title: Development and evaluation of a dry powder formulation of liposome-encapsulated oseltamivir phosphate for inhalation.
abstract: This study aims to develop oseltamivir phosphate (OP) liposomes as inhalation powders by spray-drying based on the single factor investigation, which was mainly composed of lactose, L-leucine and mannitol. It was found that the ratio of OP and liposomes (1:10), inlet temperature (110 °C) and airflow rate (2.3 mL/min) showed optimized physical properties of OP liposomes. Deposition was evaluated after the aerosolization of powders at 600 L/h via the Aerolizer® into a twin-stage impinger. The concentrations of OP and oseltamivir carboxylate (OSCA) in rats plasma using LC-MS have been determined and performed via pharmacokinetic software DAS 2.0 package. The liposomal OP dry powders displayed an average particle size around 3.5 µm with fine particle fraction (FPF = 35.40%). In vitro evaluation demonstrated a sustained release pattern accounting for 20% drug release compared to that of OP solution up to 90% drug release in 2 h. And the cumulative release percentage was up to 50% in 20 h. Atrioventricular fitting results indicated that all preparations were best fitted with a two-compartment model. There was a significant difference in MRT, Cmax and Tmax (p < 0.01) between the two groups of liposomal OP dry powders and OP solution with t-test, which indicated that the drug released slowly from liposomal OP dry powders in the lung. To sum up, dry powders formulation of liposome-encapsulated OP for inhalation was suitable for pulmonary administration, which offering the opportunity to reduce dosing frequency.
authors.affiliation: Department of Pharmacy, China Pharmaceutical University , Nanjing , People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Tang
authors.forename: Heyang
authors.initials: H
authors.lastname: Zhang
authors.forename: Xifeng
authors.initials: X
authors.lastname: Lu
authors.forename: Liqun
authors.initials: L
authors.lastname: Jiang
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Xi
authors.forename: Jianping
authors.initials: J
authors.lastname: Liu
authors.forename: Jiabi
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D058995:Dry Powder Inhalers; D007785:Lactose; D007930:Leucine; D008081:Liposomes / Q000737:chemistry / Q000493:pharmacokinetics*; D008353:Mannitol; D013058:Mass Spectrometry; D053139:Oseltamivir / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics*; D010316:Particle Size; D010710:Phosphates / Q000737:chemistry / Q000493:pharmacokinetics; D011208:Powders / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D014961:X-Ray Diffraction
chemical_list: D008081:Liposomes; D010710:Phosphates; D011208:Powders; D053139:Oseltamivir; D008353:Mannitol; D007930:Leucine; D007785:Lactose; C535162:oseltamivir carboxylate
keywords: Inhalation powders; LC–MS; liposome; oseltamivir carboxylate; oseltamivir phosphate