Quality by Design Approach for the Development of Cariprazine Hydrochloride Loaded Lipid-Based Formulation for Brain Delivery via Intranasal Route.

Autor:	Chiprikar P; Department of Pharmaceutical Quality Assurance, KLE College of Pharmacy, Belagavi, KLE Academy of Higher Education and Research (KAHER), Belagavi, Karnataka, India., Mastiholimath V; Department of Pharmaceutical Quality Assurance, KLE College of Pharmacy, Belagavi, KLE Academy of Higher Education and Research (KAHER), Belagavi, Karnataka, India., Biradar P; Department of Pharmacology, KLE College of Pharmacy, Belagavi, KLE Academy of Higher Education and Research (KAHER), Belagavi, Karnataka, India., Shirkoli N; Department of Pharmaceutical Quality Assurance, KLE College of Pharmacy, Belagavi, KLE Academy of Higher Education and Research (KAHER), Belagavi, Karnataka, India.
Jazyk:	angličtina
Zdroj:	Current drug metabolism [Curr Drug Metab] 2024; Vol. 25 (7), pp. 523-541.
DOI:	10.2174/0113892002327148240924071717
Abstrakt:	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 in vitro release showed >96% release of CPZ from NLC within 30 min. The optimized formulation's ex vivo 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. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu