Merck

Effects of powder flow properties on capsule filling weight uniformity.

Drug development and industrial pharmacy (2013-08-02)
Juan G Osorio, Fernando J Muzzio
ABSTRACT

Filling capsules with the right amount of powder ingredients is an important quality parameter. The purpose of this study was to develop effective laboratory methods for characterizing flow properties of pharmaceutical powder blends and correlating such properties to weight variability in filled capsules. The methods used for powder flow characterization were bulk and tapped density, gravitational displacement rheometer (GDR) flow index, Freeman Technology V.4 (FT4) powder rheometer compressibility, FT4 basic flow energy (BFE), and cohesion parameters [cohesion, (C) and flow factor (ffc)] measured in a shear cell also using the FT4. Capsules were filled using an MG2-G140 continuous nozzle dosator capsule-filling machine. Powder flow properties were the most predominant factors affecting the weight and weight variability in the filled capsules. Results showed that the weight variability decreased with increasing bulk and tapped density, ffc and BFE, while the weight variability increased with increasing compressibility, cohesion and GDR flow index. Powder flow properties of the final blends were significantly correlated to the final capsule weight and weight variability of the filled capsules.

MATERIALS
Product Number
Brand
Product Description

Supelco
Florisil®, 100-200 mesh, fine powder
Supelco
Lactose, Anhydrous, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Florisil®, PR grade, 60-100 mesh, coarse powder
Sigma-Aldrich
Stearic acid, Grade I, ≥98.5% (capillary GC)
Supelco
Florisil®, for the determination of hydrocarbon acc. to ISO 9377-2
Supelco
Stearic acid, analytical standard
Sigma-Aldrich
Lactose, tested according to Ph. Eur.
Supelco
Florisil® PR, PR grade (analysis acc. to FDA)
Sigma-Aldrich
Stearic acid, ≥95%, FCC, FG
Supelco
Florisil®, <200 mesh, fine powder
Sigma-Aldrich
Stearic acid, reagent grade, 95%
Supelco
Melting Point Standard 69-71°C, analytical standard
Supelco
Stearic Acid, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Stearic acid, certified reference material, TraceCERT®
Stearic acid, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Stearic acid, Vetec, reagent grade, 94%
Sigma-Aldrich
Florisil®, 100-200 mesh
Lactose (anhydrous), European Pharmacopoeia (EP) Reference Standard
Supelco
Florisil® Adsorbent for Chromatography, 60-100 mesh
Supelco
Florisil® Adsorbent for Chromatography, 30-60 mesh