title: Formulation and in vivo evaluation of orally disintegrating tablets of clozapine/hydroxypropyl-β-cyclodextrin inclusion complexes.
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.
authors: School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
authors: Fan
authors: F
authors: Zeng
authors: Ling
authors: L
authors: Wang
authors: Wenjing
authors: W
authors: Zhang
authors: Kejing
authors: K
authors: Shi
authors: Li
authors: L
authors: Zong
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000284:Administration, Oral; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003024:Clozapine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D018360:Crystallography, X-Ray; D004337:Drug Carriers; D008297:Male; D033362:Powder Diffraction; D011817:Rabbits; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D014150:Antipsychotic Agents; D004337:Drug Carriers; D013607:Tablets; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D003024:Clozapine
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