A levodopa with l-leucine inhalation powder for use in Parkinson’s disease

M Luinstr , F Grasmeijer, P Hagedoorn, HW Frijlink, AH de Boer

Parkinson’s disease is a progressive neurodegenerative disorder characterised by degeneration of the dopaminergic neurons in the substantia nigra, causing a lack of dopamine in the striatum. This lack of dopamine causes disruption of motor circuits in the brain resulting in motor function impairments like tremor, rigidity and bradykinesia. Adequate treatment of Parkinson’s patients in off periods with orally administered levodopa is thus hindered by a poor bioavailability and a slow onset of effect. Consequently there is a need for a fast and reliable alternative as for instance via pulmonary administration of the drug. We studied the dispersion performance and retention behaviour of various levodopa dry powder formulations in a recently developed high dose inhaler (Cyclops). The in vitro deposition of the most suitable levodopa dry powder formulation was measured at different pressure drops across the inhaler as well as for different dose levels. The objective was to produce a levodopa inhalation powder by means of very simple techniques such as micronisation, either as pure active substance or with the least possible amount of a safe excipient. Levodopa co-micronised with only 2% l-leucine and dispersed with the Cyclops high dose dry powder inhaler appears to be a promising candidate for the treatment of Parkinson’s disease patients in an off period. The combination of this particular formulation and inhaler meets the basic in vitro requirements regarding emission rate, dispersion efficiency and consistency of delivered dose for satisfactory drug delivery to the peripheral airways.

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