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Published on: November 14, 2018
Quality by Design Approach for the Development of Cariprazine Hydrochloride Loaded Lipid-Based Formulation for Brain
Pallavi Chiprikar1, Vinayak Mastiholimath1, Prakash Biradar2
1Department of Pharmaceutical Quality Assurance, KLE College of Pharmacy, Belagavi, KLE Academy of Higher Education and Research (KAHER), Belagavi, Karnataka, India.
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.
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