Influence of granulation and compaction on the particle size of ibuprofen--development of a size analysis method

Abstract

The aim of this work was to study the impact of the process on drug particle size. We chose ibuprofen, practically insoluble in water, as granulometry greatly influences its dissolution rate. We developed an original method using a laser granulometer to assess the size of ibuprofen within a blend before and after granulation and then compression. Wet granulation was performed with a Lodige and a Diosna granulator. The granules were then compressed. The evolution of ibuprofen particle size after these operations was checked. Two grades of ibuprofen differing in size were studied: ibuprofen 25 and ibuprofen 50. After the wet granulation of ibuprofen 50 with a Lodige or a Diosna granulator, a decrease in size was observed. This could be caused by shocks occurring in the granulator. On the other hand, after compression of the granules, ibuprofen particle size increased and was greater than that measured before granulation. Compression could induce some fragmentation of ibuprofen associated with the plastic deformation and then, under pressure, a closeness of the fragments or deformed particles which could bind or associate with one another because the melting point of ibuprofen is not very high. In the case of ibuprofen 25, the same phenomena were observed after compression. But, after granulation, particle size was not modified. There was little breaking of ibuprofen particles in the granulator because they are much smaller than those of ibuprofen 50. This work shows the impact of the process on drug particle size when producing tablets. The method developed made it possible to differentiate and measure the size of ibuprofen particles in a blend.