Application of Dominance-Based Rough Set Approach for Optimization of Pellets Tableting Process

Abstract

Multiple-unit pellet systems (MUPS) offer many advantages over conventional solid dosage forms both for the manufacturers and patients. Coated pellets can be efficiently compressed into MUPS in classic tableting process and enable controlled release of active pharmaceutical ingredient (APIs). For patients MUPS are divisible without affecting drug release and convenient to swallow. However, maintaining API release profile during the compression process can be a challenge. The aim of this work was to explore and discover relationships between data describing: composition, properties, process parameters (condition attributes) and quality (decision attribute, expressed as similarity factor f2) of MUPS containing pellets with verapamil hydrochloride as API, by applying a dominance-based rough ret approach (DRSA) mathematical data mining technique. DRSA generated decision rules representing cause–effect relationships between condition attributes and decision attribute. Similar API release profiles from pellets before and after tableting can be ensured by proper polymer coating (Eudragit® NE, absence of ethyl cellulose), compression force higher than 6 kN, microcrystalline cellulose (Avicel® 102) as excipient and tablet hardness ≥42.4 N. DRSA can be useful for analysis of complex technological data. Decision rules with high values of confirmation measures can help technologist in optimal formulation development.

Keywords

• tablets
• multiple-unit pellet system
• pharmaceutical technology
• DRSA
• data mining
• knowledge discovery