Monographs for excipients

Progress on the comparison of monographs for excipients published in The International Pharmacopoeia and those adopted in the Pharmacopoeial Discussion Group (PDG) process was noted. The Committee was pleased to note the offer of technical assistance by the International Pharmaceutical Excipients Council (IPEC). 

---

Unfortunately, the standards for the same raw material can vary in different pharmacopoeias, and so the choice of pharmacopoeia will depend on the intended market for the product (see later comments about harmonisation of standards). Suppliers should provide materials that comply with the specified pharmacopoeial standards. Monographs for excipients provide minimum tests and specifications, which can save time and resource negotiating new specifications with the regulatory authorities. Even so, the user may have to do additional tests to show that the excipient is suitable for use in a particular product or drug delivery system. 

United States Pharmacopeia and The Natiraial Formulaiy (USP-NF) is a combination of two compendia USP and the NF. USP contains monographs for substances, dosage forms and medicines. Dietary supplements monographs are in a separate section of the USP. NF discusses monographs for excipients. 

In contrast to aspirin itself, the U.S.P. monograph for aspirin tablets has undergone considerable changes. For some reason, U.S.P. does not use the ferric salt test for free salicylic acid, as does the British Pharmacopeia of 1973. Apparently, certain excipients such as citric and tartaric acid interfere with this reaction.77 Already in 1913, a double titration method was developed78 which was made an official method in 1926.79 This method was used as the assay method when the aspirin tablets monograph was introduced into U.S.P. XII in 1942. 

It also asked respondents to identify the specifications, tests, and assays in the monographs for these excipients that are most important to be harmonized. 

The existing structure for review of excipient ingredients has several structural defects that result in significant disincentives in the development of novel excipients. Currently, only excipients that have been approved in an NDA are subject to a USP/NF monograph, or excipients that have an FDA- or a JECFA-sanctioned food... 

Monograph for Calcium Phosphate, Dibasic Dihydrate from Handbook of pharmaceutical excipients. London Pharmaceutical Press, 2004. 

The International Pharmaceutical Excipient Council in the United States (Arlington, Virginia 703-521-3338) has issued a GMP guideline for excipient bulk pharmaceutical chemicals. In conjunction with both the European and Japanese Pharmaceutical Excipient Councils, the council is currently engaged in establishing international harmonization excipient monographs for the more popular pharmaceutical excipients. A list of important and popular pharmaceutical excipients is given in Table 1. 

The harmonization effort encompasses not only monographs for individual excipients but also general tests. An overlap with notorious GMP and validation... 

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. ... 

Japanese Pharmaceutical Excipients, which has 206 monographs for pharmaceutical excipient. 

Specifications for excipients Pharmacopoeia copy of the monograph, test methods referenced Additional specifications Non-pharmacopoeia list of tests and for each excipient, including solvents, liquids to adjust pH, coatings, capsule shell, and inked imprint (on the dosage form), description of test methods, microbiological limits, colours EU/FDA/Japan ... 

All excipient tables (3, 4,5) were produced using US FDA Center for Drug Evaluation and Research Inactive Ingredient List for Approved Drug Products, updated 10/31/2005, along with product monographs for respective listed products. 

This guideline mainly addresses the harmonization of monographs for commonly used excipients, across the United States, European, and Japanese pharmacopeias. Prior to harmonization, manufacturers were required to perform different or replicate tests with different acceptance criteria on many... 

Long-chain unsaturated oils such as fatty acid esters are used in a number of semisolid and liquid products. It is known from the use of these oils that the double bonds in their chemical structure can react with oxygen to form peroxides and/or hydroperoxides. Some compendial monographs for these materials will have specifications to limit the level of peroxide for this reason. For active ingredients that are easily oxidized, these excipients may need to be avoided to minimize the catalytic oxidation of the active ingredient and to maximize the stability of the drug product. 

Excipients are normally considered to be acceptable if they are listed in the major pharmacopoeias from the United States, Europe and Japan. There has been much progress in harmonising the monographs for key excipients in these pharmacopoeias. For products being... 

Various pharmacopoeias, e.g., United States/National Formulary British, European, Japanese, Pharmacopoeias Martindale, The Extra Pharmacopoeia The Merck Index The British Pharmaceutical Codex Include standards and monographs for drugs, excipients, containers/closures and medical devices Updated regularly many available in book format or CD-ROM can be obtained through various publishers including Interpharm... 

---