Issue link: https://www.e-digitaleditions.com/i/922724
Tablets & Capsules January 2018 35 HPC-SL FP, and HPC-L FP were used in the high-shear granulation. They were added dry, with purified water serving as the granulation liquid. Results and discussion: Fluid-bed granulation Each HPC aqueous solution was prepared to the same 8 percent concentration. The average viscosity of the different solutions, expressed in millipascal-seconds, was 20 mPa·s for the SSL, 65 mPa·s for the SL, and 200 mPa·s for the L. Table 3 lists the main process parameters for fluid-bed granulation. PSD of the granules. A strong effect of the HPC's MW on the granules' PSD was observed. The lowest MW grade (HPC-SSL) produced finer granules with a very narrow PSD (Figure 2). The coarsest granules, with a broader PSD, were observed to result from HPC-L, which had the highest MW of the tested grades. There was a clear relationship between the HPC's MW and the size of the granules: SSL < SL < L. This shows that changing the HPC grade makes it possible to modulate the granule particle size and PSD without changing the product's formulation or granulation parameters. Powder compactability. The granules obtained were formed into tablets at five different compression forces (Figure 3). The moisture content of all the powder blends was similar, thus its effect on the powder compaction properties can be excluded. At compression forces up to 15 kilonewtons (kN), the powders showed approximately the same compactability. At higher compression forces, the granules made with HPC- SSL demonstrated much better compaction properties and yielded the highest tablet breaking forces. A possible reason for the superior deformability of the SSL could relate to the mobility of the polymer chain in the dry powder. The short polymer chain of SSL (MW of 40,000) is more linear, allowing more deformation after compression. HPC grades SL and L have higher MWs (100,000 and 140,000) and are more sterically bound in dry form, creating a binder with more elasticity and less deformability. Figure 1 Granulation procedures Paracetamol Paracetamol and HPC Granulation Granulation Scale: 1,800 g Scale: 1,800 g Mixing Mixing Binder solution Purified water Fluidized bed HPC-SSL, SL, L as 8% aqueous solution Spraying rate: 70 g/min Inlet temperature: 80˚ C Air flow 130-170 m 3 /h 3 mm 3 mm Drying Drying Sieving Sieving 1. Croscarmellose sodium: 5 min 2. Magnesium stearate: 3 min 1. Croscarmellose sodium: 5 min 2. Magnesium stearate: 3 min Compression: 600 mg, 13-mm flat-faced tablets Compression: 600 mg, 13-mm flat-faced tablets a. Fluid-bed method b. High-shear method Table 4 Process parameters of high-shear granulation HPC grade Impeller speed (rpm) Chopper speed (rpm) Spray rate (mL) Spraying time (min) Wet massing time (min) SSL 50 1,500 76 5 2 SL 50 1,500 76 5 2 L 50 1,500 76 5 2 Table 5 Parameters of drying process HPC grade Process filter type Inlet air conditioning Inlet temperature Air flow SSL SFP Granulation Dehumidifying (4 g/kg) 69°C 160 m 3 /h SL FP Granulation Dehumidifying (4 g/kg) 60°C 160 m 3 /h L FP Granulation Dehumidifying (4 g/kg) 60°C 160 m 3 /h The model formulation included a h i g h d o s e o f p a r a c e t a m o l ( 8 5 percent) and 10 percent HPC, which served as the binder (Table 1). Six different grades of HPC were selected based on their MW and median particle size (Table 2). Grades of regular particle size HPC-SSL, SL, and L were used in the fluid-bed granulation and were added as an 8 percent aqueous solution. Grades of fine particle size HPC-SSL SFP,