title: A levodopa dry powder inhaler for the treatment of Parkinson's disease patients in off periods.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands; Department of Clinical Pharmacy, Martini Hospital, Van Swietenplein 1, 9728 NT Groningen, The Netherlands. Electronic address: m.luinstra@mzh.nl.
authors.forename: Marianne
authors.initials: M
authors.lastname: Luinstra
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Floris
authors.initials: F
authors.lastname: Grasmeijer
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Hagedoorn
authors.affiliation: Department of Clinical Pharmacy, Martini Hospital, Van Swietenplein 1, 9728 NT Groningen, The Netherlands.
authors.forename: Jan Reindert
authors.initials: JR
authors.lastname: Moes
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Henderik W
authors.initials: HW
authors.lastname: Frijlink
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Anne H
authors.initials: AH
authors.lastname: de Boer
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004305:Dose-Response Relationship, Drug; D058995:Dry Powder Inhalers; D005079:Excipients / Q000737:chemistry*; D006801:Humans; D007930:Leucine / Q000737:chemistry; D007980:Levodopa / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010300:Parkinson Disease / Q000188:drug therapy*; D015203:Reproducibility of Results; D014018:Tissue Distribution
chemical_list: D000336:Aerosols; D000978:Antiparkinson Agents; D005079:Excipients; D007980:Levodopa; D007930:Leucine
keywords: Cyclops; Dry powder inhalation; Levodopa; Off period; Parkinson’s disease