Development and Optimization of a Nasal in situ Gel for Enhanced Brain Delivery of Safinamide in Parkinson's Disease

Background

Parkinson's Disease (PD) is the second most prevalent neurodegenerative disorder. Currently levodopa along with MAO-B inhibitors remains first line therapy for the management of motor complications. However, its conventional oral dosage forms face significant challenges in achieving effective drug delivery to the target site (the brain) due to the restrictive nature of the blood brain barrier. Strategy involves developing an optimized nasal in situ gel formulation for safinamide to enhance its delivery to the brain.

Materials and Methods

Factorial design was adopted to develop and optimize Safinamide nasal in situ gel. Poloxamer 188 (A: 17.5-30%) and oleic acid (B: 1.25-1.5%) were chosen as the independent variables, while gelling time, mucoadhesive strength, and partition coefficient were designated as the dependent variables.

Results

The formulations were evaluated for various parameters, such as drug content, pH, gelling temperature, viscosity, and in vivo properties. The optimal formulation, S1 (17.5%, 1.25%), achieved a body-temperature-appropriate gelation point of 37.8ºC, while a higher polymer concentration (S9:30% w/w) increased it to 39.3ºC. All gels exhibited a nasal-friendly pH range (7.1-7.5) and high drug content (96.4-99.4).

Conclusion

The results demonstrate that an optimized in situ gelling system shows efficient patient friendly platform and facilitate direct nose-to-brain transport, offering a promising noninvasive strategy for improving safinamide delivery in PD management.