The purpose of this work was to prepare and evaluate the zotepine (ZT) loaded solid lipid nanoparticles (SLNs) that might improve the oral bioavailability. ZT is an anti-psychotic drug used for the treatment of schizophrenia. Currently, it is available as parenteral and oral dosage form. But, ZT has a poor oral bioavailability of about 7–13% due to limited aqueous solubility and first-pass effect. ZT-SLNs were developed using homogenization method and characterized for optimal system based on physicochemical characteristics and in vitro release. The optimized ZT-SLNs were evaluated for permeation through rat intestine using evert sac method. The crystalline nature of the ZT-SLNs was studied using DSC and XRD analysis. Surface morphology studies were conducted using SEM. Physical stability of the optimized ZT-SLN was evaluated at refrigerator and room temperature over 2 months. Further, pharmacokinetic (PK) studies of ZT-SLN were conducted in male Wistar rats, in comparison with ZT coarse suspension (ZT-CS), in vivo. Among all the developed ZT-SLN formulations, optimized formulation (F1) showed Z-avg, PDI, and ZP of 104.3 ± 1.6 nm, 0.17 ± 0.01, and − 30.5 ± 2.5 mV, respectively. In vitro release and permeation studies exhibited 82.9 ± 1.6% of drug release and 19.6 ± 2.1% of percentage drug permeation over 48 h and 120 min, respectively. DSC and XRD studies revealed the conversion of ZT to amorphous form. SEM studies showed spherical shape with improved PDI of ZT-SLN formulation. PK studies showed a significant (p < 0.05) improvement in AUC of about 1.3-fold, in comparison with ZT-CS in Wistar rats. Therefore, the results concluded that SLNs could be considered as a new alternative delivery system for the enhancement of oral bioavailability of ZT.

中文翻译：

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佐替平负载脂质纳米粒用于口服递送：开发，表征和体内药代动力学研究

这项工作的目的是准备和评估加载佐替平（ZT）的固体脂质纳米颗粒（SLN），这可能会提高口服生物利用度。ZT是用于治疗精神分裂症的抗精神病药。目前，它可以肠胃外和口服剂型形式获得。但是，由于水溶性有限和首过效应，ZT的口服生物利用度较差，约为7–13％。ZT-SLNs是使用均质化方法开发的，并根据理化特性和体外释放对最佳系统进行了表征。使用Evert囊囊法评估了优化的ZT-SLNs通过大鼠肠道的渗透性。ZT-SLNs的晶体性质使用DSC和XRD分析进行了研究。使用SEM进行表面形态研究。优化的ZT-SLN在冰箱和室温下超过2个月的物理稳定性进行了评估。此外，与ZT粗悬液（ZT-CS）相比，在体内对雄性Wistar大鼠进行了ZT-SLN的药代动力学（PK）研究。在所有已开发的ZT-SLN配方中，优化配方（F1）分别显示Z-avg，PDI和ZP分别为104.3±1.6 nm，0.17±0.01和− 30.5±2.5 mV。体外释放和渗透研究在48小时和120分钟内分别显示出82.9±1.6％的药物释放和19.6±2.1％的药物渗透百分比。DSC和XRD研究表明ZT转化为无定形形式。SEM研究显示ZT-SLN配方具有改进的PDI球形。PK研究表明，与Wistar大鼠中的ZT-CS相比，AUC的显着改善（p <0.05）约为1.3倍。因此，