Background 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. Results 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. Conclusion Therefore, the results concluded that SLNs could be considered as a new alternative delivery system for the enhancement of oral bioavailability of ZT.

Background: Zotepine (ZT) is a substituted dibenzothiepine tricyclic molecule and second generation antipsychotic drug. It is available as the parenteral and oral solid dosage form, but, orally administered ZT has a poor oral bioavailability (10%) that might be due to either poor water solubility, high lipophilicity (Log P 4) and also first-pass hepatic metabolism. Objective: The oral bioavailability of ZT was improved by loading into a nanostructured lipid carriers (NLCs) system. Methods: Hot homogenization with probe sonication method was used for the preparation of ZT-NLCs formulations and characterized for an optimal system based on physicochemical characteristics and in vitro release. Differential scanning calorimetry (DSC), X-ray diffraction (XRD) analysis, and scanning electron microscopy (SEM) studies were used to confirm the crystalline nature and shape of the optimized ZT-NLC formulation. The physical stability of the optimized ZT-NLC formulation was evaluated at the refrigerator and room temperature over two months. Furthermore, in vivo pharmacokinetic (PK) studies of optimized ZT-NLC and ZT coarse suspension (ZT-CS) as control formulation, were conducted in male Wistar rats. Results: The optimized formulation of ZT-NLC showed Z-avg, PDI, ZP of 145.8 ± 2.5 nm, 0.18 ± 0.05, -31.6 ± 1.8 mV, respectively. In vitro release studies indicated the sustained release of ZT. DSC and XRD studies revealed the conversion of ZT into an amorphous form. SEM studies showed the spherical shape of the ZT-NLC formulation. PK studies showed 1.8-folds improvement (p<0.05) in oral bioavailability when compared with ZTCS formulation. Conclusion: Overall, the results established that NLCs could be used as a new alternative delivery vehicle for the oral delivery of ZT.