title: Formulation and evaluation of novel reverse microemulsions containing salmon calcitonin in hydrofluoroalkane propellants.
abstract: To develop reverse microemulsion as a potential strategy for pulmonary delivery of salmon calcitonin (sCT) in HFA134a propellant of pressurized metered dose inhalers (pMDIs), pluronic P85 (P85) was chosen as the most appropriate surfactant to form microemulsions containing sCT. Formulation parameters, including the surfactant and ethanol content, water content, and sCT loading, were optimized to obtain two desired pMDI formulations A and B with clear and transparent appearance, Tyndall effect, good physical stability and aerosolization properties. Aerosolization properties of the optimized pMDIs were assessed by next generation impactor (NGI) and twin-stage impactor (TSI), and the dose of sCT in each stage was assayed by HPLC. The fine particle fraction (FPF) of formulations A and B were both at the range of approximately 28.0-36.0%. Cytotoxicity studies indicated the cell viability determined by MTT assay only slightly dropped when the A549 cells were exposed to the pMDI formulations. Pharmacological study performed on the male Wistar rats showed the intratracheal administration of the microemulsion pMDIs containing sCT exhibited similar but prolonged hypocalcemic activity compared with the intravenous injection of sCT solution. Therefore, such reverse microemulsions are potential for pulmonary delivery of therapeutic peptides using HFA-pMDIs.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China; Research and Development Center of Pharmaceutical Engineering, Sun Yat-sen University, Guangzhou, China.
authors.forename: Ziyun
authors.initials: Z
authors.lastname: Shan
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yinhe
authors.initials: Y
authors.lastname: Tan
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Lingzhen
authors.initials: L
authors.lastname: Qin
authors.affiliation: Guangzhou Neworld Pharmaceutical Ltd. Co., Guangzhou, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Pan
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhouhua
authors.initials: Z
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiu
authors.initials: X
authors.lastname: Yu
authors.affiliation: Faculty of Automation, Guangdong University of Technology, Guangzhou, China.
authors.forename: Qinruo
authors.initials: Q
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China; Research and Development Center of Pharmaceutical Engineering, Sun Yat-sen University, Guangzhou, China. Electronic address: chuanbin_wu@126.com.
authors.forename: Chuanbin
authors.initials: C
authors.lastname: Wu
mesh_terms: D000335:Aerosol Propellants / Q000008:administration & dosage* / Q000737:chemistry*; D000336:Aerosols; D000818:Animals; D002116:Calcitonin / Q000008:administration & dosage / Q000737:chemistry*; D002118:Calcium / Q000097:blood; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004655:Emulsions; D000431:Ethanol / Q000737:chemistry; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000008:administration & dosage* / Q000737:chemistry*; D008297:Male; D020442:Poloxamer / Q000737:chemistry; D017208:Rats, Wistar; D013501:Surface-Active Agents / Q000737:chemistry; D005466:Fluorocarbons
chemical_list: D000335:Aerosol Propellants; D000336:Aerosols; D002116:Calcitonin; D002118:Calcium; D004655:Emulsions; D000431:Ethanol; D006845:Hydrocarbons, Fluorinated; D020442:Poloxamer; D013501:Surface-Active Agents; C028815:salmon calcitonin; C094049:apaflurane; D005466:Fluorocarbons
keywords: Aerosolization; Fine particle fraction; Hypocalcemia activity; Pressurized metered dose inhaler; Reverse microemulsion; Salmon calcitonin