Brittle excipient

Brittle fracture indices were obtained for a series of compacted direct compression excipients that had been exposed to various degrees of ambient relative humidity [67], As illustrated in Fig. 9, compacts of the essentially... 

Lot to lot variations of several drugs and excipients are shown in Table 9. Specially crystallized lots of ibuprofen, for example, show substantial changes in Brittle Fracture and Bonding Indices. Phenacetin shows a significant increase in brittleness at higher relative humidity. It was observed by Hiestand and Smith [31] that compacts of dried phenacetin did not fracture, while the lot equilibrated at 40% relative humidity did, consistent with the Brittle Fracture Index change. 

All three grades of mannitol showed similar, relatively low BFI values. This low tendency for brittle fracture represents a very significant advantage of mannitol, particularly with direct compression formulations where material properties, and not powder processing, must be used alone to overcome deficiencies of the API and other ingredients. It should be remembered that low BFI is but one consideration of many when selecting excipients for direct compression formulations. 

As shown in Table 6.17, the hardness—compression force profile for Drug A tablets is linear across the range of compression forces studied. This linear profile is attributed to the properties inherent in the brittle and ductile excipients chosen for this formulation. In contrast, the hardness—compression force profile for Drug B shows a plateau in tablet hardness at higher compression forces (> 11 kN), as listed in Table 6.18. 

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. 

Available as anhydrous and monohydrate anhydrous material used for direct compression due to superior compressibility Originally direct-compression excipient, now often included in granulations due to its excellent compressibihty Direct-compression diluent, often used in chewable tablets Was widely used as sweetener/filler in effervescent tablets and chewable tablets less popular nowadays due to cariogenicity Versatile material that can be used as diluent binder, and disintegtant Brittle material... 

The deformation properties of the drug substance and excipients will have a direct influence on the strength of the tablets that are produced by direct compression. The type of deformation that occurs will depend upon the material s inherent properties and the amount of force being applied. Deformation can be described in three main ways elastic, plastic, and brittle fragmentation, but it is important to realize that these are idealized deformation mechanisms— most real materials are some combination of two or all three mechanisms. Processes such as wet granulation, melt extrusion, and roller compaction can be used to improve compaction properties and reduce formulation sensitivity to changes in raw material quality. 

Anhydrous dibasic calcium phosphate is used both as an excipient and as a source of calcium in nutritional supplements. It is used particularly in the nutritional/health food sectors. It is also used in pharmaceutical products because of its compaction properties, and the good flow properties of the coarse-grade material.The predominant deformation mechanism of anhydrous dibasic calcium phosphate coarse-grade is brittle fracture and this reduces the strain-rate sensitivity of the material, thus allowing easier transition from the laboratory to production scale. However, unlike the dihydrate, anhydrous dibasic calcium phosphate when compacted at higher pressures can exhibit lamination and capping. This phenomenon can be observed when the material represents a substantial proportion of the formulation and is exacerbated by the use of deep concave tooling. This phenomenon also appears to be independent of rate of compaction. 

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