Abstract
For pediatric transplant patients, a tacrolimus dosage of less than the standard preparation (0.2 mg) is prescribed. The tacrolimus is prepared as solid dispersion formulation (SDF) to enhance dissolution rate, solubility and oral absorption. Due to potential recrystallizing and decreasing supersaturation under the infl uence of humidity and physical impacts, mixing methods for low-dose tacrolimus using a scoopula have been adopted. However, such methods are time-consuming and may result in inconsistency in quality. Furthermore, it remains unclear if the preparations are uniform with the quality of the SDF maintained throughout the duration of drug use. In this study, we investigated which mixing method yields both uniformity and quality. Mixing methods using a rotation-and-revolution mixing machine (R-&-R mixer), a scoopula, mixing machine and a mortar, respectively, were examined. The preparation mixed by a mixing machine was made uniformly but there was recovery loss after mixing, and the dissolution rate was markedly decreased after 90-day storage in the refrigerator. The dissolution rate of the preparation mixed by a mortar decreased rapidly. The decrease in supersaturated state could be due to re-crystallization. On the other hand, mixing by an R-&-R mixer and a scoopula had the same dissolution profi le and maintained a quality comparable to that of the standardized control even after storage for 90 days. The results indicated that mixing by an R-&-R mixer is the most appropriate method for the preparation of low-dose tacrolimus as it is effi cient and ensures consistent quality.
