Farsan Rahman1, Julie-Ann Penton1, Daniel Ledger2 & Steven Nicholson2
1 Therakind Limited, 314 Regents Park Rd, London, N3 2JXL, UK
2Crystec Limited, Norcroft Building, Richmond Road, Bradford, BD7 1DP, UK
Summary
Oral levodopa remains the primary treatment for Parkinson’s disease (PD) but is limited by variable absorption and plasma fluctuations, often causing debilitating symptom re-emergence known as “off” episodes. Nasal delivery presents an attractive alternative with the potential to offer rapid absorption, nose-to-brain transport, improved bioavailability and more stable plasma concentrations. This study investigated the feasibility of developing a levodopa dry powder nasal product.
An excipient-free levodopa powder with highly crystalline morphology was successfully engineered using a modified supercritical anti-solvent process. Combined with a novel multi-dose dry powder nasal device, the powder consistently delivered high doses (~35 mg per actuation) with content uniformity within 2% of the metered dose. Particle size distribution analysis confirmed performance within the target nasal deposition range (10–150 µm) containing minimal fine particles (<10 µm) that lead to pulmonary deposition. Overall, this study supported the feasibility of a nasal levodopa combination product candidate capable of reliably delivering high doses with appropriate particle characteristics for nasal absorption and warrants further investigation for managing “off” episodes in PD patients.