A levodopa dry powder inhaler for the treatment of Parkinson's disease patients in off periods

作者：Luinstra Marianne^*; Grasmeijer Floris; Hagedoorn Paul; Moes Jan Reindert; Frijlink Henderik W; de Boer Anne H

来源：European Journal of Pharmaceutics and Biopharmaceutics, 2015, 97: 22-29.

DOI：10.1016/j.ejpb.2015.10.003

• Levodopa
• Parkinson's disease
• Off period
• Dry powder inhalation
• Cyclops

Adequate treatment of Parkinson's patients in off periods with orally administered levodopa is hindered by a poor bioavailability and a slow onset of action. Hence, there is a need for a fast and reliable alternative as for instance via pulmonary administration of the drug. We developed a levodopa containing powder formulation for pulmonary delivery by a recently presented high dose dry powder inhaler (Cyclops). The objective was to produce the drug formulation by means of simple techniques such as micronization, either as pure active substance or with a minimum amount of excipients. After an initial screening on dispersion behaviour, the most promising formulation in the Cyclops was characterized in vitro over a range of pressure drops (2-6 kPa) and doses (20, 30 and 40 mg), representative of those to be expected in practice. A co-micronized levodopa formulation with 2% L-leucine appeared to yield the best aerosol properties for inhalation and highest delivered dose reproducibility. The combination of this particular formulation and the Cyclops inhaler seems to meet the basic requirements for satisfactory deposition in the airways. This formulation is therefore expected to be a promising candidate for the treatment of Parkinson's patients in an off period.

• 出版日期2015-11