–1543 (2009). https://doi.org/10.1007/s11095-009-9866-6

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  • DOI: https://doi.org/10.1007/s11095-009-9866-6

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