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UniORV, a New Multi-Unit Dosage Form, Improved Biopharmaceutical Properties of Tacrolimus in Rats and Humans

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Abstract

Purpose

The aim of the present study was to develop a new multi-unit dosage formulation, Universal ORbicular Vehicle (UniORV), to improve the biopharmaceutical properties of tacrolimus (TAC).

Methods

TAC-loaded UniORV (UO/TAC) was produced by the dripping and gelling of a solution comprising TAC, gelatin, starch syrup, and triethyl citrate at 0.5 w/w% drug loading. Its microstructure was elucidated by polarized light microscopy and the Raman mapping technique. The pharmacokinetic profiles of TAC after the oral administration of UO/TAC were evaluated in rats and healthy humans.

Results

The dissolution behavior of UO/TAC was similar to that of commercial capsules, and the formation of nanoparticles was detected by TEM in dissolved media. In a stability study on UO/TAC, only 2.6 and 4.7% decreases in TAC concentrations were observed at 40± 2°C/75 ± 5% relative humidity for 4 months and at 50± 2°C for 2 months, respectively. A pharmacokinetic study on rats revealed a 30-fold higher AUC than that with crystalline TAC. A randomized double-blind crossover study on 8 healthy males showed that UniORV achieved a 1.4-fold increase in AUC and 34% decrease in inter-individual variation from the reference formulation.

Conclusion

The new dosage form UniORV is a promising approach to improve the dissolution, amorphous stability, and biopharmaceutical properties of TAC, which is a poorly water-soluble drug.

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Acknowledgments and Disclosures

This work was supported in part by a Grant-in-Aid for Scientific Research (C) (No. 17 K08453; S. Onoue) and Young Scientists (18 K14885, H. Sato) from Japan Society for Promotion of Science (JSPS).

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Authors and Affiliations

  1. Sunsho Pharmaceutical Co., Ltd., 533-2, Ooiwa, Fujinomiya, Shizuoka, 418-0013, Japan

    Wataru Hirasawa, Shunsuke Sei, Misuzu Mineda, Norimasa Endo & Yoshiharu Matahira

  2. Laboratory of Biopharmacy, School of Pharmaceutical Science, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan

    Wataru Hirasawa, Keisuke Makino, Ryota Tsukada, Hideyuki Sato & Satomi Onoue

Authors
  1. Wataru Hirasawa
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  2. Shunsuke Sei
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  3. Misuzu Mineda
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  4. Norimasa Endo
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  5. Yoshiharu Matahira
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  6. Keisuke Makino
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  9. Satomi Onoue
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Correspondence to Satomi Onoue.

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Hirasawa, W., Sei, S., Mineda, M. et al. UniORV, a New Multi-Unit Dosage Form, Improved Biopharmaceutical Properties of Tacrolimus in Rats and Humans. Pharm Res 37, 64 (2020). https://doi.org/10.1007/s11095-020-02785-0

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  • DOI: https://doi.org/10.1007/s11095-020-02785-0

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