Particle size impaction testing

Testing. Various test methods are provided by ASTM (16). These iaclude pigment tests of importance such as chemical analysis, presence of oversize particles, oil absorption, particle size distribution, degree of dispersion, presence of soluble components, etc. Numerous tests are also given by ASTM for the properties of filled and unfilled polymers. These iaclude, for example, such properties as impact resistance, stiffness, viscosity, tear resistance, hardness, color, and electrical resistivity. 

Pendimethalin, 73 319 Pendulum impact tests, 19 580 Penetrating particle size, in depth filtration theory, 11 340-341... 

For any new excipients, APIs or drug products (where new does not necessarily mean novel, but new to the receiving site) there are additional testing criteria, e.g. supplier audits, third-party contract laboratory audits, analytical method transfers, sample management/tracking, etc. For those key excipients, where there is on-site historical experience, it still behoves both parties to check whether the local grade/supplier used by the CMO is equivalent to that used by the supplier (Worsham, 2010). There are many examples of differences in excipient physical properties, e.g. particle size, which have been attributed to different excipient sources that could ultimately impact on the performance of those excipients in formulated products (Frattini and Simioni, 1984 Dansereau and Peck, 1987 Phadke et al., 1994 Lin and Peck, 1994). 

Raman spectroscopy s sensitivity to the local molecular enviromnent means that it can be correlated to other material properties besides concentration, such as polymorph form, particle size, or polymer crystallinity. This is a powerful advantage, but it can complicate the development and interpretation of calibration models. For example, if a model is built to predict composition, it can appear to fail if the sample particle size distribution does not match what was used in the calibration set. Some models that appear to fail in the field may actually reflect a change in some aspect of the sample that was not sufficiently varied or represented in the calibration set. It is important to identify any differences between laboratory and plant conditions and perform a series of experiments to test the impact of those factors on the spectra and thus the field robustness of any models. This applies not only to physical parameters like flow rate, turbulence, particulates, temperature, crystal size and shape, and pressure, but also to the presence and concentration of minor constituents and expected contaminants. The significance of some of these parameters may be related to the volume of material probed, so factors that are significant in a microspectroscopy mode may not be when using a WAl probe or transmission mode. Regardless, the large calibration data sets required to address these variables can be burdensome. 

Mill type What mill type (e.g., impact or screen) should be used Each has several variants, depending on the means to reduce the particles. The type of mill can generate a different particle size/size distribution. Particle size testing will need to be conducted and the results examined when substituting mill types. 

In essence, the test battery should include XRPD to characterize crystallinity of excipients, moisture analysis to confirm crystallinity and hydration state of excipients, bulk density to ensure reproducibility in the blending process, and particle size distribution to ensure consistent mixing and compaction of powder blends. Often three-point PSD limits are needed for excipients. Also, morphic forms of excipients should be clearly specified and controlled as changes may impact powder flow and compactibility of blends. XRPD, DSC, SEM, and FTIR spectroscopy techniques may often be applied to characterize and control polymorphic and hydrate composition critical to the function of the excipients. Additionally, moisture sorption studies, Raman mapping, surface area analysis, particle size analysis, and KF analysis may show whether excipients possess the desired polymorphic state and whether significant amounts of amorphous components are present. Together, these studies will ensure lotto-lot consistency in the physical properties that assure flow, compaction, minimal segregation, and compunction ability of excipients used in low-dose formulations. 

The characterization and quality control of the particle size distribution of the discharged aerosol has become one of the key tests applied to MDI and other inhaler products, and a wide variety of methods have been developed to make this possible. The available methods can be broadly split into two categories optical (typically laser) methods or methods based on inertial impaction. 

Aerosols present a special case in that the investigator needs to measure the mass concentration of the chemical, the chemical composition as a function of particulate size, and the particle-size distribution of the aerosol. No continuous sampling instruments are available to measure both particle-size and chemical concentration. Particle detection can be accomplished using both forward- and back-scatter detectors. A typical back-scatter allows for non-invasive determinations over a range from 6 to 10 000 mg m . In the test, the aerosol is drawn through an orifice and articles impact on a surface positioned between a source and a counter. 

Pentamidine can cause bronchospasm and airway irritation in humans [9]. This appears to be caused by the pentamidine moiety itself, because similar irritation is seen in nonisethionate salts of pentamidine. Because P. carinii habitats the alveolus and because of the potential adverse effects of pentamidine on the airways, pentamidine ideally should be aerosolized in a small particle, between 1 and 2 pm. Studies that make in vitro comparisons of nebulizers cannot be valid unless the particle sizes are identical. The present state of knowledge cannot allow determination of the most effective device because not all the devices have been comparatively tested in humans [10,11]. The optimal particle size for alveolar deposition is between 1 and 3 pm, with 1 pm achieving more peripheral distribution and less airway distribution [12-14]. However, 19% of particles as small as 2 pm still impact in the tracheobronchial regions. The ideal device should have a particle size of 1 -2 pm with a high output. Particles between 0.5 and 1 pm have relatively less alveolar deposition than particles between 1 and 2 pm. Other features, such as reservoirs, flows, and external filters, may also be important [9]. However, any nebulizer with particle sizes, on average, greater than 8 pm would not deliver adequate dmg to the alveoli. 

---