Innovative Approaches in Levodopa Nasal Spray Formulation: A Review on Excipient Role and Selection

Levodopa, a metabolic precursor of dopamine, is the primary treatment for Parkinson’s disease (PD). However, oral administration faces challenges such as extensive first-pass metabolism, low bioavailability, and erratic absorption, leading to motor fluctuations and reduced therapeutic efficacy. Nasal drug delivery offers a promising alternative by bypassing the gastrointestinal tract and enabling direct nose-to-brain transport through the olfactory and trigeminal pathways. This route facilitates rapid drug absorption, reduces systemic side effects, and improves bioavailability. The development of an optimized levodopa nasal spray requires careful selection of excipients, including solubilizers, permeation enhancers, mucoadhesive agents, and stabilizers, to enhance solubility, permeability, and retention in the nasal cavity. Emerging formulation strategies such as nanoparticle-based systems, in situ gelling formulations, and powder-based nasal sprays further improve drug stability and patient compliance. Despite its advantages, levodopa nasal delivery faces challenges such as enzymatic degradation, mucosal irritation, and variability in nasal absorption. Advances in formulation technologies and clinical studies are crucial for overcoming these barriers and achieving regulatory approval. With continued research, levodopa nasal spray has the potential to become a more effective and patient-friendly alternative to oral therapy, improving symptom management and quality of life for Parkinson’s patients.