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Volume 25, Issue 7
  • ISSN: 1389-2002
  • E-ISSN: 1875-5453

Abstract

Background

Cariprazine (CPZ) is a third-generation antipsychotic medication that has been approved for treating schizophrenia. This study aimed to develop a cariprazine-loaded nanostructured lipid carrier (CPZ-NLCs) to prevent first-pass metabolism and improve bioavailability and site-specific delivery from nose to the brain.

Methods

The CPZ-NLCs were prepared using melt emulsification. The formulation was optimized using the Box–Behnken design (BBD); where the influence of independent variables on critical quality attributes, such as particle size and entrapment efficiency was studied.

Results

The optimized batch (F6) had a particle size of 173.3 ± 0.6 nm and an entrapment efficiency of 96.1 ± 0.57%, respectively. The release showed >96% release of CPZ from NLC within 30 min. The optimized formulation's studies revealed significantly increased CPZ permeability (>75%) in sheep nasal mucosa compared to the CPZ suspension (~26%). The ciliotoxicity study of the nasal mucosa revealed that the CPZ-NLC formulation did not affect the nasal epithelium. The intranasal administration of the formulation achieved 76.14±6.23 µg/ml concentration in the brain which was significantly higher than the oral CPZ suspension administration (30.46±7.24 µg/ml). The developed formulation was stable for 3 months.

Conclusion

The study concluded that the developed CPZ-NLC could significantly improve the bioavailability with quick delivery to the brain.

© 2024 Bentham Science Publishers
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2025-04-15

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Quality by Design Approach for the Development of Cariprazine Hydrochloride Loaded Lipid-Based Formulation for Brain Delivery via Intranasal Route
Current Drug Metabolism 25, 523 (2024); https://doi.org/10.2174/0113892002327148240924071717
/content/journals/cdm/10.2174/0113892002327148240924071717
/content/journals/cdm/10.2174/0113892002327148240924071717
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  • Article Type:     Research Article
Keyword(s): box behnken design; cariprazine; emulsification–ultrasonication technique; Nanostructured lipid carrier; nasal epithelium; nose-to-brain delivery; schizophrenia

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