Excipient bulk density

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. 

Lot-to-lot differences in the purity of the therapeutic agent must be considered when evaluating in-process and finished-product test results. In addition to potency such qualities as particle size distribution, bulk density, and source of the material will be of interest. Such information should be available from the raw material test reports prepared by the quality control laboratory for each lot of material received. The physical characteristics of the excipients should not be overlooked, especially for those materials with inherent variability. Metallic stearates is a classic example. In such instances, the source of supply is desirable information to have available. 

True and bulk density An excipient (e.g., diluent) that has a similar bulk density as the drug may be selected to minimize segregation, especially with a direct compression formulation. 

In solid dosage forms, granulation is frequently used to improve excipient properties such as flowability, compactibility, bulk density, granule strength, dissolution rates, and so The granulation process... 

Bulk powder properties are extremely important in pharmaceutical processing. Knowledge of the true and bulk densities of the drug substance as well as of the excipients is extremely useful in... 

The powder s flow properties are also important because they control the physical processes that are used to manipulate the material. Carrs s index, which is a measure of powder bulk density and angle of repose, provides information on flow properties, which are important when production utilises high-speed tableting machines. Compression properties are important in determining the ability of the compound to form tablets wdth or without the presence of excipients. 

Excipients could usefully be classified or tested according to their properties at three levels, viz. molecular, particulate, and bulk properties. Those are tested for by the manufacturer of a dosage form. It is not clear which of those properties should be covered by the official compendia. Testing of functionality, i.e., at particulate or bulk level, does not seem to be possible yet. Typical tests are bulk density, specific surface area, flowability, and particle size distribution. However, the standardization of methodology in compendia, without specification limits, will probably be of help for both vendor and buyer. Therefore, functionality related tests are now being proposed in the pharmacopoeias. As excipients are getting more complex, their analytical characterization is very important. Interesting opportunities lie ahead, particularly with macromolecular separation, MALDI-TOF-MS, and spectrometric methods such as NIR. 

Ph. Eur. contains a monograph on FRCs. The chapter is not mandatory, neither is the FRC-section in specific monographs. But that does not mean that FRCs are unimportant. Especially in pharmaceutical development FRCs determine the design space of a medicinal product. Many excipients are manufactured by industries other than the pharmaceutical industry, so in many cases the excipient manufacturer has little knowledge about the pharmaceutical use of an excipient. Several methods to determine FRCs are described in Ph. Eur. e.g. Particle-size determinatimi. Specific surface area by gas adsorption. Powder flow. Bulk density and tapped density. Wettability of porous solids including powders. 

Bulk density -Type and amount of additional excipients... 

The effect of various excipients on the flow of paracetamol was evaluated using (i) conditioned bulk density (CBD), (ii) compressibility and (iii) aeration energy programs of the FT4 (Figure 1.11). 

Bulk powder properties are important in understanding the handling properties of an excipient or a granulated product. Common parameters measured are bulk and tap density. From these values the compressibility can be calculated using the following ... 

Powders are porous materials and their bulk and relative densities can change with consolidation (6). However, a powder s true density is the density of its solid phase only and thus is independent of the state of consolidation. The true density of organic excipients typically ranges from 1.0 to 1.6g/cm3 while inorganic excipients (e.g., calcium phosphate) show values greater than 2g/cm3. True density is used to determine powder or compact solid fraction (SF) (see below) and it may be a consideration when selecting excipients if segregation is a concern. True density is often determined by gas pycnometry. 

---