ABSTRACT
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.
