Particle production with nebulizers

Specific advancements ia the chemical synthesis of coUoidal materials are noteworthy. Many types of genera ting devices have been used to produce coUoidal Hquid aerosols (qv) and emulsions (qv) (39—43) among them are atomizers and nebulizers of various designs (30,44—50). A unique feature of produciag Hquid or soHd coUoids via aerosol processes (Table 3) is that material with a relatively narrow size distribution can be routinely prepared. These monosized coUoids are often produced by relying on an electrostatic classifier to select desired particle sizes ia the final stage of aerosol production. 

Blow-fill technology is an aseptic process whereby the container is formed from thermoplastic granules, filled with sterile solution and sealed, all within one automatic operation. The bulk solution should have a low bioburden and is delivered to the machine through a filling system that has been previously sanitized and steam sterilized in situ. Concern has been expressed that the machine itself may generate particles. The plastic granules are composed usually of polyethylene, polypropylene or one of their copolymers and are heat extruded at 200°C into a tube. The two halves of a mould close around this tube and seal the base. The required quantity of sterile fluid is filled into the container, which is then sealed. Products packed in this way include intravenous solutions, and small volume parenteral, ophthalmic and nebulizer solutions. The... 

The performance of pMDIs and DPIs is scrutinized in terms of efficiency and reproducibility of dose delivery, particle size, and distribution under a range of storage conditions, with respect to temperature and humidity, for extended periods of time (up to 2 years).50 Since nebulizer products do not bring the device in contact with the drug until the point of use, a slightly different approach is taken to their approval. Recommended devices and conditions of operation for the delivery of a particular drug must now be stated. The solution formulation is then viewed as a sterile parenteral product and requires concomitant testing. 

To measure an atomic absorption signal, the analyte must be converted from dissolved ions in aqueous solution to reduced gas-phase free atoms. The overall process is outlined in Figure 6.16. As described earlier, the sample solution, containing the analyte as dissolved ions, is aspirated through the nebulizer. The solution is converted into a line mist or aerosol, with the analyte still dissolved as ions. When the aerosol droplets enter the flame, the solvent (water, in this case) is evaporated. We say that the sample is desolvated. The sample is now in the form of tiny solid particles. The heat of the flame can melt (liquefy) the particles and then vaporize the particles. Finally, the heat from the flame (and the combustion chemistry in the flame) must break the bonds between the analyte metal and its anion, and produce free M° atoms. This entire process must occur very rapidly, before the analyte is carried out of the observation zone of the flame. After free atoms are formed, several things can happen. The free atoms can absorb the incident radiation this is the process we want. The free atoms can be rapidly oxidized in the hostile chemical environment of the hot flame, making them unable to absorb the resonance lines from the lamp. They can be excited (thermally or by collision) or ionized, making them unable to absorb the resonance lines from the lamp. The analyst must control the flame conditions, flow rates, and chemistry to maximize production of free atoms and minimize oxide formation, ionization, and other unwanted reactions. While complete... 

Ultrasonic nebulization has two advantages over pneumatic nebulization. The aerosol particles have a lower diameter and a narrower particle size distribution compared with pneumatic nebulization (< 5 compared with 10-25 pm). Therefore, aerosol production efficiency may be up to 30%, and analyte introduction efficiency is high. No gas flow is required for aerosol production, the trans-... 

Another type of atomization employed for pharmaceuticals is supercritical fluid nebulization. The process uses carbon dioxide as an aerosolization aid, which permits drying at lower temperatures than is usually needed in conventional spray drying (55). Within the atomization system, supercritical carbon dioxide is intimately mixed with aqueous solutions containing API, often proteins or peptides. The outcome is the formation of microbubbles, which are rapidly dried in <5 sec, resulting in dried particles predominately <3 pm in diameter (56,57). This method is generally applied for the production of materials for pulmonary use or to achieve increased bioavailability (58). 

A compromise between the concentration of the precursor solution, the flow rate of air fed to the nebulizer, and the orifice of the nebulizer needs to be met in order to obtain crystalline materials with nanometric particle size. A further optimization parameter is the humidity degree of the air fed to the nebulizer, which needs also to be controlled as it ensures a constant precursor concentration during nebulization thus providing constant production rate and particle size [71],... 

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