title: Pharmacokinetics of orally disintegrating tablets of perphenazine/hydroxypropyl-beta-cyclodextrin inclusion complex in rabbits.
abstract: We investigated the pharmacokinetic behavior of orally disintegrating tablets (ODTs) containing perphenazine/hydroxypropyl-beta-cyclodextrin inclusion complex (PPZ/HP-beta-CD) in rabbits and evaluated their bioequivalence with conventional tablets. In this study, a simple, sensitive and accurate high performance liquid chromatography method was developed for the determination of perphenazine concentration in rabbit plasma. The pharmacokinetic parameters were calculated by non-compartmental methods and the bioequivalence between PPZ/HP-beta-CD ODTs with conventional tablets was determined by calculating 90% confidence interval (CI) for the ratio of logarithmic transformed C(max), AUC(0-t), AUC(0-infinity) values. The pharmacokinetic parameters of test ODTs and reference tablets were as follows: C(max), 82.86 and 62.71 ng/mL; AUC(0-24), 480 and 397.56 ng/mL/h; AUC(0-infinity), 505 and 400.12 ng/mL/h; T(max), 1.04 and 3.83h. The relative bioavailabilities of two formulations for AUC(0-t) and AUC(0-infinity) were 120.77% and 126.37%, respectively. The 90% CI statistical analysis demonstrated the two formulations were not bioequivalence. In conclusion, the ODTs showed faster absorption and higher peak concentration when compared with conventional tablets, which suggests ODTs could be promising oral formulations for PPZ.
authors.affiliation: Department of Pharmaceutics, China Pharmaceutical University, Nanjing, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.forename: Yan-Yu
authors.initials: YY
authors.lastname: Xiao
authors.forename: Ming-Lei
authors.initials: ML
authors.lastname: Chen
authors.forename: Fan
authors.initials: F
authors.lastname: Zeng
authors.forename: Li
authors.initials: L
authors.lastname: Zong
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002138:Calibration; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D005079:Excipients; D057230:Limit of Detection; D008297:Male; D010546:Perphenazine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011817:Rabbits; D015203:Reproducibility of Results; D012995:Solubility; D012996:Solutions; D013607:Tablets; D013810:Therapeutic Equivalency; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D014150:Antipsychotic Agents; D005079:Excipients; D012996:Solutions; D013607:Tablets; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D010546:Perphenazine