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34 January 2018 Tablets & Capsules eye on Edmont Stoyanov, Berna Ehlig, and Wade Tanev Nisso In this edition of the column, researchers from Nisso present the results of a study that examined how the molecular weight (MW) of different hydroxypropyl cellulose (HPC) grades affected the characteristics of granules and tablets prepared by two wet granulation methods: high shear and fluid bed. Wet granulation is one of the most commonly used methods of d e v e l o p i n g s o l i d d o s a g e d r u g products. Among the advantages of this classical granulation method over other technologies are a narrow particle size distribution (PSD) of the granules, few fine particles that yield little dust, more consistent powder flow, better control of granule size, very good binder homogeneity, and good powder compactability. The most important excipient group in a successful wet granulation formulation is the binder. Within this group are polymers with different chemistries, mechanical properties, and viscosity ranges. The polymer binder HPC has attracted the attention of formulators in the last decade due to its superior mechanical properties, chemical stability, and multi-functionality. This cellulosic ether appears to work even in challenging formulations with high- dose, poorly compressible drug products, where other binders usually fail. Low-viscosity (low-MW) HPC grades are used as a binder for all types of wet granulation including high- shear, fluid-bed, extrusion, and melt granulation. To select the suitable grade, scientists often must conduct many experiments, adjusting the d e s i r e d p o w d e r a n d t a b l e t characteristics. In this study, we focused on the influence of the HPC MW on the granule and tablet characteristics in fluid-bed and high- shear wet granulation. Materials and methods The study used HPCs with MWs of 40,000 daltons (Nisso HPC-SSL and SSL SFP from Nippon Soda, Tokyo, Japan), 100,000 daltons (Nisso HPC-SL and SL FP), and 140,000 daltons (Nisso HPC-L and L FP). Paracetamol (Atabay, Istanbul, Turkey) w a s u s e d a s a m o d e l a c t i v e pharmaceutical ingredient (API); use level was 85 percent by weight. Croscarmellose sodium (Vivasol, JRS Pharma, Patterson, NY) was used as a superdisintegrant and magnesium stearate (Lehmann & Voss, Hamburg, Germany) was used as a lubricant. A fluid-bed granulator (Solidlab 2, Bosch, Waiblingen, Germany) and high-shear granulator (Mycromix, Bosch) were used for the granulation of pure paracetamol. The PSD of the granules was analyzed by laser diffraction Table 2 Properties of HPC grades used as binder HPC grade Molecular weight Median particle size (m) 1 Average viscosity (mPa•s) 2 SSL 40,000 85 2.5 SSL SFP 40,000 20 2.5 SL 100,000 160 5.0 SL FP 100,000 95 5.0 L 140,000 160 8.0 1. By laser diffraction 2. At 20°C; 2% aqueous solution Ingredients Quantity (mg) Ratio (%) Paracetamol 510.00 85.00 Binder 60.00 10.00 Croscarmellose sodium 24.00 4.00 Magnesium stearate 6.00 1.00 Total 600.00 100.00 Table 1 Model formulation excipients Table 3 Process parameters of fluid-bed granulation HPC grade Inlet temperature Inlet conditioning Air flow Spray rate Spray pressure Micro-climate pressure SSL 80°C Dehumidifying (1.8 g/kg) 130-170 m 3 /h 70 g/min 0.6 bar 0.1 bar SL 80°C Dehumidifying (1.8 g/kg) 130-170 m 3 /h 70 g/min 0.6 bar 0.1 bar L 80°C Dehumidifying (1.8 g/kg) 130-170 m 3 /h 70 g/min 0.6 bar 0.1 bar (Qicpic, Sympatec, Clausthal- Zellerfeld, Germany). Tablets were compressed using a rotary tablet press with 16 stations (TPR200, Bosch).