Formulation, characterization, and optimization of aripiprazole-loaded lyotropic liquid crystalline nanoparticle for sustained release and better encapsulation efficiency against psychosis disorder

Abstract

Lyotropic liquid crystalline nanoparticles (LLCNPs) have recently received much attention in the application of drug delivery systems, due to their ordered and versatile internal nanostructures that are considered as a key factor in improving loading efficiency of various poorly soluble therapeutic agents. To take advantage on their unique well-defined and flexible internal nanostructures, aripiprazole-loaded LLCNPs consisted of a binary mixture of soy phosphatidylcholine (SPC) and citric acid ester of monoglyceride (citrem) were developed in this study. Despite exhibiting low aqueous solubility which lead to difficulties in formulation, aripiprazole, a class of psychotropic drug called atypical anti-psychotics has been used in the treatment of schizophrenia and bipolar disorder with few side effects. The utmost interest in this study is to explore the potential of LLCNPs in improving the percentage of encapsulation efficiency (EE%) of aripiprazole, their effect on the internal nanostructure of LLCNPs mesophases as well as the drug release performance from LLCNPs. The particle size of drug-loaded LLCNPs produced was in the range of 161–186 nm, with polydispersity index (PDI) between 0.11–0.16, and negative zeta potential of -21.5 to -23.8 mV. Small-angle X-ray scattering (SAXS) measurements indicated that the internal nanostructures of LLCNPs are of inverse hexagonal (H2) with a negligible difference in the lattice parameter before and after drug loading. Transmission electron microscopy (TEM) was used to observe the morphology and overall size distribution of drug-free and drug-loaded nanodispersions, which supported both SAXS and particles size findings. Differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy demonstrated that aripiprazole interacted physically with binary mixture of citrem/SPC within the nanodispersions. Moreover, the results showed that aripiprazole was successfully encapsulated into LLCNPs nanoparticles, where the EE% was all above 92%. These LLCNPs were not only have a high EE% value, but also exhibited a sustained release performance of aripiprazole with the release capacity of around 97% up to 96 h. From the current study, the potential use of LLCNPs as a promising nanocarrier for aripiprazole delivery is anticipated to improve the pharmacokinetics of this drug whilst enduring the internal nanostructural stability of the LLCNPs upon exposure to physiological environment.