Physiochemical Properties of Generic Formulations of Tacrolimus in Mexico

Tacrolimus is an important immunosuppressive agent used to prevent allograft rejection after transplantation. Tacrolimus has a narrow therapeutic index; therefore, it is essential that the physicochemical properties of generic formulations be identical to the brand-name formulation, Prograf. In this study, the physicochemical properties of generic tacrolimus formulations were compared with Prograf. The drug dissolution profiles of generic formulations of tacrolimus were different from that of Prograf. Tacrobell and T-Inmun exhibited faster dissolution than Prograf, and Tenacrine, Framebin, and Talgraf showed slower and incomplete drug dissolution, releasing 24% to 51% of tacrolimus within 2 hours. Generic formulations of tacrolimus demonstrated decreased solubility compared with Prograf. The solubility of Prograf was 35.7 microg/mL at 2 hours and 29.5 microg/mL at 24 hours. The solubility of Tenacrine, Framebin, and Talgraf at 2 hours was 5.5, 12.6, and 7.8 microg/mL, respectively, and the solubility decreased to 0.5, 2.3, and 2.1 microg/mL, respectively, at 24 hours. Whereas Prograf demonstrated content uniformity, the content of the generic tacrolimus formulations varied widely. The standard deviation of content for Tenacrine, Tacrobell, and T-Inmun were high at 29.3, 6.9, and 5.6, respectively. Furthermore, the mean percentage of labeled amount of T-Inmun was 84.2% with a relative standard deviation of 6.7% (minimum value; 72.7%; maximum value; 100.7%). These results indicate that generic formulations of tacrolimus tested in this study are not bioequivalent to Prograf, which suggests that their use may be of potential risk to transplant patients.