title: Formulation, stability and pharmacokinetics of sugar-based salmon calcitonin-loaded nanoporous/nanoparticulate microparticles (NPMPs) for inhalation.
abstract: A challenge exists to produce dry powder inhaler (DPI) formulations with appropriate formulation stability, biological activity and suitable physicochemical and aerosolisation characteristics that provide a viable alternative to parenteral formulations. The present study aimed to produce sugar-based nanoporous/nanoparticulate microparticles (NPMPs) loaded with a therapeutic peptide - salmon calcitonin (sCT). The physicochemical properties of the powders and their suitability for pulmonary delivery of sCT were determined. Production of powders composed of sCT loaded into raffinose or trehalose with or without hydroxypropyl-β-cyclodextrin was carried out using a laboratory scale spray dryer. Spray dried microparticles were spherical, porous and of small geometric size (≤2 μm). Aerodynamic assessment showed that the fine particle fraction (FPF) less than 5 μm ranged from 45 to 86%, depending on the formulation. The mass median aerodynamic diameter (MMAD) varied between 1.9 and 4.7 μm. Compared to unprocessed sCT, sCT:raffinose composite systems presented a bioactivity of approximately 100% and sCT:trehalose composite systems between 70-90% after spray drying. Storage stability studies demonstrated composite systems with raffinose to be more stable than those containing trehalose. These sugar-based salmon calcitonin-loaded NPMPs retain reasonable sCT bioactivity and have micromeritic and physicochemical properties which indicate their suitability for pulmonary delivery. Formulations presented a similar pharmacokinetic profile to sCT solution. Hence the advantage of a dry powder formulation is its non-invasive delivery route and ease of administration of the sCT.
authors: School of Pharmacy and Pharmaceutical Sciences, Trinity College, University of Dublin, Dublin 2, Ireland. Electronic address: amarom@tcd.ie.
authors: Maria Inês
authors: MI
authors: Amaro
authors: School of Pharmacy and Pharmaceutical Sciences, Trinity College, University of Dublin, Dublin 2, Ireland; INSERM ERI-23, Pôle Biologie-Santé, Faculté de Médecine & Pharmacie, Université de Poitiers, 40 av. du Recteur Pineau,86022 Poitiers Cedex, France.
authors: Frederic
authors: F
authors: Tewes
authors: School of Pharmacy and Pharmaceutical Sciences, Trinity College, University of Dublin, Dublin 2, Ireland.
authors: Oliviero
authors: O
authors: Gobbo
authors: School of Pharmacy and Pharmaceutical Sciences, Trinity College, University of Dublin, Dublin 2, Ireland.
authors: Lidia
authors: L
authors: Tajber
authors: School of Pharmacy and Pharmaceutical Sciences, Trinity College, University of Dublin, Dublin 2, Ireland.
authors: Owen I
authors: OI
authors: Corrigan
authors: School of Pharmacy and Pharmaceutical Sciences, Trinity College, University of Dublin, Dublin 2, Ireland.
authors: Carsten
authors: C
authors: Ehrhardt
authors: School of Pharmacy and Pharmaceutical Sciences, Trinity College, University of Dublin, Dublin 2, Ireland.
authors: Anne Marie
authors: AM
authors: Healy
mesh_terms: D000280:Administration, Inhalation; D002116:Calcitonin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D002241:Carbohydrates / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D004355:Drug Stability; D058995:Dry Powder Inhalers; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D016062:Porosity; D013499:Surface Properties
chemical_list: D002241:Carbohydrates; C028815:salmon calcitonin; D002116:Calcitonin
keywords: Inhalation; Non-reducing sugars; Pharmacokinetics; Salmon calcitonin; Stability