Excipients information

The USP/NF provides a listing of excipients by categories in a table according to the function of the excipient in a dosage form, such as tablet binder, disintegrant, and such. An excellent reference for excipient information is the APA s Handbook of Pharmaceutical Excipients (1994). 

The U.S. Food and Drug Administration (FDA) defines novel (new) pharmaceutical excipients as those substances used in the United States for the first time in a human drug product or by a new route of administration (1). The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) includes sections in its Common Technical Document (CTD) that details the information required for the approval of novel (new) excipients. Information on the control of excipients is included in Section P.4 of the CTD, and any additional information that may be required should be included in Appendix A.3 of the CTD. 

The tests suggested by IPEC-Americas are summarized in Table 1. The R represents required tests and the C represents tests that are conditional based on intended use and the results of previous tests. The tests suggested by IPEC-Europe are found in Table 2 and differ slightly from Table 1. The decision whether or not to perform C labeled tests requires the judgment of a trained professional. Both IPEC test models are also predicated on obtaining chemical, pharmacological, and physical data from other investigators involved in the development of candidate excipients. Information... 

Section 9, Pharmacopeial Specifications, briefly presents the compendial standards for the excipient. Information included is obtained from the British Pharmacopoeia (BP), European Pharmacopeia (PhEur), Japanese Pharmacopeia (JP), and the United States Pharmacopeia/National Formulary (USP/ USPNF). Information from the JP, USP and USPNF are included if the substance is in those compendia. Information from the PhEur is also included. If the excipient is not in the PhEur but is included in the BE, information is included from the BP. Pharmacopeias are continually updated with most now being produced as annual editions. However, although efforts were made to include up-to-date information at the time of publication of this edition, the reader is advised to consult the most current pharmacopeias or supplements. 

AugsburgerL, Hoag S (2008) Pharmaceutical dosage forms rational design and formulation with excipients. Inform Healthcare, New York... 

This book series comprises of 38 volumes. It crnitains information about 533 substances and excipients. The Profiles series include for instance the physical and analytical characterisation of substances and excipients, information of clinical uses, pharmacology, pharmacokinetics, safety or toxicity. The first 29 volumes were published by the name Analytical Profiles of Drag Substances. Since volume 30 the name was changed into Profiles of Drag Substances, Excipients and Related Methodology. It is recommended for its chemical, physico-chemical and stability information. Published by Academic Press... 

Eorensic science laboratories may have different missions and therefore conduct different types of testing on samples (21,22). Eor example, the United States Department of Justice, Dmg Enforcement Administration (DEA) forensic laboratories assist authorities ia criminal intelligence-gathering efforts. As such, DEA chemists routinely analyze both the iUicit dmg and excipient, the material used ia the cutting or diluting of the pure dmg, ia a given specimen. The excipient may provide information as to where the sample was produced. 

Appendices This section is most likely to contain additional data associated with biological-based products. It should contain information as regards the facilities and equipment used for the manufacture of biotech products. Assessment of the risk of contamination from adventitious agents such as transmissible spongiform encephalopathy agents (TSEs), bacteria, mycoplasma, fungi or viruses should also be provided. Additional information on novel excipients that have not been used before should also be included in this section. 

Development pharmaceutics information is intended to cover a number of aspects related to the active ingredient(s), excipients, container-closure system, and the finished (drug) product. These aspects will be considered individually below. 

The compatibility of the active ingredient with other active ingredients and excipients should be demonstrated. Preformulation study reports often provide useful relevant information. Preliminary stability study reports may be used as supporting data. 

In addition to the information relating to excipients in the development pharmaceutics guidelines there are two guidelines that specifically address excipients in pharmaceutical products—3AQ9a (adopted February 1994) and EMEA/CVMP/004/98 Final (adopted February 1999). These expand on the information in the development pharmaceutics guidelines. 

In the case of an excipient that contains a mixture of constituents, qualitative and quantitative details of the composition should be provided (other than for flavoring or aromatic products, which must state the information only qualitatively provided there is a suitable method for ensuring consistency of composition and of the presence of the main ingredients and any carriers, with relevant references to purity criteria such as those established by the World Health Organization Food and Agriculture Organization). 

Upper and lower acceptance limits are expected for all ingredients—these would normally be nominal 5% for active ingredients and nominal 10% for excipients, with wider ranges being individually justified. Where factorization is used, the details should be included, together with information on total mass adjustment if necessary. Overages need to be stated and justified in the development pharmaceutics section. 

In the present work, such a systematic approach to the physical characterization of pharmaceutical solids is outlined. Techniques available for the study of physical properties are classified as being associated with the molecular level (properties associated with individual molecules), the particulate level (properties pertaining to individual solid particles), and the bulk level (properties associated with an ensemble of particulates). Acquisition of this range of physical information yields a total profile of the pharmaceutical solid in question, whether it is an active drug, an excipient, or a blend of these. The development of a total profile is a requirement for successful manufacture of any solid dosage form. 

In addition to the studies listed in Figure 4.5, stability characteristics of the protein with regard to e.g. temperature, pH and incubation with various potential excipients are studied. Such information is required in order to identify a suitable final product formulation, and to give an early indication of the likely useful shelf-life of the product (Chapter 6). 

Additional information often presented includes the name of the manufacturer, a list of excipients included and a brief summary of the correct mode of product usage. 

Our laboratory data processing system is known as STRIDE (System to Retrieve Information from Drug Evidence). It is now in its third year of operation. In 1974, we will be installing in each laboratory computer terminals connected to the main computer in Washington. Every piece of evidence analyzed is entered into the system. The type of information includes the subject s name where the purchase or seizure was made the amount of money expended the suspected drug what the drug was found to bfe the purity of the drug and what excipients and adulterants were present. 

Available and commonly used vehicles and formulating agents are reviewed along with basic information on their characteristics and usages, in Section 13.8 at the end of this chapter. There is a general presumption that those excipients and... 

Information on existing or new excipients can be described and provided to the FDA in an NDA directly. Alternatively, the manufacturers of excipients may prepare and submit type IV Drug Master Files (DMF) to support the use of an excipient in one or more NDAs. The DMFs are discussed in FDA s regulations under 21 CFR Section 314.420 and the FDA-issued Guidance for Drug Master Files (8). When authorized by the DMF submitter (i.e., the excipient manufacturer) and cross-referenced by an NDA submitter, the FDA reviews the DMF to make determinations on the safety, manufacture, and quality of the excipient use in the new drug that is the subject of the then pending NDA. The DMF becomes active when reviewed in conjunction with the review and approval of an NDA. 

A pharmacopeia is a collection of recommended specifications and other information for therapeutic products, including drug substances (active ingredients), excipients, dosage forms (also called preparations), and other articles. One function of a pharmacopeia is to provide a uniform and public basis on... 

While there are limitations associated with the use of an in vitro permeability model for assessing the transport of compounds across the buccal mucosa, it can still be useful in assessing and comparing the permeability of compounds under different conditions, such as pH, temperature, and osmolarity, which provide valuable information on the mechanisms involved in drug transport. Additionally, the preliminary effects of potential chemical penetration enhancers or formulation excipients may be assessed, and these may provide a substantial rationale for subsequently assessing the effect of these agents in man. 

The study of reaction rates or kinetics of a particular denaturation process of a protein therapeutic can provide valuable information about the mechanism, i.e., the sequence of steps that occur in the transformation of the protein to chemically or conformationally denatured products. The kinetics tell something about the manner in which the rate is influenced by such factors as concentration, temperature, excipients, and the nature of the solvent as it pertains to properties of protein stability. The principal application of this information in the biopharmaceutical setting is to predict how long a given biologic will remain adequately stable. 

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