Excipient flowability

Because particle size is so intimately intertwined with powder performance, it is one of the prime considerations in selecting excipients to develop or improve a formulation. This is particularly important with direct compression formulations where excipient flowability and compaction performance are critical. Typically, excipients for these applications exhibit narrow size distributions with moderate-to-coarse particle size, having a mean size from 100 to 200 pm. 

When manufacturing a tablet formulation by direct compression, the particle size and size distribution of excipients have a significant impact on blending homogeneity, powder segregation, and flowability. This can result in unacceptable content uniformity and high tablet weight variation. In such situations, control of excipients can be critical to product quality. 

The presence of amorphous lactose in the excipient may have a negative effect on compactibility and product stability. Direct compression grades of lactose monohydrate are available as granulated/agglomerated particles from multiple vendors. These physical properties are listed in Table 7.4. Commercial products combine the good flowability of coarse lactose crystals and the good compressibility... 

Microcrystalline cellulose is the most compressible of any direct compression excipient. Producing a tablet of a given hardness requires less compression force for other materials. Therefore, it is usually mixed with another filler to achieve ideal compactibility and flowability of a direct compression formulation. Large particle size grades of microcrystalline cellulose are made by spray-dried processes to form dry and porous particle surfaces. The porous surfaces provide adsorption sites needed for fine dmg particles in low-dose formulations. However, microcrystalline cellulose contains trace amounts of peroxides that may lead to chemical incompatibility with oxidatively sensitive dmg substances.34... 

Fujicalin is an anhydrous dibasic calcium phosphate designed as a direct compression excipient. It has improved flowability and compaction characteristics compared with the conventional product, and maintains the ability to rapidly disintegrate.50 Fujicalin s patented manufacturing process yields porous spheres with a... 

For a two-level factorial design, only two excipients can be selected for each factor. However, for the filler-binder, a combination of brittle and plastic materials is preferred for optimum compaction properties. Therefore, different combinations such as lactose with MCC or mannitol with starch can count as a single factor. Experimental responses can be powder blend flowability, compactibility, blend uniformity, uniformity of dose unit, dissolution, disintegration, and stability under stressed storage conditions. The major advantage of using a DOE to screen prototype formulations is that it allows evaluation of all potential factors simultaneously, systematically, and efficiently. It helps the scientist understand the effect of each formulation factor on each response, as well as potential interaction between factors. It also helps the scientist identify the critical factors based on statistical analysis. DOE results can define a prototype formulation that will meet the predefined requirements for product performance stability and manufacturing. 

Powders intended for nasal administration have to be optimized in terms of particle size and morphology as these properties are related to potential irritation in the nasal cavity [23], Certain procedures (e.g., spray drying process) can modify the particle size of the drug powder raw material, but in order to optimize the morphology and flowability properties of some pure drug powders, excipients need to be used. Sacchetti et al. [28] reported that the use of mannitol as a filler and hydroxy-propylmethyl cellulose (HPMC) as a shaper of spray-dried caffeine microparticles modified the typical needle shape of spray-dried caffeine to a more convenient roundish shape. Further addition of polyethylene glycol (PEG) resulted in increased... 

Most drug and inactive excipients used in tablet formulation are in the solid state as amorphous powder or crystals of various morphological structures. There may be substantial differences in particle size, surface area, crystal morphology, wetting, and flowability as well as many physical properties of drug, excipients, and their blends [16]. Table 12 describes common micromeritic topics important to pharmaceutical preformulation. 

In order to formulate the optimal tablet, various properties should be considered, including drug-excipient compatibility, flowability, lubricity, appearance, dissolution, and disintegration [2], The prepared tablet must also meet physical specification and... 

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... 

The excipients used are fillers, but the most important are lubricants, such as magnesium stearate, PEG 6000, calcium stearate, glycerol palmito stearate, and calcium behenate, which increase the flowability but at the same time modify the hydrophobic characteristics of powders. Their choice depends on compatibility with active ingredient and the flow properties of powders. The characteristics of the excipient have been described previously. 

Bulk powder characteristics are important in understanding the handling properties of an excipient or a granulated product. A classification system to evaluate the flow properties of powders has been introduced by Carr.P A flowable powder is defined as free-flowing and tends to flow steadily and consistently, whereas a floodable powder exhibits an unstable, discontinuous, and gushing type of flow. A number of studies have investigated the bulk powder properties of starch " and granulations made with starch. The starch materials were found to exhibit poor to borderline flow properties. 

Understanding the physical properties of the raw ingredients (API, excipients) and how they affect the flowability of the final blend is crucial in selecting and designing equipment that reliably handles the final blend. Therefore, the preblending process steps and equipment parameters are often critical to the flowability of the final blend. There are several common preblending process. steps that may affect the final blendes flowability, including ... 

The excellent flowability and compressibility of spray-dried PVAc/Povidone makes this excipient particulary suitable for the manufacture of sustained-release tablets obtained by direct compression [647-649]. 

Polyvinyl acetate is described in the literature as a matrix former in theophylline sustained-release tablets obtained by hot-melt extrusion [646]. In a similar way spray-dried PVAc/Povidone can be applied for the production of tablets and pellets using its excellent flowability. In this case the pulverization of polyvinyl acetate by cryogenic grinding can be avoided and the mixture of the active ingredient with the excipients are applied directly to the melt extruder. 

Next, the drug and excipients must be blended or mixed together. It is very important at this stage that the bulk properties of the materials be conducive to mixing. This means that the materials must have good flowability characteristics. Lubricants such as magnesium stearate may be added to improve the flowability of the formulation. 

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