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.
Highlights
In order to harvest the maximum therapeutic activity of the drug molecules, appropriate dosage forms are designed using various additives called ‘Excipients’ (Rowe et al 2009)
Recommendations Though the above facts are well known, a system to classify excipients on the basis of their in vivo functionality and ability to significantly influence the therapeutic activity of co-formulated drugs or their use as atypical active pharmaceutical ingredients is still unavailable
It is recommended that a broad ‘Excipient Classification System’ (ECS) be considered and introduced to segregate the excipients used as formulation and manufacturing aids from those affecting the absorption, distribution, metabolism, and elimination (ADME) and PK/PD properties of the co-administered drugs
Summary
In order to harvest the maximum therapeutic activity of the drug molecules, appropriate dosage forms are designed using various additives called ‘Excipients’ (Rowe et al 2009). The appropriate selection and use of excipients to deliver drugs is dependent on the requirements during fabrication, desired dissolution and release profile, organoleptic characteristics of the formulation, drug stability and overall physiochemical characteristics. As indicated, certain excipients exhibit biological activity by inhibiting metabolic enzymes in the gut wall and intestinal efflux pumps (Constantinides et al 2007; Chen 2008). If used intentionally, such excipients by virtue of their ability to increase the drug’s solubilization capacity in the intestine, metabolic stability and membrane transport may prove to be extremely useful to improve bioavailability; otherwise it may result in severe
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