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Development of drug alone and carrier-based GLP-1 dry powder inhaler formulations
Ist Teil von
International journal of pharmaceutics, 2022-04, Vol.617, p.121601-121601, Article 121601
Ort / Verlag
Netherlands: Elsevier B.V
Erscheinungsjahr
2022
Quelle
Alma/SFX Local Collection
Beschreibungen/Notizen
[Display omitted]
The study aimed to develop two types of dry powder inhaler (DPI) formulations containing glucagon-like peptide-1(7–36) amide (GLP-1): carrier-free (drug alone, no excipients) and carrier-based DPI formulations for pulmonary delivery of GLP-1. This is the first study focusing on the development of excipient free GLP-1 DPI formulations for inhaled therapy in Type 2 diabetes. The aerosolisation performance of both DPI formulations was studied using a next generation impactor and a DPI device (Handihaler®) at flow rate of 30 L min−1. Carriers employed were either a 10% w/w glycine-mannitol prepared by spray freeze drying or commercial mannitol. Spray freeze dried (SFD) carrier was spherical and porous whereas commercial mannitol carrier exhibited elongated particles (non-porous). GLP-1 powder without excipients for inhalation was prepared using spray drying and characterised for morphology including size, thermal behaviour, and moisture content. Spray dried (SD) GLP-1 powders showed indented/dimpled particles in the particle size range of 1–5 µm (also mass median aerodynamic diameter, MMAD: <5 µm) suitable for pulmonary delivery. Across formulations investigated, carrier-free DPI formulation showed the highest fine particle fraction (FPF: 90.73% ± 1.76%, mean ± standard deviation) and the smallest MMAD (1.96 µm ± 0.07 µm), however, low GLP-1 delivered dose (32.88% ± 7.00%, total GLP-1 deposition on throat and all impactor stages). GLP-1 delivered dose was improved by the addition of SFD 10% glycine-mannitol carrier to the DPI formulation (32.88% ± 7.00%–45.92% ± 5.84%). The results suggest that engineered carrier-based DPI formulations could be a feasible approach to enhance the delivery efficiency of GLP-1. The feasibility of systemic pulmonary delivery of SD GLP-1 for Type 2 diabetes therapy can be further investigated in animal models.