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).

To investigate the influence of machine operating variables on formulations derived from lactose types in capsule filling: part 2

“…The presence of a higher fraction fine particles in AL compared to the other grades may contribute to higher fill weights. As reported in the first part of this study 33 , AL showed a skewed particle size distribution with higher % of finer particles. Thus, under tamping pressure, more fines could migrate or rearranged themselves into the intervoid spaces, thus, increasing the packing density.…”

“…In the part 1 of this study 33 , total eight grades of lactose were characterized for their thermal, solid-state, physical and mechanical properties. Results indicated that difference in the presence of anomer type, physical and mechanical properties like particle size and distribution, Carr index, Critical Orifice Diameter (COD), angle of friction and powder compaction govern the formation of qualitative hard intact plugs.…”

“…The size 1 tamping pins of this machine have been instrumented in the manner previously described 17,20,21,33 for HK dosing disc machines with 350 strain gages (Vishay Intertechnology, Malvern, PA) to measure the tamping and ejection forces (EF). The data acquisition procedure was fully digitalized.…”

“…In Part 1 of this study, eight different grades of lactose were characterized 33 . In summary, these lactose types differed based on the amount of alpha (a-) and beta (b-) anomers, the presence or absence of amorphous content, differences in particle size distribution and differences in particle shape.…”

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“…This finding was well-anticipated and pretty in-line with DSC studies of different grades of lactose reported in literature. [36] Graphical optimization of measured responses (overlay plot) Design Expert ® Ver.9.0.0.7 (Stat-Ease Inc., Minneapolis, MN 55413) has in-built option for graphical optimization which frames "design-space" based on given constraints for measured responses. Based on available data for dissolution studies, "overlay plot" as shown in Figure 4 was obtained through graphical optimization.…”