A Case Study Effect of Binder Type on Dry Granulation and Tablet Compression Properties of a Model Formulation
Anshul Gupte¹, Michael Dehart¹, Rahul Haware²
¹Metrics Contract Services, 1240 Sugg Parkway, Greenville, NC, 27834
²Campbell University College of Pharmacy & Health Science, Buies Creek, NC, 27506
The purpose of the present investigation was to compare the impact of roller compaction processing parameters and resulting tableting properties of roller compacted granules of Avicel ® DG (ADG) [Spray Dried-Co-processed Microcrystalline Cellulose], physical mixture of Avicel ® 101 (75%) and Anhydrous Di-calcium Phosphate) (25%)] (PADCP), and Co-Povidone [Kollidon ® VA-64 Fine] (KVA64).
The commonly used binders in dry granulation include Avicel ®(microcrystalline cellulose), Mannitol, Lactose, Starch, Hypromellose, Hydroxypropyl cellulose, and others¹. The choice of binders available for dry granulation depends on number of factors specifically, API particle size, binder particle size, % of API in the formulation, tablet strength desired, disintegration time desired, reduced passes on the RC, and % of Fines¹,². Additionally, recently the use of one-step co-processed binders such as Avicel® DG, Kollidon ®, Starch 1500 ® is gaining advantage².
The binders in this study were selected as they represented binders with differences in plasticity, particle size, and the amount required to produce tablets with desired tablet strength.
Gerteis Roller Compactor used in this study offers significant improved capabilities to the dry granulation process by providing qualified gap and force measurements, fully instrumented, constant ribbon density, easy scale up to production, perfect gap seal system, and process data acquisition³.
A model intra-granular formulation consisting of API: Acetaminophen (30%w/w), Disintegrant: Crospovidone (3% w/w), Binder (64%w/w), and Lubricant: Magnesium stearate (0.5%w/w) was prepared. Three processing parameters: ribbon thickness (mm) [RT: 2, 3, 4], roller force (kN/cm) [RF: 6, 12, 18], roller speed (RPM) [RS: 2, 4, 8, 12] were studied low, target, and high levels using mixed experimental design. Constant mill ribbon speed (90 rpm) and mill screen size (0.8 mm) was used. Roller compaction and milling were executed using Gerteis Mini-Pactor Roller Compactor. Final blend of milled granules were prepared by adding additional 2% Crospovidone and 0.5% magnesium stearate. Tablets from each of the runs below were compressed using 0.2756 × 0.6063 mm capsule shaped tooling at 500 mg target tablet weight with an instrumented tablet press at the same compression force to study the effects of the roller compacted granules on the tablet properties.
Roller compacted granules properties [granules to fine ratio (GFR) and Carr’s index (CI)], and tableting properties [tablet thickness (TT), tablet breaking force (TBF), and disintegration time (DT)] were investigated. Design variables and their interactions and square effects correlations with roller compacted granules and tableting properties were quantified by multivariate methods.
1. Comparison of different dry binders for roll compaction/dry granulation. Herting MG, Klose K, Kleinebudde P. Pharm Dev Technol. 2007;12(5):525-32
2. Excipients & Actives for Pharma | No. 20, May 2008