Relevance of air-to-liquid mass ratio effect on final granule properties of an Enalapril maleate formulation

Abstract

Background: In the production of enalapril maleate tablets, the granulation process is the most crucial step. Numerous variables are known to influence the fluid bed granulation process and thus the final granule quality. In this study a novel descriptor for the nozzle parameter “air-to-liquid mass ratio” is presented. Granules manufacturing processes were designed by application of statistical experimental design.

Aim: The influence of the critical process parameter (CPP)—air-to-liquid mass ratio—on pharmaceutic properties of granules was studied. Air-to-liquid mass ratio can be considered as important variable influencing the droplet size of atomized liquid binder solution.

Results/Conclusion: A significant influence of air-to-liquid mass ratio on granule final particle size distribution was found. Increasing air-to-liquid mass ratio resulted in increased granules particle size distribution. Decreasing air-to-liquid mass ratio led to granules with reduced tapped density. Thus, it can be concluded that the parameter “air-to-liquid mass ratio” is a critical process parameter in the production of enalapril maleate granules.

Keywords::

• Enalapril maleate formulation; design of experiments
• air-to-liquid mass ratio
• fluid bed granulation
• quality by design