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
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
Conclusion: Overall, the results established that NLCs could be used as a new alternative
delivery vehicle for the oral delivery of ZT.