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Formulation and In Vivo Evaluation of Orally Disintegrating Tablets of Clozapine/Hydroxypropyl-β-cyclodextrin Inclusion Complexes

AAPS PharmSciTech volume 14, pages 854–860 (2013)Cite this article

Abstract

The aim of this study was to improve the solubility and oral bioavailability of clozapine (CLZ), a poorly water-soluble drug subjected to substantial first-pass metabolism, employing cyclodextrin complexation technique. The inclusion complexes were prepared by an evaporation method. Phase solubility studies, differential scanning calorimetry, X-ray powder diffraction, and Fourier transform infrared spectroscopy were used to evaluate the complexation of CLZ with hydroxypropyl-β-cyclodextrin (HP-β-CD) and the formation of true inclusion complexes. Characterization and dissolution studies were carried out to evaluate the orally disintegrating tablets (ODTs) containing CLZ/HP-β-CD complexes prepared by direct compression. Finally, the bioavailability studies of the prepared ODTs were performed by oral administration to rabbits. The ODTs showed a higher in vitro dissolution rate and bioavailability compared with the commercial tablets. It is evident from the results herein that the developed ODTs provide a promising drug delivery system in drug development, owing to their excellent performance of a rapid onset of action, improved bioavailability, and good patient compliance.

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ACKNOWLEDGMENTS

The authors are grateful to the College Students Innovation Project for the R&D of Novel Drugs (program no. J1030830) for supporting the present research work.

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  1. School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China

    Fan Zeng, Ling Wang, Wenjing Zhang, Kejing Shi & Li Zong

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  1. Fan Zeng
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Correspondence to Li Zong.

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Zeng, F., Wang, L., Zhang, W. et al. Formulation and In Vivo Evaluation of Orally Disintegrating Tablets of Clozapine/Hydroxypropyl-β-cyclodextrin Inclusion Complexes. AAPS PharmSciTech 14, 854–860 (2013). https://doi.org/10.1208/s12249-013-9973-x

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KEY WORDS

  • bioavailability
  • clozapine
  • hydroxypropyl-β-cyclodextrin
  • inclusion complexes
  • orally disintegrating tablets