Use of Spacers

A number of recommendations can be made for the optimal use of spacers. Slow inhalation is preferable since the impaction of particles is proportional to velocity and particle size. A slow flow reduces the risk of impaction on valves and anatomic structures such as the pharynx or vocal cords. In addition, high flow rates enhance central airway deposition caused by inertial impaction and therefore reduce deposition in peripheral airways. 

It is essential that a pMDI is shaken before every use (see Chap. 10), since failure to do this will dramatically reduce drug delivery (60,61). The spacer should be positioned before actuating the pMDI because the fallout of aerosol reduces the available dose over time. Movement of the spacer should be avoided, as this will reduce the drug available for inhalation due to impaction on the sides of the spacer wall (62). 

If multiple doses are prescribed, they should be given separately, since simultaneous administration causes a significant rednction in the recovered dose (44,63,64). This may be less of a concern with nonelectrostatic spacers. 

The number of breaths required to empty a spacer obviously depends on the size of the patient and the spacer. The aerosol empties from a spacer in an exponential manner, since inhaled aerosol is replaced by air thns dilating the remaining aerosol. Adults may empty a spacer in one to two inhalations, whereas in laboratory studies in which ventilators were nsed to mimick the breathing of toddlers, commonly used spacers for young children were emptied in two to four breaths (25). A safe recommendation wonld be to snggest 10 breaths in infants, 5 breaths in toddlers and 2 slow deep inhalations in older children and adnlts. 

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The attractive force (F) is dependent on the Hamaker constant and the shortest distance between the particles, z. F may be decreased by decreasing A or increasing z. Theoretically, the Hamaker constant can be decreased by decreasing the densities of the two interacting particles. Since the separation distance plays a significant role in van der Waals attraction, any means to increase this distance will reduce the attractive force and increase the ease of dispersion. Surface roughening and the use of spacer particulates can increase interparticulate separation with the improved particle dispersion. 

G) Gap Test. The purpose of this test is to det the satisfactoriness of a fuze expl train when maximum gaps between expl components, which are permitted by design, are employed. The max gaps a re usua lly achieved by the selection or the modification of fuze parts or possibly by the use of spacers that will give the gaps desired. 

Traditionally, pulmonary deposition of MDIs has been in the range of 10-20% [38-40], An increase in pulmonary deposition efficiency of MDIs has been achieved with the use of spacer devices [41-46], Aerosol deposition in the human lung has also been optimized after administration from a microprocessor-controlled pressurized MDI [47, 48], Improvement of pulmonary deposition of up to 40%... 

Sealed and semi-permanent cells are most common, but variable pathlength cells are also available. A simple version of a liquid sample cell is the demountable Nujol cell which is suitable for qualitative examination of pastes or viscous liquids. The use of spacers in these devices may or may not be necessary, depending on the viscosity of the sample under investigation. NaCl, KBr, Csl, and polyethylene window materials are convenient if the sample does not contain water. A drop of liquid or paste is placed on one of the windows, and the two windows are clamped with front and back metal plates. Semi-permanent cells are suitable for quantitative work and can be cleaned easily after use (Fig. 5.2.1). 

To facilitate easy detection and improved separation, spacer components have been inserted between the members of the displacement train. The so-called Test Substance II (Camag, Muttenz, Switzerland) has numerous coloured components e.g., the Sudan Black components are members of the displacement train optimised for the ecdysteroids, semisynthetic morphine derivatives, and various phenylalkylamines. The various Sudan Black components were inserted between the components to be separated, if both the component and the ecdysteroids (or morphine derivatives or phenylalkylamines) were displaced. Black lines and white spots were observed, showing sharp separation and easy observation. In the case of the study of metabolism, the use of spacers facilitated the differentiation of poorly separated metabolites. 

There is a place for both of these devices. The deposition efficiency of both can be better than found in early studies of MDIs. Proper use of spacers improves the efficiency of MDIs, and proper inhalation flow is important for both devices. Comparative studies are legion [49,58 -65], and sorting the confusing mass of information is difficult. 

Emphasizing the importance of proper drug use and correct use of spacers and inhalers for long-term control... 

In fact, for the separation of proteins, a more pragmatic view is taken and the operating conditions are usually optimized by experiment. Such factors as type, pH, and concentration of electrolytes, capillary length, temperature, column coupling, current, and use of spacers must all be considered. 

The spacer is located between the resin carrier and the linker and, when present, should reduce factors such as steric hindrance of reactions brought about by the bulk of the resin or to modify features such as the hydrophilicity/hydrophobicity of the local environment and promote one or more of the reaction steps. Following cleavage of the final product, the spacer remains attached to the resin carrier. The use of spacers is optional they are not always necessary, but may often be advantageous. 

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