Characterization and selection of suitable grades of lactose as functional fillers for capsule filling: part 1

Abstract

The purpose of this work is to characterize thermal, physical and mechanical properties of different grades of lactose and better understand the relationships between these properties and capsule filling performance. Eight grades of commercially available lactose were evaluated: Pharmatose 110 M, 125 M, 150 M, 200 M, 350 M (α-lactose monohydrate), AL (anhydrous lactose containing ∼80% β-AL), DCL11 (spray dried α-lactose monohydrate containing ∼15% amorphous lactose) and DCL15 (granulated α-lactose monohydrate containing ∼12% β-AL). In this study, different lactose grades were characterized by thermal, solid state, physical and mechanical properties and later evaluated using principal component analysis (PCA) to assess the inter-relationships among some of these properties. The lactose grades were characterized by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XRD), moisture sorption/desorption isotherms, particle size distribution; the flow was characterized by Carr Index (CI), critical orifice diameter (COD) and angle of friction. Plug mechanical strength was estimated from its diametric crushing strength. The first and second principal components (PC) captured 47.6% and 27.4% of variation in the physical and mechanical property data, respectively. The PCA plot grouped together 110 M, AL, DCL11 and DCL15 on the one side of plot which possessed superior properties for capsule formulation and these grades were selected for future formulation development studies (part II of this work).

• α-Lactose monohydrate
• β-anhydrous lactose
• capsule filling
• filler characterization
• plug mechanical strength

Acknowledgements

Author will like to acknowledge Division of Product Quality and Research, CDER, FDA (Silver Spring, MD), for the use of their instruments.

Declaration of interest

The views and opinions expressed in this paper are only of the authors, and do not necessarily reflect the views or policies of the FDA. Authors thank the financial support of this research provided by DMV-Fonterra Excipients (Goch, Germany). This work was also supported by University of Maryland Department of Pharmaceutical Sciences predoctoral Dr. Frank J. Slama and H. A. B. Dunning fellowship.