Microcrystalline cellulose, a useful alternative for sucrose as a matrix former during freeze-drying of drug nanosuspensions - a case study with itraconazole.

摘要

Itraconazole nanosuspensions, stabilized with 10% TPGS (relative to the weight of itraconazole), were transformed into nanoparticulate powders by freeze-drying. The crystalline itraconazole nanoparticles showed peak broadening in the X-ray powder diffraction spectra and a lower melting point as inferred from differential scanning calorimetry. As it was found that freeze-drying compromised dissolution behavior, sucrose was added as a matrix, former (50,100 and 200%, relative to the weight of itraconazole). Higher amounts of sucrose unexpectedly resulted in a decrease in the dissolution rate. After thorough evaluation of the powders, it was found that whereas higher sucrose content showed a cryoprotective effect, agglomeration during the final phase of the subsequent drying step tended to increase with higher amounts of sucrose. Therefore, microcrystalline cellulose (MCC) was evaluated as an alternative matrix former. The inclusion of MCC resulted in fast dissolution that increased with increasing amounts of MCC [for powders containing 50%,100% and 200% MCC, (relative to the weight of itraconazole), the times required for 63.2% release were 10.5+/-0.7, 6.4+/-1.2 and 3.1+/-0.5min, respectively]. The dissolution profiles showed an initial phase of burst dissolution, followed by a phase of slower release. As the fraction showing burst dissolution increased with higher MCC content, the system holds promise to maintain the dissolution enhancing properties of nanoparticles in the dry form.