• JISHA MOHANAN College of Pharmaceutical Sciences, Government Medical College, Kozhikode 673008, Kerala, India
  • SEENIVASAN PALANICHAMY Sri Ramachandra Faculty of Pharmacy, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai 600116, Tamil Nadu, India
  • ARUL KUTTALINGAM College of Pharmaceutical Sciences, Government Medical College, Kottayam 686008, Kerala, India
  • DAMODHARAN NARAYANASAMY SRM College of Pharmacy, SRM University, Kattankulathur 603203, Tamil Nadu, India



Tacrolimus, β-Cyclodextrin, Inclusion complex, Kneading, Solubility, Sublingual tablet, Fast disintegrating


Objective: The study aimed to prepare and characterize inclusion complexes of tacrolimus with β-cyclodextrin to improve its solubility and to formulate them into sublingual fast disintegrating tablets with a view to bypass the first-pass metabolism.

Methods: Tacrolimus: β-cyclodextrin inclusion complexes (1:1 and 1:2 molar proportions) were prepared using the kneading method. Their characterization was accomplished by determining the drug content, solubility, Attenuated Total Reflection-Infrared Spectroscopy (ATR-IR), Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), and powder X-Ray Diffraction analysis (pXRD). These were then formulated to fast disintegrating tablets and evaluated for precompression as well as post compressional characteristics.

Results: SEM analysis showed the inclusion complexes as rough, non-porous, irregular surfaced aggregate particles. DSC and pXRD analyses confirm the crystallinity change and partial conversion to the amorphous form of the drug in the inclusion complexes. From the solubility studies, it was observed that both the inclusion complexes of 1:2 molar ratio (14.82±0.889 µg/ml) and 1:1 molar ratio (12.72±0.1004 µg/ml) improved the aqueous solubility to greater extents in comparison to that of the pure drug (3.05±0.121 µg/ml). All the tablet formulations showed good precompression and mechanical properties. The inclusion complex loaded tablets exhibited a superior drug release pattern when compared to tablets prepared with tacrolimus alone. The optimized formulation (TT3) showed an in vitro disintegration time of 34.33 s and a percent drug release of 97.87.

Conclusion: The inclusion complex formulation combined with the sublingual route of administration can be expected to result in an improved bioavailability of tacrolimus by increasing its solubility and bypassing first-pass metabolism.


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