Immunoglobulin G particles manufacturing by spray drying process for pressurised metered dose inhaler formulations.

OBJECTIVE: The objective of this work is to show the feasibility of manufacturing from a spray drying process particles containing immunoglobulin G capable of being administered by inhalation via a pressurized metered dose inhaler. METHODS: Spray drying were made from aqueous solutions containing IgG and two types of excipients, mannitol and trehalose, with two ratios: 25% w/w and 75%w/w. The physicochemical and aerodynamic properties of the powders obtained were characterized just after manufacturing and after 1 month of storage at 40°C/75% RH according to criteria defined as needed to satisfy an inhaled formulation with a pressurized metered dose inhaler. Maintain of the biological activity and the structure of IgG after atomization was also tested by slot blot and circular dichroism. RESULTS: All spray-dried powders presented a median diameter lower than 5µm. The powders atomized with trehalose showed a solid state more stable than those atomized with mannitol. All atomized powders were in the form of wrinkled particles regardless the nature and the ratios of excipients. The results showed that the aerosolisation properties were compliant with the target, independently of the excipient used at a ratio of 25% w/w IgG-excipient. Moreover, the addition of excipient during the atomization process the denaturation of IgG was limited. CONCLUSION: This study showed that the use of trehalose as excipient could satisfy the requirements of an inhaled formulation with a pressurized metered dose inhaler.

Development and performance of a new hydrofluoroalkane (HFA 134a)-based metered dose inhaler (MDI) of salmeterol.

In response to the Montreal Protocol, a salmeterol (Serevent) metered dose inhaler (MDI) has been developed containing the non-chlorofluorocarbon propellant, hydrofluoroalkane 134a (HFA), to replace the marketed Serevent chlorofluorocarbon (CFC) propellant MDI. This paper details the pharmaceutical assessment of salmeterol HFA MDI and confirms that this product meets the current Committee for Proprietary Medicinal Products regulatory requirements, and is comparable to the CFC MDI in product performance. Criteria investigated included fine particle mass (FPM), dose delivery and uniformity, priming requirements and simulated-use-testing. Dose delivery was unaffected by changing product orientation during storage. The mean dose delivered per actuation ranged from 21.3 to 22.4 microg, and all individual doses were within the +/-25% defined limits of the target ex-actuator dose of 21 microg. The FPM results, defined as the mass of particles between 1.1 and 4.7 microm in diameter (the sum of the mass deposited on stages 3-5 of the Andersen Cascade Impactor), were similar for the HFA and CFC products. The mean FPM values of the two HFA clinical batches were 8.7 and 10.1 microg, covering the values obtained during the development, and the one of the CFC clinical batch was 10.0 microg. Comparability in aerosol characteristics was also demonstrated when the salmeterol HFA inhaler was tested using a large volume spacer (Volumatic).