Tablet manufacturing parameters

SS Kornblum, JO Hirschorn. Dissolution of poorly water-soluble drugs I. Some physical parameters related to method of micronization and tablet manufacture of a quinazolinone compound. J Pharm Sci 59 606-609, 1970. 

TABLE 2.6 Typical Unit Operations, Process Parameters, and Quality Attributes for Tablet Manufacture... 

TABLE 5.4 Process Parameters and Uniformity Data for Tablets Manufactured Using Different Granulation Methods... 

Various approaches can be used to solve picking and sticking problems during tablet manufacturing, namely optimization of press tooling, process parameters, and formulation. Generally, it is important to find the optimal combination of formulation and process parameters, particularly when market image tablets are to be produced. 

While blending times and tablet press parameters may not be fully established for early phase clinical supply manufacturing of solid oral dosages, those variables have a much lower potential to directly affect product safety than sterility, endotoxin contamination, or objectionable types and levels of particulates do for sterile, parenteral clinical supplies. Because clinical supplies can be incompletely characterized, and are usually given to patients already in weakened conditions, those processes and their related validation data necessary to guarantee patient and product safety (e.g., sterilization and aseptic fill) are expected to be in place as early as Phase I clinical supply manufacture. ... 

Compaction simulators are most commonly used to replicate the compaction process of a rotary tablet press. Manufacturing parameters, such as production speed, dwell lime, compression force, precompression force are often studied using a relatively small quantity of bulk powder. These parameters can significantly affect tablet crushing strength, friability, and disintegration time. The relationship among compaction pressure. 

Kornblum SS and Hirschorn JO. Dissolution of Poorly Water-Soluble Drugs. 1 Some Physical Parameters related to Method of Micronization and Tablet Manufacture of a Quinazoline Compound./PAarro Sci 1970 59 606-609. 

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). 

Subsequent to these successful pilot scale trials, the formulation was scaled-up to the production launch site. Once again, only those parameters recognized as critical were modified during manufacture. The compression parameters that were modified were speed and hardness. A total of four production-sized batches were manufactured, with the first batch being compressed on a 43 station Fette 2080 rotary tablet press, and three subsequent batches compressed on a 36 station Fette 2090 rotary tablet press. Three compression speeds and three compression forces were successfully evaluated... 

In drug preparations, sensitivity is not a particular problem as there is always sufficient of the active constituent present. Suitable extraction procedures should be carried out and each fraction should then be subjected to chromatographic analysis. The mass spectra, together with the appropriate retention parameters, may then be used for identification purposes. In many cases mass spectrometric analysis is undertaken as confirmation of an identification based on the physical characteristics such as size, colour, markings, etc., of the tablet or capsule. Mass spectrometry may be used not only to identify the major components but also the trace impurities. This information may be used for quality control purposes, and may enable the route of manufacture of certain drugs to be determined. 

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