Excipients defined

For toxicological purposes, it may be inappropriate to define excipients as inert ingredients. It may be more appropriate to define an excipient as Any substance other than the active drug or pro-drug which has been appropriately evaluated for safety and is included in a drug delivery system to either ... 

The US. Pharmacopeia (USP XXII) or National Formula (NFXVII) (20) also provide a similar description however, the peroxide value is not defined (Table 9). These specifications are also given in the Handbook of Pharmaceutical Excipients (HPE), pubhshed jointiy by the American Pharmaceutical Association and The Pharmaceutical Society of Great Britain (21), which defines lecithins both from plants and eggs. The Merck Index (22) specifies a slightiy lower acid value. The Japanese Monograph (ISCI-II) (23) specifies a slightiy lower acetone-insoluble matter and a lower heavy-metal content. 

Bioavailability, Bioequivalence, and Pharmacokinetics. Bioavailabihty can be defined as the amount and rate of absorption of a dmg into the body from an adrninistered dmg product. It is affected by the excipient ingredients in the product, the manufacturing technologies employed, and physical and chemical properties of the dmg itself, eg, particle size and polymorphic form. Two dmg products of the same type, eg, compressed tablets, that contain the same amount of the same dmg are pharmaceutical equivalents, but may have different degrees of bioavailabihty. These are chemical equivalents but are not necessarily bioequivalents. For two pharmaceutically equivalent dmg products to be bioequivalent, they must achieve the same plasma concentration in the same amount of time, ie, have equivalent bioavadabihties. 

Analytical methods and specifications must be established and validated so as to define and control the quality and purity of the raw materials, intermediates and the finished product. For many standard chemical raw materials, the development of specifications will not be necessary as they are already published in US and European pharmacopoeia (for example, standards for water, organic solvents and various excipients). The ultimate objective of these activities is to be able to manufacture the drugs required for clinical trials in accordance with good manufacturing practice (GMP). 

As shown in the following table (from [3.6]) the selection of the excipient also defines Tg- and the amount of unfreezable water (UFW) in the glass phase. 

Table 13.8 lists the relevant sections of CFR 21 which govern excipients. Under Section 201(g)(1) of the Federal Food, Drug, and Cosmetic Act (FD C Act 1), the term drug is defined as ... 

The FDA guidance on IVIVC development and validation defines a number of circumstances where an IVIVC can be used to justify a biowaiver request in support of (1) level 3 process changes, (2) complete removal or replacement of non-release-controlling excipients, (3) level 3 changes in release-controlling excipients, (4) approval of lower strengths, and (5) approval of new strengths. Additionally, use of the IVIVC to justify biorelevant dissolution specifications is cited as the optimal approach. 

Thus, the impressive size of BASF s Fine Chemical Division is due to a BASF-specific definition of the term fine chemicals. In fact, the division, which is part of the business segment Agricultural Products Nutrition produces large volume aroma chemicals (a.o. 40,000 metric tons/year of citral) and vitamins (A, B2, C and E), as well as several lines of specialty chemicals (a.o. excipients and personal care products). Fine chemicals as defined in Section 1.1 account for about 150 million ( 190 million) in 2006, after full consolidation of the Swiss Fine Chemical company Orgamol, acquired in 2005. BASF holds a leading position in ibuprofen (made in USA), coffein and pseudoephedrin (made in Germany). BASF forecasts a further increase to 500 million ( 625 million) within 10 years which should make it the third largest fine-chemical company. 

The answer is not too difficult, as it is based on identified physical principles. A correct comparison between two formulations is often a prerequisite, as the dissolution process of the active substance in the final granulate or tablet can be affected both by the amount of granulating liquid and the qualitative change (excipients) in the formulation. In order to calculate corresponding, i.e., similar amoimts of granulating liquid in different compositions, it is necessary to introduce a dimensionless amount of granulating liquid n. This amount n can be defined as degree of saturation of the interparticulate void space between the solid material (Fig. 2). 

The discipline of analytical chemistry is wide and catholic. It is often difficult for a food chemist to understand the purist concerns of a process control chemist in a pharmaceutical company. The former deals with a complex and variable matrix with many standard analytical methods prescribed by Codex Alimentarius, for which comparability is achieved by strict adherence to the method, and the concept of a true result is of passing interest. Pharmaceuticals, in contrast, have a well-defined matrix, the excipients, and a well-defined analyte (the active) at a concentration that is, in theory, already known. A 100-mg tablet of aspirin, for example, is likely to contain close to 100 mg aspirin, and the analytical methods can be set up on that premise. Some analytical methods are more stable than others, and thus the need to check calibrations is less pressing. Recovery is an issue for many analyses of environmental samples, as is speciation. Any analysis that must... 

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