Polymer nanoparticles of [(1-methyl-(S)-4,5-dihydroorotyl)-histidyl-prolinamide] as a potential central nervous system antidepressant formulation and their scale-up studies

In the present study, we explored the potential of [(1-methyl-(S)-4,5-dihydroorotyl)-histidyl-prolinamide] (TA0910) as an antidepressant agent to be delivered through the nasal route. For this, the active agent was formulated in the form of nanoparticles of a biodegradable polymer poly (sebacic anhydride). The polymer was synthesized through melt condensation method and was characterized through FTIR, H¹ NMR, and size exclusion chromatography. The antisolvent precipitation method was employed to prepare drug-loaded poly (sebacic anhydride) nanoparticles. This polymer was selected because its nanoparticles are readily taken up by olfactory and trigeminal nerves due to hydrophobic nature of the polymer and then it shows smooth degradation and hydrolytic erosion from surface which is the requirement of short-term drug release in the olfactory region. The influence of formulation and process parameters on particle size was investigated using dynamic light scattering. Nanoparticle morphology was studied through SEM. Drug-loaded polymeric nanoparticles so formed were separated using a novel method. Drug encapsulation efficiency of nanoparticles was determined using HPLC. Cell line experiments were done to determine the potential cytotoxicity of nanoparticles. The nanoparticle product developed had a mean particle size in the range of 300 to 800 nm. In vitro, drug release studies showed an immediate release of TA0910 from the nanoparticles. Stability study of both lab-scale (6 months), as well as scale-up batch (18 months), showed that the product was stable under frozen conditions (− 20 ºC) in terms of drug content, but particle size increased on stability and percentage of drug release increased during initial time points of the release curve. The formulation described can be used and scaled up successfully at the production level to make a viable commercial product.