Tablet formulations flowability

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. 

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 the manufacture of tablets it is important to define and appreciate the physical properties of the active substance, in particular particle size and flowability. The technology involved in direct compression assumes great importance in tablet formulations because it is often the least expensive, particularly in the production of generics that the active substance permits. The limiting factors are the physical properties of the active substance and its concentration in the tablets. Even substances such as ascorbic acid, which are not generally suitable for direct compression owing to the friability of the crystals, can normally be directly pressed into tablets at concentrations of 30-40%. Ffowever, this technique is not as suitable if the content of ascorbic acid is higher. This limit may be shifted upward by special direct-compression auxiliaries, for example, Ludipress (BASF). 

The section on flowability discussed the role of glidants in tablet formulation. Glidants are one of three interrelated types of lubricant employed in solid dosage form manufacture. The two other classes of lubricant are antiadherent excipients, which reduce the friction between the tablet punch faces and tablet punches, and die-wall lubricant excipients, which reduce the friction between the tablet surface and the die wall during and after compaction to enable easy ejection of the tablet. 

It is generally agreed that one of the more important parameters of interest to formulators is the flowability of their powdered solids [57,58], The process-ability of these materials is greatly affected by flowability concerns, since the materials invariably need to be moved from place to place. For example when tablets are to be compressed at high speeds, the efficiency of the machine will only be suitable if the powder feed can be delivered at a sufficiently high rate. 

Microcrystalline Cellulose. Microcrystalline cellulose is a purified, partially depolymerized cellulose that occurs as a white, odorless, tasteless, crystalline powder composed of porous particles. It is widely used in pharmaceutical dosage forms, primarily as a filler-binder in oral tablets and capsules with both wet granulation and direct compression processes. Microcrystalline cellulose was marketed first in 1964 by the FMC Corporation under name Avicel PH in four different particle size grades, each with different properties.37 Addition of Avicel into a spray-dried lactose-based formulation overcame compressibility problems. At the same time, the lactose enhanced the flowability of the Avicel products available at that time. The direct compression tableting process became a reality, rather than a concept, partially because of the availability of Avicel. As of 2007, Avicel PH is commercially available in 10 types with different particle size, density, and moisture grades that have different properties and applications (Table 7.6).38 Other brands of microcrystalline cellulose are also available on the pharmaceutical market, including Pharmacel 101 and 102 from DMV International and Emcocel 50 M and 90 M from JRS Pharma. 

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... 

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... 

The importance of powder flow was emphasised in the section on Powder Flow. The formulation should have sufficient flowability to ensure that the appropriate quantity of powder flows into the dies of the tablet machine on a consistent basis. While the tests described for powder flow are useful development tools, the ultimate test of a formulation is the uniformity of weight of tablets manufactured on a production tablet machine. 

Spray-dried powders often exhibit relatively small particles representing a large surface area, low bulk density, and often show poor flowability. Therefore, often a pre-compaction step is needed during downstream processing in order to increase the bulk density to a level which later allows tablet compression or capsule filling. At the same time, this reduces the surface area of the material which could have an impact on the drug release rate, especially when appropriate attention is not given to the formulation composition. 

---