Pharmaceutical applications excipients

The comprehensive profiling of drug substances and pharmaceutical excipients as to their physical and analytical characteristics remains at the core of pharmaceutical development. As a result, the compilation and publication of comprehensive summaries of physical and chemical data, analytical methods, routes of compound preparation, degradation pathways, uses and applications, etc., has always been a vital function to both academia and industry. 

A.J. O Neil, R.D. lee and A.C. Moffat, The application of multiple linear regression to the measurement of the median particle size of drugs and pharmaceutical excipients by near-infrared spectroscopy. Analyst, 123, 2297-2302 (1998). 

Since surface active betaine esters can be degraded under mild conditions and the hydrolysis products, i.e., the amino acid betaine and a long-chain alcohol can be expected to be less toxic than the intact surfactant, these am-phiphiles are interesting candidates for use in applications where surfactant toxicity is an issue. Surface active betaine esters have been evaluated as temporary bactericides [34] and have been studied as potential candidates for use as pharmaceutical excipients (pharmaceutical helper molecules) [30]. 

The conventional wisdom assumes that a pharmaceutical needs to be stable to be commercially successful. A more general look shows that the paradigm of the stability of APIs and pharmaceutical excipients as an indispensable property for their application is questionable. There are many examples (see Table 9.2 [46] and examples given above) demonstrating that good performance of a pharmaceutical within its field of application is not necessarily a contradiction to good degradability in the environment. 

Companies that manufacture food additives will often also produce an excipient grade. Many excipients first found application in processed foods where their demonstrated safety has made them attractive for use as pharmaceutical excipients. Examples of food additives also used in drug products include artificial sweeteners, antioxidants, and inorganic salts. 

In summary, the drug substance acceptance criteria should include information with respect to organic impurities, residual solvents, and inorganic impurities. Similar standards should also be applicable to pharmaceutical excipients. 

The mechanical strength of single microparticles relevant to pharmaceutical applications has been measured using compression testing by micromanipulation (Yap et al., 2006). Pharmaceutical excipients, comprising three enteric polymer particles Eudragit LI 00-55, Eudragit LI 00... 

Unacceptable starting materials used in research must be replaced by those which meet the regulatory quality and safety criteria. Reference to standard volumes of pharmaceutical ingredients and excipients should be made to decide whether a certain ingredient can be used. Standards are described in the pharmacopoeias of relevant countries, the "Handbook of Pharmaceutical Excipients" or its Swiss anchestor the "Katalog pharmazeutischer Hilfsstoffe". Fiedler s "Lexikon der Hilfsstoffe" (Lexicon of Excipients) provides many useful informations about the safety and about applications for excipients. (For references see Annex B to the registration requirements chapter.)... 

Additional non-synthetic colors may be acceptable for pharmaceutical applications based on previous precedence of use. These colors are typically listed in the Japanese Pharmaceutical Excipients (JPE) Directory along with their Japanese Pharmacopoeia (JP) or JPE specification. ... 

The parent CDs in Japan are classified as natural starches that have received approval by the Ministries of Health for use in foods. Relative to pharmaceutical applications, monographs for a- and p-CD have been included in the Japanese Pharmaceutical Excipients compendium (JPE). Even though nine pharmaceutical products with CD formulations have been marketed in Japan, the use of CDs has not been extensive enough in approved formulations to receive precedent status. ... 

In Japan, if the drug product contains an excipient with no precedence of use in that country, then the quality and safety attributes of the excipient must be evaluated by the Subcommittee on Pharmaceutical Excipients of the Central Pharmaceutical Affairs Council concurrently with the evaluation of the drug product application. Precedence of use means that the excipient has been used in a drug product in Japan, and will be administered via the same route and in a dose level equal to or greater than the excipient in question in the new application. 

In Japan, all these pathways to reduce ease the burden of introducing new excipients are more complex. If not already approved as a pharmaceutical excipient in Japan, food additives for oral administration or cosmetic substances for external application in drug formulations requires that they be treated as new excipients. For excipients already used in orally or intravenously administered products, a change to an externally applied product necessitates additional safety testing. Studies include acute and subacute toxicity (including adsorption through the skin) and local irritation investigations. ... 

Tbe Handbook of Pharmaceutical Excipients is a comprehensive, uniform guide to the uses, properties, and safety of pharmaceutical excipients, and is an essential reference source for those involved in the development, production, control, or regulation of pharmaceutical preparations. Since many pharmaceutical excipients are also used in other applications, the Handbook of Pharmaceutical Excipients will also be of value to persons with an interest in the formulation or production of confectionery, cosmetics, and food products. 

The Handbook of Pharmaceutical Excipients is a reference work containing a compilation of information on the uses and properties of pharmaceutical excipients, and the reader is assumed to possess the necessary knowledge to interpret the information that the Handbook contains. The Handbook of Pharmaceutical Excipients has no official status and there is no intent, implied or otherwise, that any of the information presented should constitute standards for the substances. The inclusion of an excipient, or a description of its use in a particular application, is not intended as an endorsement of that excipient or application. Similarly, reports of incompatibilities or adverse reactions to an excipient, in a particular application, may not necessarily prevent its use in other applications. Formulators should perform suitable experimental studies to satisfy themselves and regulatory bodies that a formulation is efficacious and safe to use. 

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