Crystalline powder flow properties

Anhydrous lactose is a free-flowing crystalline /3-lactose without water of hydration, first described in the literature in 1966.33 It is available in a white crystalline powder that has good flowability and high compactibility. Anhydrous lactose can be reworked or milled, resulting in a smaller loss of compactibility than with other forms of lactose (due to its high fragmentation propensity). Table 7.4 lists the physical properties of the product. The product is very suitable for moisture-sensitive chug formulations. 

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 term crystallization describes the production of a solid, single-component, crystalline phase from a multicomponent fluid phase. The importance of crystallization lies primarily in the purification achieved during the process and in the physical properties of the product. A crystalline powder is easily handled, stable, and often possesses good flow properties and an attractive appearance. 

Powdered cellulose has acceptable compression properties, although its flow properties are poor. However, low-crystallinity powdered cellulose has exhibited properties that are different from standard powdered cellulose materials, and has shown potential as a direct-compression excipient. ... 

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. 

Properties Free-flowing, white, crystalline powder no odor. Mp 244C. Partially soluble in benzene and methylene chloride insoluble in water. Permissible in contact with food products. Combustible. 

Properties Orange-colored, free-flowing, crystalline powder. 

Kulicke WM, Kull AH, Kull W, Thielkmg H, EngeUiart J, Pannek JB (1996) Characterization of aqueous carboxymethylcellulose solutions in terms of their molecular structure and its influence on rheological behavior. Polymer 37(13) 2723-2731 Kulicke WM, Reinhardt Fuller UGG, Arendt O (1999) Characterization of the flow properties of sodium carboxymethylcellulose via mechanical and optical techniques. Rheol Acta 38 26-33 Kulshreshtha AK, Dweltz NE (1973) Para crystalline lattice disorder in cellulose - 1. Reappraisal of the application of the two-phase hypothesis to the analysis of powder x-ray diffractograms of native and hydrolyzed cellulosic materials. J Polym Sci 11 487 97 Mathur NK, Mathur V (2001) Chemical Weekly, July Edition, 155... 

A critical aspect of this type of research is the designing of appropriate reaction cells. To correlate the structure and activity of the catalysts, the flow properties in the EXAFS should ideally be similar to those found in the reactor and for time resolved studies, diffusion (film and pore diffusion) should be faster than the corresponding chemical reaction. Thus several different designs have been reported. Perhaps the three most popular methods are the pelletized catalyst powder disk mounted in a gas cell mounted powder and plug-flow capillary reactor (18,149,162). At this stage, we also draw the attention of the reader to the specially designed hydrothermal vessels that have been used for studying the self-assembly processes for crystalline materials with XAS (163-165). 

Cellulose is beta-glucosidic polymerised glucose with a polymerisation degree of approximately 3000, see Fig. 23.2. Microcrystalline cellulose is crystalline, partially depolymerised cellulose. It is available in different qualities with particle sizes ranging between 20 and 200 pm. The most suitable quality for the production of tablets, capsules and powders has an average particle size of 100 pm and is available under various brand names including Pharmacel 102 and Avicel PH 102 . It is a chemically inert substance, has reasonably favourable flow properties and is almost insoluble. The particle size of 100 pm corresponds to that... 

The physical properties of the solid state seen in crystals and powders of both drugs and pharmaceutical excipients are of interest because they can affect both the production of dosage forms and the performance of the finished product. Powders, as Pilpel reminded us, can float like a gas or flow like a liquid but when compressed can support a weight. Fine powders dispersed as suspensions in liquids are used in injections and aerosol formulations. Both liquid and dry powder aerosols are available and are discussed in Chapter 9 some properties of compacted solids are dealt with in Chapter 6. In this chapter we deal with the form and particle size of crystalline and amorphous drugs and the effect these characteristics have on drug behaviour, especially on drug dissolution and bioavailability. 

The enhanced physical properties for supercritically produced salme-terol (e.g., high crystallinity, polymorphic purity, powder uniformity) correlate well with the enhanced dispersion and flow behavior of this powder. However, as shown in some other investigations (12,28), particle size and shape, surface energy, and crystallinity may have to be optimized separately, using all process parameters available, perhaps including a coformulation step. For some compounds with low solubility in water, a compromise must be found between improved bioavailability and physicochemical stability. 

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