Granulation of ibuprofen/isonicotinamide co-crystals by continuous spray granulator (CTS-SGR)

Abstract

The importance of granulation is paramount for tablet manufacturing, and is based on the fact that granulated powders are characterized by improved flowability, compressibility, segregation, and dust reduction. The aim of this study was to prepare and characterize continuous granules of high drug content by using a continuous-spray granulator (CTS-SGR). Ibuprofen (IBU), a drug of low-flowability, was selected as the model drug. As IBU has a low melting point and cannot easily granulate on its own, we employed isonicotinamide (INA) as a coformer that would allow us to prepare co-crystal granules containing 60 % IBU. The results of the undertaken differential scanning calorimetry and powder X-ray diffraction revealed that the IBU and the INA in the granules formed co-crystals. The granulation conditions affected the particle size and the yield of the granules; in fact, a low air supply temperature, a low atomizing air rate, and a high solution flow rate ensured a high granulation efficiency. Moreover, continuous granulation increased the yields of the formulations compared to those obtained through a short-run granulation, and high yields were obtained after applying a low atomizing air rate. The circularity of the granules exceeded 90 %, and their flowability improved when compared to that of the IBU bulk. The undertaking of dissolution studies revealed no change in the elution amount of IBU as a result of the co-crystallization. Our study shows that it is possible to produce high-content IBU granules in a direct and continuous manner through the co-crystallization of IBU and the use of a CTS-SGR.