Tableting process of pharmaceutical products

If you are in charge of quality control laboratories in manufacturing companies, it is important to distinguish between the variability of a product and the variability of the analysis. When analyzing tablets on a pharmaceutical production line, variability in the results of an analysis has two contributions from the product itself and from the analytical procedure. Your bosses are interested in the former, and you, the analyst, must understand and control the latter. It is usually desired to use methods of analysis for which the repeatability is much less than the variability of the product, in which case the measured standard deviation can be ascribed entirely to the product. Otherwise, analysis of variance can be used to split the total variance of duplicate results into its components (chapter 2). In the discussion that follows, the emphasis is on measurement variability, but the principle is the same, and the equations and methods can be used directly to obtain information about the product or manufacturing process. 

Common pharmaceutical products of olibanum and salai guggul are tablets prepared from dried extracts of boswellic adds, which are obtained by processes involving treatment of the resins with alkali and acid. The stress involved in this treatment is expected to lead to alteration of some triterpenes as, e.g., the conversion of the unstable 3-(9-acetyl-ll-hydroxy-[3-boswellic acid (compound 12) to the stable compound 3-(9-acetyl-9,ll-dehydro-[3-boswellic acid (compound 13). Two-dimensional TLC is an excellent means of observing this conversion [5]. For verification of this process, the substances have to be isolated by PLC and identified by GC-MS. 

Other applications of the previously described optimization techniques are beginning to appear regularly in the pharmaceutical literature. A literature search in Chemical Abstracts on process optimization in pharmaceuticals yielded 17 articles in the 1990-1993 time-frame. An additional 18 articles were found between 1985 and 1990 for the same narrow subject. This simple literature search indicates a resurgence in the use of optimization techniques in the pharmaceutical industry. In addition, these same techniques have been applied not only to the physical properties of a tablet formulation, but also to the biological properties and the in-vivo performance of the product [30,31]. In addition to the usual tablet properties the authors studied the following pharmacokinetic parameters (a) time of the peak plasma concentration, (b) lag time, (c) absorption rate constant, and (d) elimination rate constant. The graphs in Fig. 15 show that for the drug hydrochlorothiazide, the time of the plasma peak and the absorption rate constant could, indeed, be... 

Ensuring homogeneous mixing of the components (APIs and excipients) of a pharmaceutical preparation is a crucial prerequisite for obtaining proper solid dosages (tablets and capsules). Pharmaceutical manufacturers invest much time, labor and material resources in this process. Blending is intended to ensure uniform distribution of all components in the end products,so that each dose wiU contain the correct amount of the active ingredient. 

Tableting process, since being introduced in the early 1840s, has witnessed numerous changes in the form of stringent regulatory requirements for the excipients and product stability. Increasing regulatory pressure on purity, safety, and standardization of the excipients has catalyzed the formation of an international body, the International Pharmaceutical Excipients Council (IPEC) (13). IPEC is a tripartite council with representation from the United States, Europe, and Japan, and has made serious efforts to harmonize requirements for purity and functionality testing of excipients (14).

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