Utility of Piperine and Liquisolid Tablets to Enhance the Pharmacological Profile of Tacrolimus
DOI:
https://doi.org/10.22317/jcms.v10i6.1674Keywords:
Tacrolimus; Bioenhancer; Calcineurin inhibitors; Immunosuppressant; Self-nano emulsifying drug delivery system; Liquisolid tabletsAbstract
Objective: To evaluate the impact of a self-nanoemulsifying drug delivery system (SNEDDS) incorporated into liquisolid tablets (LSTs) and the natural bioenhancer piperine (Pip) on the bioavailability, immunosuppressive efficacy, and toxicity of tacrolimus (Tac).
Methods: An optimized Tac-SNEDDS was developed and formulated into four LST compositions using various carriers and coatings (Neusilin®-Avicel®/FujiSil®-fumed silica). The optimal Tac-LST formulation was selected based on drug content and tested in Wistar rats. Bioavailability was assessed using the limited area under the curve (AUC₀₋₆), while immunosuppressive efficacy was evaluated through IL-2 levels. Renal histology and serum cystatin C levels were analyzed to assess potential nephrotoxicity.
Results: Among the four Tac-LST formulations, LST-4 (Avicel®/FujiSil®) exhibited the highest drug content and was chosen for in vivo studies. Co-administration of Pip, LSTs, and their combination significantly improved Tac bioavailability without compromising immunosuppressive activity. Pip co-administration demonstrated superior IL-2 inhibition compared to Tac alone or Tac-LSTs. Additionally, Pip reduced Tac-induced increases in serum cystatin C levels and mitigated renal histological damage, indicating a nephroprotective effect. The combination of Pip and Tac-LSTs provided the most stable absorption profile with minimal AUC fluctuations, suggesting a more predictable pharmacokinetic profile.
Conclusion: Pip and LST formulations significantly enhance Tac bioavailability while maintaining its immunosuppressive efficacy. Moreover, Pip exhibits a protective effect against Tac-induced nephrotoxicity. The combination of Pip and Tac-LSTs offers a stable pharmacokinetic profile, potentially improving therapeutic outcomes by maintaining consistent drug levels.
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