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High-Molecular-Weight Hypromellose from Three Different Suppliers: Effects of Compression Speed, Tableting Equipment, and Moisture on the Compaction

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Use of higher tableting speeds is gaining increasing importance for pharmaceutical industry. There is a profound lack of new studies of mechanical properties of hypromellose, and none of them evaluate different suppliers. Thus, the objective of this study was to investigate flow and compaction properties of different grades of hypromellose (type 2208) from three different suppliers, with particular focus on the effect of the compression speed. The flow properties were determined using flow time, shear cell, Carr index, and constant B from initial part of Heckel profile. Compaction properties were quantified using “out-of-die” Heckel, Walker, and Kuentz-Leuenberger models; two tensile strength profiles (tabletability and compactibility); and elastic recovery. Compaction was performed by both an instrumented single-punch press and a high-speed rotary press simulator. Due to larger, rounder, and smoother particles, both Methocel™ DC grades together with Benecel™ K4M showed better flow properties compared with other materials, with Metolose® K100M having the worst flow. Overall, Benecel™ K100M and Metolose® K100M showed the best compaction properties, closely followed by Metolose® K4M. Heckel analysis showed the highest compressibility of Benecel™ K100M, followed by both Methocel™ DC grades. Kuentz-Leuenberger model showed to have no practical superiority in comparison with Heckel model in the compression pressure range used. Results of strain rate sensitivity showed that Methocel™ K4M DC was the least susceptible to change of tableting speed, followed by Methocel™ K100M DC and both grades of Benecel™, and in contrast, both grades of Metolose® were the most sensitive. Effect of moisture on compaction was also studied.

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The authors wish to express sincere gratitude to KRKA, d.d., Novo mesto and Faculty of Pharmacy, University of Ljubljana, for providing us the opportunity and resources to develop and complete this work. The authors would like to thank Prof. Odon Planinšek from the Faculty of Pharmacy, University of Ljubljana, for his assistance in conducting the SEM analysis.


The research was supported by Krka, d.d., Novo mesto.

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Correspondence to Ilija German Ilić.

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Grdešič, P., Paudel, A. & German Ilić, I. High-Molecular-Weight Hypromellose from Three Different Suppliers: Effects of Compression Speed, Tableting Equipment, and Moisture on the Compaction. AAPS PharmSciTech 21, 203 (2020).

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