Powder flow physics

Whereas the production flow charts of inorganic pigments appear to be simple, the actual processes can be very compHcated. Many pigments are not pure chemical compounds, but can be multiphase systems contaminated with various impurities and modifiers. Because pigments are fine powders, the physical properties are as critical to their appHcation performance as are the chemical properties. 

Table 1 lists a number of factors that may influence powder flow and compaction. The list is long and includes physical and mechanical properties as well as... 

As we just suggested, particle size and shape are important physical properties influencing powder flow and compaction. Particle size is a simple concept and yet a difficult one to quantitate. Feret s diameter, Martin s diameter, projected area diameter, specific surface diameter, Stokes diameter, and volume diameter are but several of the measurements that have been used to quantify particle size using a variety of methods. 

Powder flow is most frequently thought of as relevant to formulation development, and there are numerous references attempting to correlate any one of a number of measures of powder flow to the manufacturing properties of a formulation [34—40]. In particular, the importance of physical properties in affecting powder flow has been well documented. Research into the effect of the mechanical properties on powder flow has, however, been very limited. It is, of course, important to be able to determine and quantitate the powder flow properties of formulations. It is of equal importance, however, to determine the powder flow characteristics of bulk drug early in the development process (preformulation phase). Often, the preformulation or formulation scientist is constrained by time, materials, and manpower. Yet certainly the preformulation studies carried out should be meaningful. Well-defined experimental methods and procedures should be used the information generated should be reproducible and permit useful predictions to be made. 

G. E. Amidon, Physical and Mechanical Property Effects on Powder Flow, AAPS Symposium, November 1988. 

In situations where a complete description of the physical behavior of a system is unknown, scale-up approaches often involve the use of dimensionless groups, as described in Chapter 1. Unlike flow behavior in a blender, the flow behavior of powder through bins and hoppers can be predicted by a complete mathematical relationship. In light of this, analysis of powder flow in a bin or... 

The critical unit operations that should be monitored and/or optimized are the reaction and fermentation steps for the purpose of increasing API yield and reducing the residual impurity profile. Other critical unit operations that are especially important to the end user (pharmaceutical dosage form operations) include precipitation or crystallization, milling, sizing, and purification operations, which may affect the physical properties (particle size and shape, bulk powder flow, blend uniformity, and compressibility) of the API. 

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. 

Besides the use of excipients, powder flow and dispersion can also be improved by manipulation of the physical characteristics of the powder. 

Crowder, T.M. Hickey, A.J. The physics of powder flow applied to pharmaceutical solids. Pharm. Techno. 2000, 24 (2), 50-58. 

The measurement of particle size is a key issue in the formulation of many pharmaceutical products. Particle size distribution is known to directly influence physical properties of powders, such as dissolution rate, powder flow, bulk density, and compressibility. Conventional methods of particle size measurement include sieve analysis and laser diffractometry. ... 

Crystal habit Physical Powder flow, tabletabilily... 

Solid-state properties Physical/molecular Powder flow, tabletabilily, solubility, dissolution rate, stability... 

For pharmaceutical materials moisture is known to affect a wide range of properties such as powder flow compactibility and stability (physical chemical and microbiological) (8 46-53). The interaction between moisture and a solid is complex and can occur in a variety of ways. For example water can be stoichiometrically incorporated into a solid s crystal structure in the form of a hydrate (pseudo-hydrate) as discussed previously in this section. In addition moisture can have non-stroichiometrical i.e., nonspecific interactions with a solid by adsorbing on the surface or being absorbed into the material and acting as a plasticizer. These non-specific interactions are more common in amorphous or semi crystalline materials and are the subject of this section. 

Amidon GE. Physical test methods for powder flow characterization of pharmaceutical materials. A review of methods. Pharm Forum 1999 25 8298-8305. 

Other physical parameters of powder, such as flowability, must be observed and recorded. Does the powder flow freely Does the powder cling to the sides of the container, is the powder fluffy, or does it have the sparkle of a crystal Refer to the specification document for the physical characteristics of the sample and either confirm if the sample has those characteristics or not. It may be helpful to obtain a retain sample from a previous lot of acceptable material for comparison. 

---