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 - Excipients

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
21 September 2005
Yong-Hong Liao, Marc B. Brown, Stuart A. Jones, Tahir Nazir and Gary P. Martin
International Journal of Pharmaceutics
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 ?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.
Keywords: Spray-drying; Protein stability; Metered dose inhaler; Pulmonary delivery; Catalase; Polyvinyl alcohol; Lysozyme; Hydrofluoroalkane
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