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By: Panayiotis P. Constantinides

Panayiotis P. ConstantinidesThe currently available list of excipients in the market is unending. They include diverse classes of small molecules and macromolecules of natural or semi-synthetic origin, and they represent all states of matter—gases, liquids, semi-solids, and solids. Excipients are essential ingredients in drug products independent of the route of administration. New use(s) of an approved excipient or the development of novel excipients are driven by scientific and business decisions to address unmet medical need(s), including the essential need for excipients in drug products, patent protection, and revenues.

Traditionally excipients are used as drug solvents and stabilizers, lubricants, glidants, emulsifiers, fillers, preservatives, etc. as described by Rowe, C.R., Sheskey, P.J. and Quinn, M.E in the Handbook of Pharmaceutical Excipients,. Beyond their traditional use as “inactive/inert” 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). For 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. Excipients exhibiting in vitro/in vivo biological activity include lipids (oils, surfactants, fatty acids/esters), polymers (poloxamers, polyethylene glycols, amphiphilic block copolymers), hydrocolloids, minerals (calcium carbonate/phosphate/sulfate, silicates), etc.

So how does a scientist make the best choice? We need an Excipient Classification System (ECS) in order to guide pharmaceutical scientists in the selection of biologically active excipients from the larger pool of excipients, whether the scientists are working with new uses of existing excipients or the development of novel excipients.

This ECS system, plus other excipient characteristics, examples, and uses in oral drug products, was reported in the AAPS Open commentary Considerations and Recommendations on Traditional and Non-Traditional uses of Excipients in Oral Drug Products, which was published online in May. The proposed ECS incorporates the following three classes based on the three primary application areas and uses of excipients in oral drug products: ECS1 (formulation and manufacturing aids); ECS2 (modulators of the PK/PD of the co-formulated drugs); and ECS3 (atypical active pharmaceutical ingredients). Successful implementation and broader acceptance of an ECS requires input and ownership from all major stakeholders, that is, the excipient manufacturers, the end users in the biotech, pharmaceutical, and nutraceutical industries, regulatory agencies, and excipient advocacy groups such as the International Pharmaceutical Excipients Council (IPEC).

Other benefits of ECS would include: a) helping both established and new researchers to clearly understand the role of excipients and assisting in their judicious selection and interpretation of the effect of formulation variables on the in vivo performance of the drug product; b) setting regulatory standards and introducing appropriate guidelines to control within required limits or allowing minimum variation in use of such excipients in post-approval cases, plus recommending submission of adequate information/data related to their use in new drug products; and c) facilitating the qualification and approval process of novel excipients.

Whether you are a new or experienced user of excipients, work directly or indirectly with excipients, let’s open the dialogue. Express your views on the need for an ECS. It is only upon a constructive dialogue and input from stakeholders like you that an appropriate ECS can become a reality.

Panayiotis P. Constantinides, Ph.D., is the founder and president of Biopharmaceutical & Drug Delivery Consulting LLC, Gurnee, Illinois, and affiliated professor of Biopharmaceutical Sciences at Roosevelt University, College of Pharmacy, Schaumburg, Illinois.