Trazodone Hydrochloride

Trazodone hydrochloride is a triazolopyridine derivative that acts on 5-HT1 and 5-HT2 serotonergic receptors. The drug also blocks serotonin reuptake and selectively blocks presynaptic receptors. Additionally, trazodone blocks alpha-2 adrenoceptors. Unlike tricyclic antidepressants, trazodone causes fewer anticholinergic side effects and has activity against anxiety concomitant with depression. At therapeutic doses, trazodone is less likely to cause cardiotoxicity than imipramine and does not result in neurologic side effects. The drug is well tolerated by elderly patients. The mechanism of action of trazodone is thought to involve activity at 5-HT1 and 5-HT2 serotonergic receptors, serotonin reuptake blockade, presynaptic receptor blockade, and alpha-2 adrenoceptor antagonism.

Fig. 1 In vitro Trazodone Hydrochloride release from different prepared formulations. (Elhesaisy N, Swidan S. 2020)

A sustained-release drug delivery system containing trazodone hydrochloride was fabricated by combining electrospray technology with functional carriers including Soluplus, Carbopol 940, HPMC K4M and Lecithin. The optimized system exhibited spherical morphology with a particle size of 3.456 ± 0.448 μm, polydispersity index of 0.456 ± 0.024, zeta potential of -17.291 ± 2.351 mV, and high encapsulation efficiency of 97.12 ± 1.82 percent. The system maintained good stability for up to 30 days. In vitro release studies showed that the system followed first-order kinetics in pH 1.2 hydrochloric acid solution and the Higuchi model in pH 6.8 phosphate-buffered saline, with cumulative release reaching 80.81 ± 4.26 percent.
Pharmacokinetic studies in rats demonstrated that the time to reach peak concentration was extended from 0.25 h to 1 h, half-life increased from 1.15 ± 0.17 h to 6.71 ± 0.39 h, and relative bioavailability reached 374.64 percent. The system also prolonged drug distribution in brain tissues while reducing liver distribution, thereby lowering hepatotoxicity risk.

Fig. 2 Preparation and characterization of the sustained-release drug delivery system containing trazodone hydrochloride. (Wang C.; et al. 2025)