Compression and roller compaction

A. Gupta, G.E. Peck, R.W. Miller and K.R. Morris, Influence of ambient moisture on the compaction behavior of microcrystalline cellulose powder undergoing uni-axial compression and roller compaction a comparative study using near-infrared spectroscopy, J. Pharm. Sci., 94(10), 2301-2313 (2005). 

Within the pharmaceutical industry, granulation is a widely used process to prepare drug substance and excipient particles for compression. " There are wet and dry granulation procedures herein high shear wet grannlation, fluid bed granulation and roller compaction will be discussed. 

Compared to wet granulation and roller compaction, the direct compression platform allows tablet manufacture with fewer unit operations, as listed in Table 7.1. The sections that follow discuss several advantages and disadvantages of using direct compression for tablet manufacture. 

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. 

Dry compaction technique like roller compaction is experiencing renewed interest in the industry. There are a number of drug substances which are moisture sensitive and cannot be directly compressed. The roller compaction provides suitable alternative technology for processing these products. 

Pellet Mills. Pellet mills differ from roU briquetting and compacting machines in that the particulates are compressed and formed into agglomerates by extmsion through a die rather than by squeezing as they are carried into the nip between two roUs. Several types of equipment that use the extmsion principle are available. The die may be a horizontal perforated plate with rollers acting on its upper surface to press material through the plate. 

An advantage of roller compaction is the increase in bulk density resulting in a reduced tablet size. It can also be used to improve the content uniformity of low-dosage compounds. Characteristics which afifect the tabletability of roller compacted formulas include over-lubrication and precompression of the compact. Typically, the powder is roller compacted between 15 and 40 kN of force prior to tablet compression. 

Ejection forces are relatively higher for roller compaction tablets, although similar to direct compression. Ejection forces are usually 100-400 N, depending on the tablet weight and shape, as shown in Figure 26. 

Therefore, for a given formulation (brittle vs ductile), a balance in the level of applied compaction force and roller gap width must be identified to control factors that influence tablet content uniformity (variability in sieve cut potency, sifting, and fluidization segregation) without sacrificing factors that influence manufacturability (compression force required to achieve target tablet hardness). 

TABLE 7.1 Comparative Unit Operations in Tablet Manufacture Using Wet Granulation, Roller Compaction, and Direct Compression... 

Diluents, although commonly presumed inert, do have the ability to influence the stability or bioavailability of the dosage form. For example, dibasic calcium phosphate (both anhydrous and dihydrate forms) is the most common inorganic salt used as a filler-binder for direct compression. It is particularly useful in vitamin products as a source of both calcium and phosphorous. Milled material is typically used in wet-granulated or roller-compacted formulations. The coarse-grade material is typically used in direct compression formulations. It is insoluble in water, but its surface is alkaline and it is therefore incompatible with drugs sensitive to alkaline pFI. Additionally, it may interfere with the absorption of tetracyclines [7]. 

After the compression and consolidation of the powder in the die, the formed compact must be capable of withstanding the stresses encountered during decompression and tablet ejection. The rate at which the force is removed (dependent on the compression roller diameter and the machine speed) can have a significant effect on tablet quality. The same deformation characteristics that come into play during compression play a role during decompression. 

The surface of milled anhydrous dibasic calcium phosphate is alkaline and consequently it should not be used with drugs that are sensitive to alkaline pH. However, reports suggest there are differences in the surface alkalinity/acidity between the milled and unmilled grades of anhydrous dibasic calcium phosphate the unmilled form has an acidic surface environment. This difference has important implications for drug stability, particularly when reformulating from, e.g. roller compaction to direct compression, when the particle size of the anhydrous dibasic calcium phosphate might be expected to change. 

Tribasic calcium phosphate occurs naturally as the minerals hydroxylapatite, voelicherite, and whitlockite. Commercially, it is prepared by treating phosphate-containing rock with sulfuric acid. Tribasic calcium phosphate powder is then precipitated by the addition of calcium hydroxide. Tribasic calcium phosphate is alternatively prepared by treating calcium hydroxide from limestone with purified phosphoric acid. It may also be obtained from calcined animal bones.Some tribasic calcium phosphate products may be prepared in coarser, directly compressible forms by granulating the powder using roller compaction or spray drying. 

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