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

Abstract

This study is the second in a series that examines the characterizing and selection of suitable grades of lactose for capsule formulation development. Based upon the previous study, four grades were selected for further study. The effects of drug load and operational variables on formulations derived from these four lactose types were evaluated for physicochemical and mechanical attributes of plugs and their capsules on an instrumented dosing-disc capsule filling machine (H&H KFM/3) using acetaminophen as a model, highly soluble and poorly compressible drug. The results obtained were as follows: (1) flowability reduced upon increasing drug load; (2) powder bed height (PBH) and compression force (CF) had positive significant effect on plug weight (p < 0.05); (3) ejection force was positively and significantly correlated with increasing speed and CF (p < 0.05); (4) AL capsule plugs had the highest plug crushing force which was followed by DCL15; (5) the crushing strength of plugs made from DCL11 increased with increasing acetaminophen concentration; (6) higher CF had a significant negative impact on acetaminophen release at 15 min time point (p < 0.05); (7) at 10% and 40% drug load, formulations containing AL showed the quickest drug release; and (8) increased drug load had a significant negative impact on the release rate at 15 and 45 min time points (p < 0.05). Overall, the results from this study provides information on risk based assessment of filler selection based on drug load and the range of machine operating variables which will help in defining criteria for meeting key quality attributes for capsule formulation development.

• Capsule filling
• drug dissolution
• ejection force
• formulation development
• lactose
• machine operating variables
• plug crushing strength
• plug weight variation

Acknowledgements

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

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.