title: The effects of polyvinyl alcohol on the in vitro stability and delivery of spray-dried protein particles from surfactant-free HFA 134a-based pressurised metered dose inhalers.
abstract: The objective of the present study was to investigate the physical stability of spray-dried proteins within surfactant-free hydrofluoroalkane (HFA) pressurised metered dose inhalers (pMDIs) during prolonged storage. Two model proteins (lysozyme and catalase) were spray-dried and stabilised in the presence of excipients, and subsequently suspended within HFA 134a. The pMDIs were stored valve-up for 6 months at room temperature (ca. 25 degrees C). Activities of the proteins were determined using biological assays and the fine particle fraction of the pMDIs was measured using a twin-stage impinger. The biological activities of catalase and lysozyme were found to be preserved in the presence of sugars and/or 80% hydrolysed polyvinyl alcohol (PVA) during spray drying. In addition, suspending the stabilised proteins within HFA for up to 6 months had little effect on their activity. The aerosolisation performance of lysozyme or catalase formulations containing either sucrose or trehalose as stabilisers appeared to deteriorate as a function of storage time. However, those formulations containing PVA were found to generate the greatest fine particle fraction, which in some cases was up to 50%, and to possess excellent physical stability during storage. The results indicated that the presence of PVA in the spray-dried stabilised protein particles could enhance the physical stability of particles, when suspended in the surfactant-free HFA MDI formulations, without affecting the protein stability upon prolonged storage.
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Xi Bei Wang, Hai Dian District, Beijing 100094, PR China.
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Liao
authors.forename: Marc B
authors.initials: MB
authors.lastname: Brown
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Jones
authors.forename: Tahir
authors.initials: T
authors.lastname: Nazir
authors.forename: Gary P
authors.initials: GP
authors.lastname: Martin
mesh_terms: D000335:Aerosol Propellants / Q000737:chemistry*; D002374:Catalase / Q000737:chemistry / Q000648:ultrastructure; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry*; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D036501:Metered Dose Inhalers; D008855:Microscopy, Electron, Scanning; D009113:Muramidase / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D011142:Polyvinyl Alcohol / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry* / Q000648:ultrastructure; D013499:Surface Properties; D005466:Fluorocarbons
chemical_list: D000335:Aerosol Propellants; D002374:Catalase; D005079:Excipients; D006845:Hydrocarbons, Fluorinated; D009113:Muramidase; D011142:Polyvinyl Alcohol; D011506:Proteins; C094049:apaflurane; D005466:Fluorocarbons