Design expert analysis of tacrolimus compatibility with common excipients.

OBJECTIVE

Tacrolimus is a potent macrolide immunosuppressant widely utilized in solid organ transplantation and the management of autoimmune disorders. The current study aimed to investigate the compatibility of tacrolimus with four commonly used excipients, including sodium croscarmellose, hydroxypropyl methylcellulose (HPMC), magnesium stearate, and lactose monohydrate.

SIGNIFICANCE: The design of Experiments transforms drug-excipient compatibility studies by allowing for a precise, data-driven evaluation of multiple key factors with minimal experimental runs, ensuring reliable formulation development while saving time and resources.

METHODS

A total of 14 experimental runs were generated using Design-Expert® software, incorporating three critical variables: temperature, relative humidity (RH), and drug-to-excipient ratio for each excipient. Tacrolimus was blended with the respective excipients at predetermined ratio and subjected to controlled storage conditions under varying temperature and RH levels. Post-incubation, the residual tacrolimus content was quantified via HPLC. Additionally, to further assess physicochemical interactions, DSC and FT-IR were employed for selected samples.

RESULTS

The model-fitting analysis revealed that all excipients, except HPMC, followed a linear pattern, whereas HPMC exhibited quadratic behavior. In all experimental groups, increasing RH significantly accelerated tacrolimus degradation. Notably, elevated temperature and higher excipient ratio further reduced the remaining drug concentration in all formulations except those containing magnesium stearate. The DSC thermograms revealed no significant alterations. FTIR spectroscopic analysis confirmed that only magnesium stearate-containing formulations exhibited distinct spectral patterns compared to pure tacrolimus.

CONCLUSION

These findings underscore the need for careful consideration when using magnesium stearate in tacrolimus formulations.