Application of Void Forming Index (VFI): Detecting agglomeration of mannitol with different physical properties

Sunao Maruyama¹, Shuichi Ando¹ and Etsuo Yonemochi²

¹Formulation Technology Research Laboratories, Daiichi Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan

²Department of Physical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2-4-41, Ebara, Shinagawa-ku, Tokyo 142-8501, Japan

Summary

Mannitol is a promising candidate carrier for dry powder inhalers (DPIs). However, mannitol tends to form agglomerates by crosslinking between particles at high humidity. In a DPI formulation, fine particles are necessary to deliver the drug substance to the lungs, or to improve aerodynamics of the DPI, though smaller particles tend to form agglomerates. Therefore, in the case of using mannitol as a DPI carrier, controlling the risk of powder agglomeration is important. Here, we have focused on the relationship between agglomeration and pressure drop of the sample. Agglomeration ratio was defined as sample retain on the mesh and Void Forming Index at 4 hours (VFI _{4 h}) was defined as ratio of pressure drop of 4 h purged samples to initial samples. It was apparent that the correlation between the agglomeration ratio and VFI _{4 h} were clearly confirmed rather than that between the agglomeration ratio and other indices such as particle size, Hausner ratio and dispersive surface energy. We therefore propose that the VFI detection is a convenient method for evaluation of powder agglomeration capability not only for mannitol but it is also potentially useful for general DPI formulation development.