Characterization of Cariprazine Hydrochloride loaded Intranasal Nanoformulation in Simulated Nasal Fluid Using a Validated UV Spectrophotometric Method

Cariprazine hydrochloride belongs to the third generation atypical antipsychotics and possesses a high potential for intranasal drug delivery. Quantitative analysis of the drug-loaded nanoformulations requires validated methods for measuring drug content in simulated nasal fluid (SNF), which is a physiologically relevant medium employed during intranasal formulation development. No validated UV spectrophotometric methods have been described in the literature for estimating the concentration of cariprazine hydrochloride in SNF. In this work, the goal was to establish, validate and show the feasibility of using a UV spectrophotometric method for estimation of the concentration of cariprazine hydrochloride in SNF. The method was developed using SNF, containing 2% (v/v) methanol as the solvent system with measurement of the absorbance at 244.5 nm. Validation of the proposed method was performed following ICH Q2(R1) recommendations by the assessment of linearity, accuracy, precision, sensitivity, and robustness. The validated method was used to conduct the pharmaceutical evaluation of nanostructured lipid carriers loaded with cariprazine hydrochloride by measurement of entrapment efficiency, in vitro drug release and ex vivo permeation. Environmental sustainability of the method was evaluated by AGREE and AGREEprep criteria. The method demonstrated high linearity with correlation coefficient of R²= 0.9991 within the concentration range of 10-60 µg/ml and regression equation of y = 0.0162x + 0.0028. The obtained percent recovery was 99.90%, and the intra- and inter-day precision %RSD were in the range of 0.072-0.972% and 0.281-1.077%, respectively. Additionally, the method had satisfactory robustness under controlled conditions of analytical variability. The obtained LOD and LOQ values were 1.91 µg/mL and 5.78 µg/mL, respectively. The greenness of the method was confirmed by obtaining AGREE and AGREEprep scores of 0.72 and 0.71, respectively. Besides that, the validated method was successfully used to determine the entrapment efficiency, in vitro drug release and ex vivo permeation of nanostructured lipid carriers of cariprazine hydrochloride, making it a valuable analytical tool for routine intranasal formulation development and quality control. Keywords: Cariprazine, UV spectrophotometry, method development, method validation, simulated nasal fluid, green analysis