Agglomeration of Mesoporous Silica by Melt and Steam Granulation. Part I: A Comparison Between Disordered and Ordered Mesoporous Silica

ABSTRACT The objective of this study was to compare agglomerations by melt and steam granulation of ordered, COK-12, and disordered, Syloid® 244 FP (244), mesoporous silica material. Poloxamer 188 (P188) and polyvinylpyrrolidone K25 (PVP) were chosen as binders for melt and steam granulation, respectively. The poorly water-soluble compound, itraconazole (ITZ), was selected for the development of an immediate-release oral dosage form. Steam granulation resulted in the largest granules, however, the slowest release. Compression behavior and tablet properties of steam-granulated material prepared with COK-12 and 244 were similar. As determined by X-ray powder diffraction, melt granulation resulted in the most ITZ to extract from the pores during processing. However, the enhanced release rate was still maintained when compared with the crystalline form. Moreover, no additional drug extraction was observed following the 6 month storage in 25°C/60% relative humidity (RH) and 40 °C/75%RH. P188 diffraction peaks were present in the 244 melt-granulated material, but disappeared because of the degradation following 1 week in 40°C/75%RH conditions. The differential scanning calorimetry analysis indicated that the degradation of P188 already occurred during the granulation process itself. Based on these results, steam granulation with PVP is the preferred method over melt granulation with P188.