Nanonized carbamazepine for nose-to-brain delivery: pharmaceutical formulation development

Area of Science:

• Pharmaceutical Sciences
• Nanotechnology
• Neuroscience

Background:

• Epilepsy is a common neurological disorder with challenging treatment due to conventional drug limitations.
• Intranasal administration offers a direct pathway for drug delivery to the brain.
• Carbamazepine (CBZ), an anticonvulsant, suffers from poor water solubility, hindering its bioavailability.

Purpose of the Study:

• To design and develop carbamazepine nanocrystals (NCs) for effective nose-to-brain delivery.
• To optimize the formulation using a Quality by Design approach.
• To evaluate the physicochemical and preliminary biological properties of the CBZ NCs.

Main Methods:

• CBZ NCs were prepared using the sonoprecipitation technique.
• Quality by Design and response surface methodology were employed for optimization.
• Characterization included thermotropic behavior, crystallinity, morphology, and mucoadhesive strength.
• Biocompatibility was assessed using Olfactory Ensheating Cells.

Main Results:

• Optimized CBZ NCs achieved a size of ≤300 nm with high reliability (2.6% error).
• The nanocrystal formulation demonstrated good stability in artificial cerebrospinal fluid without aggregation or degradation.
• Preliminary studies confirmed the biocompatibility of CBZ NCs with Olfactory Ensheating Cells.
• The formulation was successfully converted into a powder, enabling high drug concentration in a low volume.

Conclusions:

• CBZ nanocrystals are a promising formulation for direct nose-to-brain delivery.
• This approach enhances carbamazepine bioavailability and offers a potential improvement in epilepsy management.
• The developed formulation is stable, biocompatible, and suitable for high-dose administration.