Tablet manufacture direct compression

Strydom et al. [66] developed nanocoated cellulose used in the manufacture of tablets via direct compression. The research demonstrated that by coating cellulose microfibers with nanolayers of polyvinylpyrrolidone and poly(styrenesulfonate), the compaction properties of cellulose were dramatically improved without retarding the drug dissolution. Additional clear advantages were demonstrated, such as minimal weight gain of less than 1% as well as greater control over the surface properties of the fibers. 

Process ability Surface area, surface free energy, crystal defects, and deformation potential affect compressibility and machineability on high-speed tableting machines with reduced compression dwell times Particle size distribution and shape affect flow properties, efficiency of dry mixing process, and segregation potential Compressibility, flow ability, and dilution potential affect the choice of direct compression as a manufacturing process... 

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. 

Direct compression is a simpler alternative tablet manufacturing method. With direct compression, tablets are compressed directly from a powder mixture of an API and appropriate excipients. Like granulation methods, this approach is also based on the required flow, compressibility, and compactibility of a formulation. Direct compression offers both time and economic advantages by eliminating intermediate granulating and drying steps. 

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. 

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

If a low-dose dmg (< 1 mg per dose unit) is formulated as tablets or capsules, it can be very difficult to uniformly distribute a trace amount of dmg substance into a single unit dose, especially when direct compression is selected as the manufacturing platform. Major factors controlling the degree of homogeneity of the final blend are the mean particle size and the size distribution of dmg substance. It is often difficult to determine whether these factors are suitable for preparation of a low-dose dmg product.2 Generally, reduction of dmg substance particle size by milling or microni-zation is essential for a low-dose dmg product to meet the USP content uniformity criteria for tablets and capsules.3... 

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 ... 

Formulation design is based on the physical, chemical, and biopharmaceutical properties of a drug substance. A formulation for direct compression is composed of active pharmaceutical ingredients and other inactive ingredients such as fillers, binders, dis-integrants, flow aids, and lubricants. Simplicity is the basis of good formulation design. Minimally, a direct compression tablet formulation must meet requirements for manufacturability, uniformity of dose, physical and chemical stability, appropriate dmg release profiles, and bioavailability. In addition, the formulation must meet many quality standards and special requirements to ensure the efficacy and safety of the product. 

TABLE 7.11 Process Variables and Quality Attributes Using Direct Compression for Tablet Manufacture... 

Tablets are still considered as the dosage forms of choice for reasons such as low manufacturing cost and good stability. Many direct compression dilutents have been reported,but every dilutent has some disadvantages [295]. Crystalline cellulose (MCC) has been widely used as a tablet dilutent in Japan. Chitin and chitosan, on account of their versatility, were reported to be useful dilutents for pharmaceutical preparations [296-298].

EC is an inert, hydrophobic polymer that has been studied substantially for its application as a matrix-forming material in direct compression tablets. Direct compression is the preferred method of manufacture for producing tablets intended for immediate or sustained release. There have been reports on the compressibility and compatibility of EC [307-310] and on its use as a matrix-forming material in direct compression tablets for the delivery of soluble and poorly soluble drugs [311-316]. Tablet hardness [310,314,315], the particle size of the polymer [314,315,317], and the viscosity grade [313,314] were observed to directly affect the drug release rate. It was noted that tablet hardness affected the... 

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). 

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