Delivery of propellant soluble drug from a metered dose inhaler.

Abstract

hexamethylpropyleneamine oxime size of the delivery orifice (0-46, 0 61, and prepared by the addition of 5 GBq 9'Tc-0-76 mm internal diameters) and the sodium pertechnetate in 5 ml saline to a phial effect of attaching a spacer were assessed. containing a freeze dried mixture of 0 5 mg Lung deposition was independent of the hexamethylpropyleneamine oxime, 7-6 pg orifice size within the actuator. Without stannous chloride dihydrate, and 4-5 mg the spacer the average dose deposited in sodium chloride (Amersham International, the lungs was 39%, with 15% penetrating Amersham). The freshly prepared 99"Tcinto the peripheral part of the lungs. hexamethylpropyleneamine oxime was added Attachment of the spacer to the mouth-to a separating funnel containing 2 ml tripiece increased the mean lung deposition chlorofluoromethane. After the mixture had to 57% and reduced oropharyngeal been shaken for two minutes the organic layer deposition. The Metered dose inhalers should be actuated during slow inhalation, followed by breath holding for 10 seconds, for maximum drug deposition in the lungs. For drug particles suspended in the propellant, up to 15% of the dose can be' deposited in the lungs with this technique.' Many patients, however, fail to achieve deposition of even 10%.2 Deposition can be improved by the attachment of a spacer to the actuator mouthpiece,' the spacer providing a reservoir for the aerosol and reducing the need for precise synchronisation between actuation and inhalation. In addition, large aerosol particles tend to--deposit in the spacer and reduce the amount of drug becoming impacted in the oropharynx. ' The deposition of particulate suspensions nitrogen, was added 0-3 ml radiolabelled trichlorofluoromethane and 10 ml propellant mixture from a precooled canister. After a metering valve had been fitted the canister was allowed to warm to room temperature and the contents were assayed for radioactivity. Typically, 2-3 MBq 99"Tc labelled propellant was delivered per actuation. Aerosol delivery was compared by using actuators with internal orifice diameters of0-46, 0-61, and 076 mm. Aerosol deposition from the actuator with the 0-61 mm diameter orifice was also compafed with and without the addition of a 10 cm long, 45 cm' prototype commercial spacer (without a valve) to the mouthpiece. The dose distributions from each delivery system were assessed by using an Andersen eight stage sampler. Ten doses of radiolabelled propellant were fired into the sampler at a rate of one dose every 15 seconds. The apparatus was then dismantled and each component, including the actuator, was assayed for radioactivity with a probe scintillation detector.Aerosol doses were administered to six healthy subjects aged 18-25 years. All were 245 on 10 May 2018 by guest. Protected by copyright.

Efficient Delivery to the Lungs of Flunisolide Aerosol From a New Portable Hand-Held Multidose Nebulizer

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