Worldwide Research and Development, Pfizer Inc., Eastern Point Road, Groton, Connecticut 06340, USA.
Pharm Res. 2011 Dec;28(12):3159-70. doi: 10.1007/s11095-011-0505-7. Epub 2011 Jun 15.
To develop and characterize new formulations of ziprasidone with a reduced food effect achieved by increasing exposure in the fasted state.
Formulations were developed utilizing the following solubilization technologies: inclusion complex of ziprasidone mesylate and cyclodextrin, ziprasidone free base nano-suspension, and semi-ordered ziprasidone HCl in polymer matrix. Pharmacokinetic studies were conducted with these formulations to examine the bioavailability of test formulations in fasted and fed state compared to commercial capsules (Geodon®) dosed in the fed state.
All formulations containing solubilized ziprasidone showed either no food effect or a reduced food effect compared to commercial capsules. Two formulations when taken in the fasted or fed state were comparable to the commercial capsules dosed in the fed state with respect to total exposure. However, peak concentrations were ~30-40% higher.
Pharmacokinetic studies indicated solubilization technologies can be employed to successfully increase the extent of ziprasidone absorption in the fasted state, thereby reducing the food effect. Such formulations could provide simple and convenient dosing while retaining the familiar safety and efficacy profile of currently marketed capsules.
开发并表征新的齐拉西酮制剂，通过增加空腹状态下的暴露量来减少食物效应。
利用以下增溶技术开发制剂：甲磺酸齐拉西酮与环糊精的包合物、齐拉西酮游离碱纳米混悬液和聚合物基质中的半有序盐酸齐拉西酮。进行了这些制剂的药代动力学研究，以考察与在进食状态下给药的商业胶囊（Geodon®）相比，测试制剂在禁食和进食状态下的生物利用度。
与商业胶囊相比，所有含有增溶齐拉西酮的制剂均显示出无食物效应或减少的食物效应。两种制剂在禁食或进食状态下与在进食状态下给药的商业胶囊相比，在总暴露量方面具有可比性。然而，峰值浓度高出约 30-40%。
药代动力学研究表明，增溶技术可用于成功增加齐拉西酮在空腹状态下的吸收程度，从而减少食物效应。这些制剂可以提供简单方便的给药方式，同时保留目前市售胶囊熟悉的安全性和疗效特征。
