Precipitates

The use of coprecipitates and complexes has, in contrast, received significant attention in recent years. This has been enabled by an increased use of spray-drying [17-19], the introduction of supercritical fluid extraction techniques [20,21] and related methods, such as spray-freeze-drying [19,22]. Together, these approaches allow investigators to generate an almost infinite variety of solid particulates. Spray-drying in particular is a versatile method of producing almost ideal particulates for inhalation in a single step [17,19,23]. In addition to solutions, suspensions and emulsions can readily be spray-dried; depending upon the components, the medium [24], and the spray-drying conditions [25,26], composite particles of unique character can be produced. A fairly recent example of extended release supported by pharmacodynamic data has been published by Ben-Jebria et al. [27], where spray-dried porous particles composed of lactose (18%), DPPC (60%), albumin (18%), and albuterol (4%) (by mass) were shown to extend the duration of action of albuterol in guinea pigs given periodic carbochol challenges. The results demonstrated that resistance to bronchocon-striction could be maintained for at least 16 hours (Fig. 1). However, the interpretation of the data emphasizes the porous characteristics of the particles and less so the composition. That is, it was thought that the clearance of the large, porous particles would be diminished relative to small, nonporous particles. Unfortunately, the study lacked a true control of nonporous particles of similar composition, and thus the relative importance of particle morphology versus particle composition has not been addressed.

The effort that leads to optimization of the particle morphology is largely one of trial and error, and there is no simple means to describe the distribution of components within individual particulates. Clearly, if the majority of an active component (API) is in the interior of a particle, then the dissolution or release characteristics are likely to differ from particles where the API is predominantly on the surface. The surface distribution of proteins and polymers within spray-dried particles has been studied using electron spectroscopy for chemical analysis that involves analyzing the energy signature of electrons scattered from surfaces while being bombarded by x-rays [11,28-31]. Conclusions can then be drawn

Time (Hours)

Figure 1 Response of guinea pig airways to periodic carbochol challenges after pretreatment with dry powder formulations containing albuterol.

Time (Hours)

Figure 1 Response of guinea pig airways to periodic carbochol challenges after pretreatment with dry powder formulations containing albuterol.

about the overall distribution by comparing the initial presprayed bulk composition with the final surface composition. Taking this one step further, it should also be possible to garner some information about the release characteristics of composite particles. For instance, if there is an excess of drug at the surface then a "burst" effect is to be expected.

Surface changes are highly relevant for inhalation powders since they are customarily composed of particulates of high surface area relative to their volume. This has great significance to their aerosolization characteristics and is an area of current interest [16,32-37]. But almost any change of surface where we are dealing with micron-sized particles will also manifest during dissolution, and it seems reasonable to state that changes in the salt types or use of precipitated complexes, whether via spray-drying, milling, or supercritical fluid processing, can be better exploited for pulmonary applications.

The emphasis within the text is upon extending the effects of drugs in the lungs, but equally, modulated drug delivery applies to poorly soluble drugs where enhanced dissolution is desirable. A good example is Elan Pharmaceutical's NanoCrystal® technology that could be used to enhance aerosol delivery of poorly water-soluble drug compounds. This technology involves the use of a proprietary milling process with which to generate submicron-particle-size distributions and thus to capitalize on increases in dissolution that occur through increasing the overall particle surface area. Alternatively, composites with surfactant agents might also be expected to dissolve and spread more rapidly than the drug alone. In fact, the surfactant lining layer may contribute to the dissolution of hydrophobic drugs presented to the lung surface, as has been seen for budesonide [38].

Coping with Asthma

Coping with Asthma

If you suffer with asthma, you will no doubt be familiar with the uncomfortable sensations as your bronchial tubes begin to narrow and your muscles around them start to tighten. A sticky mucus known as phlegm begins to produce and increase within your bronchial tubes and you begin to wheeze, cough and struggle to breathe.

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