Considerations and recommendations on traditional and non-traditional uses of excipients in oral drug products

Abstract

Excipients represent diverse classes of molecules, small molecules or macromolecules, with versatile structures within a given class and are from natural, semi-synthetic and synthetic sources. They are essential ingredients in drug products independently of the route of administration where both traditional and non-traditional uses are present. Beyond their traditional use as formulation and manufacturing aids, certain excipients exhibit biological effects and thus can be used either as atypical active pharmaceutical ingredients alone or synergistically with conventional active pharmaceutical ingredients to affect the overall pharmacokinetics/ pharmacodynamics and therapeutic effect(s) of the co-administered drug(s). In reference to oral drugs, biological effects of the excipients that contribute to improved drug absorption and pharmacokinetics include their ability to modulate drug dissolution, intestinal membrane permeability, gut wall metabolism and efflux pumps. These non-traditional uses of excipients are illustrated in representative case studies from published literature. From a drug development and regulatory perspective, it is apparent that an appropriate excipient classification system is considered which is applied to new uses of existing excipients as well as to the development of novel excipients and segregates biologically active excipients from the larger pool of excipients. This classification system should be a useful tool to pharmaceutical scientists and its successful implementation and broader acceptance requires input and ownership from all major stakeholders, that is, the excipient manufacturers, the end users, excipient forums and discussion groups such as the International Pharmaceutical Excipients Council (IPEC) and regulatory agencies.

Biopharmaceutical aspects and implications of excipient variability in drug product performance

“…Excipients constitute a major component of final products and it is recognized that variability in their material properties can impact product processing, manufacturing and performance [2,3]. The exact mechanisms by which excipients exert their action are still to be discovered, especially when drug product performance is concerned [4,5]. The gastrointestinal heterogeneity and its effect on excipient functionality is an additional challenge in understanding and controlling the role of excipients in drug release.…”

Drug Transporters

“…In tablets, for example, the addition of disintegrating agents may improve the dissolution rate of a drug. Surfactants, such as Tween-80, can increase the solubility of poorly soluble drugs while improving drug permeability (Constantinides et al 2016). Another example is enteric coatings, which resist the action of gastric fluids and disintegrate when the pH is increased at the intestinal level, thus preventing the acid degradation of certain drugs.…”