The
tricyclic antidepressant amoxapine (AMX) has been
reported
for a rapid onset of action compared to other cyclic antidepressants.
It has very low solubility and bioavailability due to first-pass metabolism.
Therefore, we planned to develop solid lipid nanoparticles (SLNs)
of AMX using a single emulsification method to increase its solubility
and bioavailability. HPLC and LC-MS/MS methods were developed further
to quantify AMX in the formulation, plasma, and brain tissue samples.
The formulation was studied for entrapment efficiency, loading, and
in vitro drug release. Particle size and ζ potential analyses,
AFM, SEM, TEM, DSC, and XRD were used for further characterization.
In vivo oral pharmacokinetic and brain pharmacokinetic studies were
performed using Wistar rats. The entrapment and loading efficiencies
of AMX in SLNs were 85.8 ± 3.42 and 4.5 ± 0.45%, respectively.
The developed formulation had a mean particle size of 151.5 ±
7.02 nm and a polydispersity index of 0.40 ± 0.11. DSC and XRD
results indicated that AMX was incorporated into the nanocarrier system
in an amorphous form. SEM, TEM, and AFM studies of AMX-SLNs confirmed
the particles’ spherical shape and nanoscale size. AMX solubility
increased by approx. 2.67 times compared to the pure drug. The developed
LC-MS/MS method was successfully applied to the oral and brain pharmacokinetic
study of AMX-loaded SLNs in rats. Oral bioavailability was enhanced
1.6 times compared to the pure drug. The peak plasma concentrations
of pure AMX and AMX-SLNs were 617.4 ± 137.4 and 1043.5 ±
150.2 (ng/mL), respectively. AMX-SLNs showed more than 5.8 times brain
concentration compared to the pure drug. Based on the findings, it
appears that utilizing a solid lipid nanoparticle carrier to transport
AMX can be a highly effective delivery method with improved pharmacokinetic
properties in the brain. This approach may prove valuable for future
antidepressant treatment.