Tablet formulations compactibility

In order to produce an adequate tablet formulation, certain requirements, such as sufficient mechanical strength and desired drug release profile, must be met. At times this may be a difficult task for the formulator to achieve, due to poor flow and compactibility characteristics of the powdered drug. This is of particular importance when one only has a small amount of active material to work with and cannot afford to make use of trial-and-error methods. The study of the physics of tablet compaction through the use of instrumented tableting machines (ITMs) enables the formulator to systematically evaluate his formula and make any necessary changes. 

Khan, K.A., and Rhodes, C.T., Effect of variation in compaction force on properties of six direct compression tablet formulations, J. Pharm. Sci., 65 1835-1837 (1976). 

Sheskey P, Sackett G, Maher L, Lentz K, Tolle S, Polli J. Roll Compaction Granulation of a Controlled-Release Matrix Tablet Formulation Containing HPMC, Pharmaceutical Technology Tableting and Granulation Year book. Advanstar Communications, Pittsfield Mass. 1999 6-21. 

Sheskey P, Pacholke K, Sackett G, Maher L, Polli J. Roll compaction granulation of a controlled-release matrix tablet formulation containing HPMC. Pharm Technol 2000 24(ll) 30-52. 

The testing procedures used in this work have all been well described in the literature (4) and are focused on understanding the compression behavior of the powder samples and the mechanical properties of the resulting compacts. These methods are summarized in Table 1. For brevity, we have limited our initial studies to single component systems, but recognize that more work is needed in the future to understand the complex behavior of multicomponent mixtures. The current work should provide a sound basis for further work on such systems. It is intended that this treatise will enable pharmaceutical formulation scientists to better understand the similarities and differences between the most common grades and types of excipients, and will facilitate the rational selection of excipients for use in the development of immediate release tablet formulations. 

In summary, when tested, the grades of calcium phosphate dibasic discussed above exhibited mechanical properties that were very appropriate for tablet compaction and thus for formulation processing by direct compression, dry granulation, or wet granulation. With this in mind, it is easy to understand the popularity of DCP in pharmaceutical tablet formulations. 

The rate of tlie compaction process is another variable that should be considered throughout development, including scale-up. Typically, the development of a tablet formulation takes place on tablet presses that are relatively slow. The tableting rate is important to consider for several reasons. Blend flow is important to ensure bulk blend transfer into the tablet press (hopper) and consistent die fiU. Variation or difficulty in the bulk flow and die fill can contribute to tablet weight variation. As the compaction rate increases, the blended material must be able to... 

Lubrication is an important unit operation in manufacturing solid oral dosage forms, particularly when using a direct compression platform. Pharmaceutical lubricants can have a significant impact on product performance (e.g., disintegration and dissolution) as well as manufacturability. Lubrication is one of the most critical aspects of a tablet formulation. A lubricant is intended to reduce the friction between the tablet surface and die wall during and after compaction to enable easy ejection of the tablet. In low-dose dmg product development, three issues are associated with lubricating a direct compression formulation ... 

DuraSolv is Cima s second-generation fast-dissolving/disintegrating tablet formulation and is also produced using direct compression but using higher compaction... 

Basically, the process of tablet compression starts with the rearrangement of particles within the die cavity and initial elimination of voids. As tablet formulation is a multicomponent system, its ability to form a good compact is dictated by the compressibility and compactibility characteristics of each component. Compressibility of a powder is defined as its ability to decrease in volume under pressure, and compactibility is the ability of the powdered material to be compressed into a tablet of specific tensile strength [1,2], One emerging approach to understand the mechanism of powder consolidation and compression is known as percolation theory. In a simple way, the process of compaction can be considered a combination of site and bond percolation phenomena [5]. Percolation theory is based on the formation of clusters and the existence of a site or bond percolation phenomenon. It is possible to apply percolation theory if a system can be sufficiently well described by a lattice in which the spaces are occupied at random or all sites are already occupied and bonds between neighboring sites are formed at random. 

Force measurements made without displacement values are still useful in identifying the dependency of tablet hardness (and other associated characteristics) on compaction force, and also the effect of the tablet press compaction speed on tablet strength (influence of dwell time/effective contact time). Dwell time dependency is an important scale-up factor for the tableting process, and evaluation of the sensitivity of a formulation to dwell time at small scale is useful, although the actual commercial dwell time is not always achievable on instrumented, small-scale tablet presses. 

Traditionally, tablets have been made by granulation, a process that imparts two primary requisites to formulations compactibility and fluidity. Both wet granulation and dry granulation (slugging or roll compaction) are used (Table 1). Regardless of whether tablets are made by direct compression or granulation. 

Asgharnejad, M. Storey, D. Application of a compaction simulator to the design of a high-dose tablet formulation. Part I. Drug Dev. Ind. Pharm. 1996, 22 (9 10), 967-975. 

Dibasic calcium phosphate dihydrate is widely used in tablet formulations both as an excipient and as a source of calcium and phosphorus in nutritional supplements. It is one of the more widely used materials, 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 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, dibasic calcium phosphate dihydrate is abrasive and a lubricant is required for tableting, for example about 1% w/w of... 

Tribasic calcium phosphate is widely used as a capsule diluent and tablet filler/binder in either direct-compression or wet-granulation processes. The primary bonding mechanism in compaction is plastic deformation. As with dibasic calcium phosphate, a lubricant and a disintegrant should usually be incorporated in capsule or tablet formulations that include tribasic calcium phosphate. In some cases tribasic calcium phosphate has been used as a disintegrant. It is most widely used in vitamin and mineral preparations as a filler and as a binder. It is a source of both calcium and phosphorus, the two main osteogenic minerals for bone health. The bioavailability of the calcium is well known to be improved by the presence of cholecalciferol. Recent research reports that combinations of tribasic calcium phosphate and vitamin D3 are a cost-effective advance in bone fracture prevention. ... 

Lactose anhydrous has been used experimentally in hydrophilic matrix tablet formulations and evaluated for dry powder inhalation applications. Partial hydration of anhydrous lactose increases the specific surface area and reduces the flow properties of powders but has no effect on compactibility. A specification for lactose is included in the Food Chemicals Codex (FCC) see Factose, Monohydrate. The EINECS number for lactose anhydrous is 200-559-2. 

Sheskey PJ, Dasbach TP. Evaluation of various polymers as dry binders in the preparation of an immediate-release tablet formulation by roller compaction. Pharm Tcchnol 1995 19 98-112. 

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