Tablet formulations manufacture

The influence of the actual manufacturing process can also affect the contribution of the diluent to the final characteristics of the product. For instance, Shah et al. [45] demonstrated that the release of drug from tablets formulated with soluble excipients may be more... 

The success in manufacturing the tablet formulation (with varying batch sizes of 250-900 kg) and achieving reproducible tablet physical results was due in part to the robustness of the formulation design and the active drug s compressibility characteristics. Illustration of the different particle size distributions observed and equipment parameters employed to achieve the desired results are noted in Tables 1 to 3 (1). 

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. 

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. 

The basic unit of any tablet press is tooling consisting of two punches and a die, called a station. The upper and lower punches come together in the die that contains the tablet formulation. Principally, two different types of machines are used, the eccentric and the rotary press. The eccentric press produces about 50-130 tablets per minute. The rotary press has a multiplicity of stations arranged on a rotating table with the dies. A few or many thousands of tablets can be produced per minute. There are numerous models of presses, manufactured by a number of companies, ranging in size, speed, and capacity. 

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 compression event is the central stage of tablet production. Compression not only depends on the machine but to a great deal on the material properties of a tablet formulation. The principal stages of compression have been described above. Principally, from the machine manufacturing side two different possibilities of compression exist. Either the lower punch is closing the die from the bottom side and the upper punch moves downward for compression or both upper and lower punches move simultaneously toward each other and the powder is compressed from both sides. In the first case the surface hardness of the tablet is not the same on the upper... 

In an attempt to overcome the previously noted problems with the sublingual tablet formulations, GTN is now widely available in metered-dose aerosol preparations. The sprays usually contain 0.4 mg GTN per unit dose. The manufacturers suggest that 1 or 2 metered doses be sprayed on the oral mucosa (preferably under the tongue) and then the mouth should be closed. 

There are three methods of tablet manufacture designed to confer these essential attributes to a tablet formulation. Wet granulation and direct compression are the most important, with dry granulation (also known as precompression or slugging) used in some circumstances. Fig. 1 shows the processes of wet granulation and direct compression broken down into their constituent stages. 

Tablet Evaluation Using Near-Infrared Spectroscopy / 3630 Tablet Formulation / 3641 Tablet Manufacture / 3653 Tablet Manufacture by Direct Compression / 3673 Tablet Press Instrumentation / 3684 Tablet Testing / 3707 Technology Transfer Considerations tor Pharmaceuticals / 3717...

Hlpasawa N, Ishise S, Miyata M, Danjo K. Application of nilvadipine solid dispersion to tablet formulation and manufacturing using crospovidone and methylcellulose on dispersion carriers. Chem Pharm Bull 2004 52(2) 244-247. 

In oral tablet formulations, P-cyclodextrin may be used in both wet-granulation and direct-compression processes. The physical properties of P-cyclodextrin vary depending on the manufacturer. However, P-cyclodextrin tends to possess poor... 

Huang Y, Khanvilkar KH, Moure AD, Hilliard-Lott M. Effects of manufacturing process variables on in vitro dissolution characteristics of extended-relca.se tablets formulated with hydroxypropyl methylcellulose. Drug Dev Ind Pharm 2003 29(l) 79-88. 

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