Title:Quality by Design Approach for the Development of Cariprazine Hydrochloride Loaded Lipid-Based Formulation for Brain Delivery via Intranasal Route
Volume: 25
Issue: 7
Author(s): Pallavi Chiprikar*, Vinayak Mastiholimath*, Prakash Biradar and Nisha Shirkoli
Affiliation:
- Department of Pharmaceutical Quality Assurance, KLE College of Pharmacy, Belagavi, KLE Academy of Higher Education and
Research (KAHER), Belagavi, Karnataka, India
- Department of Pharmaceutical Quality Assurance, KLE College of Pharmacy, Belagavi, KLE Academy of Higher Education and
Research (KAHER), Belagavi, Karnataka, India
Keywords:
Nanostructured lipid carrier, nose-to-brain delivery, cariprazine, box behnken design, emulsification–ultrasonication technique, schizophrenia, nasal epithelium.
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.
Method: 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.
Result: 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.< /p>
