Generation and Characterization of Hexamethylmelamine Aerosols

Abstract

Hexamethylmelamine (HMM) is a well-known active drug for the treatment of human bronchial carcinoma. However, there is no well-established method for administering the drug other than the oral route. In this study novel methods for generation and characterization of HMM aerosols, in vitro, have been developed. The regional deposition of therapeutic aerosols in the human airways is a function of the aerodynamic diameter (Da) of the drug particles and is dependent upon the dimension, density and shape of the particles. In this work, it is shown that elongated particles (e.g. fibres) containing the same mass of the drug as the equivalent spherical particles would deposit deeper in the respiratory tract. Crystal habit modification studies using twenty-two different organic solvents show that the physical properties of the solvent (specifically dielectric constant and dipole moment) are of vital importance in controlling the habits of HMM. Hexagonal, spherical and fibrous particles in the respirable range (≅3.6 um) have been prepared. A new aerosol generator based on homogeneous condensation of HMM vapour was designed. It was successfully used in producing a metastable solid form of the spherical drug particles, which possesses higher solubility than the parent HMM. Techniques based on a modified compressed air nebulizer and a vertical spinning disc powder disperser have been used in the generation of HMM aerosols of different particle shapes. The different crystal habits, new metastable form and aerosols of HMM have been characterized using the following techniques: m.p., density, microscopic examination, C.H.N. microanalysis, spectroscopic measurements, GLC, thermal analysis, solubility measurements and impaction method. New theoretical expressions for the calculation of Da for fibrous particles have been derived and compared with previous theories and experimental results. This work concludes that the preparation of HMM particles of different shapes can be an effective method for designing their aerodynamic properties.