Additives in Excipients

A number of excipients contain additives that serve as stabilizers or to improve material properties. Stabilizers can themselves affect drug stability, 

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Perhaps a more specialized case of using plasticizers in acrylic formulations can be found in drug delivery patches. Here, plasticizing additives called excipients... 

The different salts, esters, ethers, isomers, mixtures of isomers, complexes or derivatives of an active substance shall be considered to be the same active substance, unless they differ significantly in properties with regard to safety and/or efficacy, in which case additional safety and efficacy data are required. The same qualitative and quantitative composition only applies to the active ingredients. Differences in excipients will be accepted unless there is concern that they may substantially alter the safety or efficacy. The same pharmaceutical form must take into account both the form in which it is presented and the form in which it is administered. Various immediate-release oral forms, which would include tablets, capsules, oral solutions and suspensions, shall be considered the same pharmaceutical form for this purpose. 

The process of formulation for any of the above is generically the same, beginning with some form of product specification and ending with one or more formulations that meet the requirements. Correct choice of additives or excipients is paramount in the provision of efficacy, stability, and safety. For instance, the excipients may be chemically or physically incompatible with the drug or they may exhibit batchwise variability to such an extent that at the extremes of their specification they may cause failure in achieving the desired drug release profile. In addition, some excipients, especially those that are hydroscopic, may be contraindicated if the formulation is to be manufactured in tropical countries. Flence formulators must work in a design space that is multidimensional in nature and virtually impossible to conceptualize. 

In 21 CFR Section 210.3(b)(8)(2), an inactive ingredient means any component other than an active ingredient. According to the CFR, the term inactive ingredient includes materials in addition to excipients. 21 CFR Section 201.117 states... 

For any new excipients, APIs or drug products (where new does not necessarily mean novel, but new to the receiving site) there are additional testing criteria, e.g. supplier audits, third-party contract laboratory audits, analytical method transfers, sample management/tracking, etc. For those key excipients, where there is on-site historical experience, it still behoves both parties to check whether the local grade/supplier used by the CMO is equivalent to that used by the supplier (Worsham, 2010). There are many examples of differences in excipient physical properties, e.g. particle size, which have been attributed to different excipient sources that could ultimately impact on the performance of those excipients in formulated products (Frattini and Simioni, 1984 Dansereau and Peck, 1987 Phadke et al., 1994 Lin and Peck, 1994). 

Once the protein is purified, it will be formulated to produce the drug product. This could be as simple as diluting the protein in phosphate-buffered saline, or as complex as addition of excipients and lyophilization. The mark of... 

Most drugs that are prescribed to us are formulated with active pharmaceutical ingredients and excipients. The formulations of selected drugs are presented in Exhibit 5.11. According to the US Pharmacopoeia and National Formulary definition, excipients are any component, other than the active substance(s), intentionally added to the formulation of a dosage form. There are many reasons for the addition of excipients ... 

In API manufacture, whether via chemical synthesis, rDNA technology, or extraction from natural products, there are significant changes (physical and chemical) from the starting materials to the API. In the formulation process, however, the quality and specifications of the API are retained. The addition of excipients to produce the drug product in a finished dosage form does not present physical or chemical changes to the API. 

Many pharmaceutical excipients are food additives or GRAS substances that have been used in foods for many years. The Handbook of Excipients provides information in the regulatory status section for the accepted uses of excipients in foods (27). In addition, Appendix II of the Handbook lists the E number for excipients that are approved as food additives in the EU. 

The presence of additives in the excipient is another issue that can directly influence our understanding of how a particular excipient interacts. The inclusion... 

Specific formulation strategies need to be employed for macromolecule compounds. An excellent review of protein stability in aqueous solutions has been published by Chi et al. (92). In addition to solution stability of proteins and peptides, aerosolization may result in significant surface interfacial destabilization of these compounds if no additional stabilization excipients are added. This is due to the fact that protein molecules are also surface active and adsorb at interfaces. The surface tension forces at interfaces perturb protein structure and often result in aggregation (92). Surfactants inhibit interface-induced aggregation by limiting the extent of protein adsorption (92). 

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