Characterization of Cariprazine Hydrochloride loaded Intranasal Nanoformulation in Simulated Nasal Fluid Using a Validated UV Spectrophotometric Method
Abstract
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
Keywords:
Cariprazine, method development, method validation, simulated nasal fluid, green analysisDOI
https://doi.org/10.22270/jddt.v16i9.8010References
1. Citrome L. Cariprazine: chemistry, pharmacodynamics, pharmacokinetics, and metabolism, clinical efficacy, safety, and tolerability. Expert Opin Drug Metab Toxicol 2013;9(2):193-206. https://doi.org/10.1517/17425255.2013.759211 PMid:23320989
2. Kiss B, Horváth A, Némethy Z, Schmidt É, Laszlovszky I, Bugovics G. RGH-188), a dopamine D3 receptor-preferring D3/D2 receptor antagonist-partial agonist antipsychotic candidate: in vitro and neurochemical profile. J Pharmacol Exp Ther 2010;333(1):328-40. https://doi.org/10.1124/jpet.109.160432 PMid:20093397
3. VRAYLAR® (cariprazine) capsules: Prescribing Information. AbbVie Inc
4. Djupesland PG. Nasal drug delivery devices: characteristics and performance in a clinical perspective-a review. Drug Deliv Transl Res 2013;3(1):42-62. https://doi.org/10.1007/s13346-012-0108-9 PMid:23316447 PMCid:PMC3539067
5. Illum L. Nasal drug delivery-possibilities, problems and solutions. J Control Release 2003;87(1-3):187-98. https://doi.org/10.1016/S0168-3659(02)00363-2 PMid:12618035
6. Snyder LR, Kirkland JJ, Dolan JW. Introduction to Modern Liquid Chromatography. Hoboken: John Wiley & Sons; 2010. https://doi.org/10.1002/9780470508183
7. Toujani E. Development and validation of a stability-indicating high-performance liquid chromatographic assay for determination of cariprazine in bulk form and in drug product. J Pharm Biomed Anal 2022;218.
8. Abu Reid IO. UV‐Vis spectrophotometric determination of multicomponent pharmaceuticals: Limitations, severity‐driven strategies, and method selection. J Spectrosc (Hindawi) 2026;2026(1). https://doi.org/10.1155/jspe/1129092
9. Khan MMG, Raut SR, Usman MRM, Shirkhedkar AA, Alam MS, Khan ZG. Optimization of UV spectrophotometric techniques for tafamidis meglumine detection in pharmaceutical formulations and biological samples: A green chemistry perspective. Ann Pharm Fr 2026;84(1):124-40. https://doi.org/10.1016/j.pharma.2025.08.006 PMid:40825392
10. Dastan K, Enes D, Kaplan O, Dogan A, Celebier M. A comprehensive examination of UV-VIS Spectrophotometric methods in pharmaceutical analysis between 2015-2023. Comb Chem High Throughput Screen 2025;28(7):1125-32. https://doi.org/10.2174/0113862073285152240514171505 PMid:38808707
11. Shinde KP, Rajmane AD. A Review UV Method Development and Validation. Asian Journal of Pharmaceutical Analysis 2023;13(2):122-30. https://doi.org/10.52711/2231-5675.2023.00021
12. Arunagiri T, Ganesan A, Ravi Kumaran V, Masilamani B, Kannaiah KP, Narayanasamy E Thanoon D, et al. Green analytical chemistry-based spectrophotometric techniques for ternary component analysis of pain relievers," Futur. Farmatsiia (Sofia) 2024;10(1):1-6. https://doi.org/10.1186/s43094-024-00648-8
13. Thanoon E, Othman N, AL-Taee A. Green UV-spectrophotometric method for estimation of esomeprazole in injection dosage. Farmatsiia (Sofia) 2025;72:1-6. https://doi.org/10.3897/pharmacia.72.e144399
14. Pena-Pereira F, Wojnowski W, Tobiszewski M. AGREE-Analytical GREEnness metric approach and software. Anal Chem 2020;92(14):10076-82. https://doi.org/10.1021/acs.analchem.0c01887 PMid:32538619
15. Tobiszewski M, Marć M, Gałuszka A, Namieśnik J. Green chemistry metrics with special reference to green analytical chemistry. Molecules 2015;20(6):10928-46. https://doi.org/10.3390/molecules200610928 PMid:26076112 PMCid:PMC6272361
16. Jaiswal SR, Zambre DS, Belgamwar VS. Efficient quantification of Iloperidone in simulated nasal fluid: UV spectrophotometric method development and validation. Curr Anal Chem 2026;22. https://doi.org/10.2174/0115734110439031251218004602
17. Tanigawa H, Suzuki N, Suzuki T. Application of ionic liquid to enhance the nose-to-brain delivery of etodolac. Eur J Pharm Sci 2022;178(106290):106290. https://doi.org/10.1016/j.ejps.2022.106290 PMid:36058500
18. Prasad AR, Thireesha B. UV-Spectrophotometric Method Development And Validation For The Determination Of Lornoxicam In Microsponges. Int J App Pharm 2018;74-8. https://doi.org/10.22159/ijap.2018v10i1.22357
19. Dwi Putri AP, Ilyas N, Abdullah D, Pratama FA, Azzahra KS, Permana AD. Development and validation of UV-Vis spectrophotometric method for determination of rivastigmine in PBS and biological matrices: Application to ex vivo permeation profiles and in vivo studies from trilayer dissolving microneedle. Chemical Data Collections. 2024;49. https://doi.org/10.1016/j.cdc.2023.101106
20. Sharma S, Sharma JB, Bhatt S, Kumar M. Method Development and Validation of UV Spectrophotometric Method for the Quantitative Estimation of Curcumin in Simulated Nasal Fluid. Drug Res (Stuttg) 2020;70(08):356-9. https://doi.org/10.1055/a-1193-4655 PMid:32575135
21. Vancha H, Tewari D, Kumar R, Govindaiah P, Mohd S, Singh SK, et al. Analytical quality by design driven development and validation of UV-visible spectrophotometric method for quantification of xanthohumol in bulk and solid lipid nanoparticles. Turk J Pharm Sci 2023;20(3):165-75. https://doi.org/10.4274/tjps.galenos.2022.05335 PMid:37417199 PMCid:PMC10337025
22. Lambarki LZ, Jhilal F, Slimani L, El Hajji R, Bakkali F, Iskandar S, et al. Comparison of approaches for assessing detection and quantitation limits in bioanalytical methods using HPLC for sotalol in plasma. Sci Rep 2025;15(1):5472. https://doi.org/10.1038/s41598-024-83474-5 PMid:39952988 PMCid:PMC11829023
23. Hammad SF, Rady MM, El-Malla SF. UV spectrophotometric methods for simultaneous determination of ketorolac tromethamine and olopatadine hydrochloride: Application of multiple standard addition for assay of ophthalmic solution. Sci Rep 2023;13(1):18143. https://doi.org/10.1038/s41598-023-45378-8 PMid:37875539 PMCid:PMC10598205
24. Walash MI, El-Enany NM, Saad S. Spectrophotometric determination of certain CNS stimulants in dosage forms and spiked human urine via derivatization with 2,4-Dinitrofluorobenzene. Chem Cent J 2011;5(1):65. https://doi.org/10.1186/1752-153X-5-65 PMid:22032335 PMCid:PMC3239311
25. Tambe S, Das SS, Shahane K, Singh SK, Ruokolainen J, Amin P, et al. First-order derivative spectrophotometric method for simultaneous determination of brinzolamide and timolol maleate in ophthalmic formulation. Green Analytical Chemistry 2024;8(100098):100098. https://doi.org/10.1016/j.greeac.2024.100098
26. Arora D, Kumar M, Bhatt S, Taneja Y, Tiwari A, Tiwari V. UV Spectrophotometric Method for Quantification of Rivastigmine Tartrate in Simulated Nasal Fluid: Development and Validation. Biomedical and Pharmacology Journal 2021;14(4):2165-72. https://doi.org/10.13005/bpj/2314
27. Kaya SI, Ozcelikay-Akyildiz G, Ozkan SA. Green metrics and green analytical applications: A comprehensive outlook from developing countries to advanced applications. Green Analytical Chemistry 2024;11(100159):100159. https://doi.org/10.1016/j.greeac.2024.100159
28. Cetinkaya A, Kaya SI, Ozkan SA. An overview of the current progress in green analytical chemistry by evaluating recent studies using greenness assessment tools. Trends Analyt Chem 2023;168(117330):117330. https://doi.org/10.1016/j.trac.2023.117330
29. Wojnowski W, Tobiszewski M, Pena-Pereira F, Psillakis E. AGREEprep - Analytical greenness metric for sample preparation. Trends Analyt Chem 2022;149(116553):116553. https://doi.org/10.1016/j.trac.2022.116553 PMCid:PMC12837646
30. Voriconazole Loaded Lipidic Nanoparticles for Ophthalmic Delivery: Development Using QbD Combined with Risk-based Approach.
31. Madane RG, Mahajan HS. Curcumin-loaded nanostructured lipid carriers (NLCs) for nasal administration: design, characterization, and in vivo study. Drug Deliv 2016;23(4):1326-34. https://doi.org/10.3109/10717544.2014.975382 PMid:25367836
32. Rahamathulla M, Bindiya R, Venkatesh MP, Pai DR, Harshith HS, Ghazwani M, et al. Design and optimization of intranasal aripiprazole-loaded nanostructured lipid carriers for enhanced brain targeting in schizophrenia: in vitro and ex vivo evaluation. Sci Rep 2025;15(1):45118. https://doi.org/10.1038/s41598-025-32985-w PMid:41429879 PMCid:PMC12748575
33. Harmonisation of Technical Requirement of Registration of Pharmaceuticals for Human Use. Validation of Analytical Procedures: Text and Methodology, Q2B. Geneva, Switzerland: 1996.
34. Syed A, Karwa P, Mohanty A, Srinu. UV spectrophotometric method development and validation for quantitative analysis of cariprazine hydrochloride. Res J Pharm Technol 2025;12(18):6065. https://doi.org/10.52711/0974-360X.2025.00877
35. Chiprikar P, Mastiholimath V. Method Development and Validation of by UV Spectrophotometric Method. Indian Journal of Novel Drug Delivery 2022;14(1):52-57.
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