Suspensions nebulisation

Instruments that have burners and require nebulisation of dilute aqueous sample solutions generally have low background noise in the signal. With graphite furnaces, incomplete atomisation of the solid sample at elevated temperatures can produce interfering absorptions. This matrix effect does not exist in an isolated state and thus cannot be eliminated by comparison with a reference beam. This is notably the case for solutions containing particles in suspension, ions that cannot be readily reduced and organic molecules, all of which create a constant absorbance in the interval covered by the monochromator. 

Crude inhalers have been used for medicinal purposes for at least two centuries. Solutions of volatile aromatic substances with a mild irritant action, inhaled as vapour arising from hot aqueous solutions, have been used for many years. Particles from the older nebulisers would settle without reaching the patient s face (a 100 m particle of unit density settles in still air at a velocity of 8 cm s ). The duration of existence of a suspension of particles of size around 10 m is so brief that the upper limit of aerosols of therapeutic interest is well below this size. Special devices are required to generate these. 

Suspensions and particles must be <4 pm to avoid blocking the nebuliser. 

Samples for trace metal analysis by A AS or ICP-OES must be presented to these instruments in liquid form. However, in some cases, samples are submitted as powders or solids (chippings, residues, etc.) requiring chemical decomposition prior to metal analysis that can lead to systematic errors in accuracy and precision of measurements. There have been many attempts to introduce samples as a slurry suspension and these were found to be successful for a limited number of samples provided that the particle sizes are suitably small. In most cases the nebulisation of the majority of samples analysed this way has shown that very low sample-introduction efficiency caused by variable particle sizes is in some cases difficult to dissociate, owing to the short residence times in the plasma. The availability of standards for this type of analysis is non-existent or difficult to obtain. 

Precipitation from a concentrated solution of cations can be performed by solvent evaporation. To ensure that the particle size remains small, the concentrated solution may be atomised at high pressure into fine droplets of 100-500 pm diameter the solvent is rapidly evaporated by an upward stream of hot gas. The particles obtained, which can be as small as 100 nm, are compacted and calcined to produce the ceramic. A schematic representation of the spray-drying process is shown in Fig. 3.4. Several alternative methods are currently under development they are known as aerosol synthesis, aerosol pyrolysis or mist pyrolysis, depending on the specific technique to produce the gaseous suspension of fine particles aerosols are produced in high pressure nozzles and mists are obtained by means of nebulisers. YIG particles (0.25 pm) have been obtained by mist pyrolysis (Matsumoto et ai, 1991) by nebulising an aqueous solution of... 

B) liquid preparations for nebulisation and (C) pressurised metered-dose preparations for inhalation. They are added to hot water to obtain inhalable vapours or converted into aerosols by continuously operating nebulisers or metered-dose nebulisers, and they can be solutions, suspensions or emulsions. They may be prepared by dilution of concentrated preparations or by dissolution of powders. The pH of liquid preparations for use in continuously operating nebulisers has to be within the range between 3 and 8.5. Suspensions or emulsions have to be readily dispersible on shaking and remain sufficiently stable to enable the correct dose to be delivered. 

Currently, suspensions prepared from micronised active substances are the only marketed dehvery system for nebulisation of poorly water soluble substances such as steroids and cyclosporine [53]. Several problems are inherent in nebulising micro-suspensions and they vary from non-optimised lung deposition for the active substance to heterodispersity of the active substance concentration in the aerosol droplets and poor compatibility with different types of nebulisers, particularly ultrasonic devices. Suspensions may also have poor stability and the two components (solid and liquid) tend to separate with time within the formulation by sedimentation or flocculation, depending on the particle density relative to that of the liquid. Several jet nebulisers can deliver suspensions quite effectively, even independently of the primary particle size [54], but ultrasonic devices may convert primarily the continuous phase into aerosol whereas vibrating mesh inhalers can be blocked by particles being larger than the pore diameter of the membrane. 

In addition to solutions and suspensions, liposomal formulations of active substances are used and various nanoemulsion-based formulations and micellar solutions are explored for nebulisation [55]. Currently, no marketed inhaled liposomal products are available... 

Najlah M, Parveen I, Alhnan MA, Ahmed W, Faheem A, Phoenix DA, Taylor KM, Elhissi A (2014) The effects of suspension particle size on the performance of air-jet, ultrasonic and vibrating mesh nebulisers. Int J Pharm 461(l-2) 234—241... 

Most corticosteroids nasal sprays (licensed preparations) are suspensions in which croscarmellose sodium is used as viscosity enhancer. The inhalation liquids for nebulisation with the same type of active substances however only contain polysorbate and sorbitan laureate to stabilise the suspension. For atomisation in jet nebulisers, the liquid should not be too viscous, in order to prevent clogging of the nebuliser. 

The European Pharmacopeia lists four different devices to enable administration to the lungs, namely nebulisers, pressurised metered dose inhalers (pMDls), non-pressurised metered-dose inhalers (MDls) and dry powder inhalers (DPls) [7]. Aerosolisation is based on nebulisation or atomisation for the three devices using aqueous solutions or suspensions and dedicated to dry powder dispersion for DPls as addressed in this project [1, 7]. 

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