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Roller Compaction of Hydrophilic Extended Release Tablets—Combined Effects of Processing Variables and Drug/Matrix Former Particle Size

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Abstract

The present study shows that roller compaction (RC) can successfully be used as a granulation method to prepare hydroxypropyl methylcellulose (HPMC)-based extended release matrix tablets containing a high drug load, both for materials deforming mainly by fragmentation (paracetamol) as for those having mainly plastic deformation (ibuprofen). The combined effect of RC process variables and composition on the manufacturability of HPMC tablets was investigated. Standard wet granulation grade HPMC was compared with a larger particle size direct compressible HPMC grade. Higher roll pressure was found to result in larger paracetamol granules and narrower granule particle size distributions, especially for formulations containing smaller size HPMC. However, for ibuprofen, no clear effect of roll pressure was observed. High roll pressure also resulted in denser ribbon and less bypass fines during RC. Loss of compactibility was observed for granules compared to powder blends, which was found to be related to differences in granule porosity and morphology. Using the large-sized HPMC grade did in some cases result in lower tensile strength tablets but had the advantage to improve the powder flow into the roller compactor. This work also indicates that when the HPMC level lies near the percolation threshold, significant changes can occur in the drug release rate due to changes in other factors (raw material characteristics and processing).

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ACKNOWLEDGMENTS

We acknowledge Lars Johnson (AZ) for his assistance with the permeability tests, Mervi Lindman (University of Helsinki) for taking SEM images of granules and Pirjo Tajarobi (AZ) for providing particle size data for paracetamol. HPMC DC Gen I was kindly supplied by Dow Pharma and Food Solutions.

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Authors and Affiliations

  1. Faculty of Pharmacy, Industrial Pharmacy, University of Helsinki, Helsinki, Finland

    Johanna Heiman & Anne Juppo

  2. Formulation Science, AstraZeneca R&D Mölndal, 431 83, Mölndal, Sweden

    Johanna Heiman, Farhad Tajarobi, Bindhumadhavan Gururajan & Susanna Abrahmsén-Alami

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  1. Johanna Heiman
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  2. Farhad Tajarobi
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  3. Bindhumadhavan Gururajan
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  4. Anne Juppo
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  5. Susanna Abrahmsén-Alami
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Correspondence to Susanna Abrahmsén-Alami.

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Heiman, J., Tajarobi, F., Gururajan, B. et al. Roller Compaction of Hydrophilic Extended Release Tablets—Combined Effects of Processing Variables and Drug/Matrix Former Particle Size. AAPS PharmSciTech 16, 267–277 (2015). https://doi.org/10.1208/s12249-014-0219-3

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