A classical pharmaceutical formulation consists of an active pharmaceutical ingredient as well as a number of non-active ingredients. The active pharmaceutical ingredient is considered to be the main medicine component in the formulation which is responsible for the therapeutic effect. The non-active ingredients, also known as excipients, are added to the active pharmaceutical ingredient for a variety of applications including, but not limited to, dilution, solubility, compression, flow aid, improving stability and enhancing color and flavor. These pharmaceutical excipients are considered inert in nature, and are believed not to interfere with the normal functioning of the active pharmaceutical ingredient. However, there are many exceptions to this generalized notion as some excipients have been shown to affect the action of the active ingredient.
Modern day research has shown that excipients have the capacity to either enhance or reduce the effect of an active ingredient. For example, talinolol is a beta blocker medicine which is generally used for high blood pressure and other heart-related diseases. If this drug is formulated with tocopheryl polyethylene glycol succinate (TPGS), its bioavailability has been shown to increase, whereas, when formulated with the poloxamer 188, its bioavailability has been shown to decrease. Furthermore, this effect is seen at a very low concentration and such ingredients are sensitive to concentration. That means that a little change in the concentration of the excipient can lead to drastic changes in the availability of the active ingredient. Increasing the amount of TPGS from 0.005% to 0.01%, for example, can decrease permeability as much as three times [1]. Thus, such excipients have some activity and are not just simply inert!
This has been noticed in already marketed formulations as well. Agenerase is an anti-HIV medicine developed by Glaxo Welcome containing the protease inhibitor, amprenavir, as the active ingredient with propylene glycol as the excipient. The company discovered that the high amount of propylene glycol added to improve the solubilty of amprenavir posed serious health concerns and told medical practitioners to give Agenerase only when no other option was present [2].
In conclusion, research shows that some excipients have the capacity to either improve or reduce the effect of an active ingredient. Therefore, a wise decision is needed to carefully select only those that are necessary for formulating a medication in the most favorable manner possible.
References:
[1] Clinical Pharmacology & Therapeutics (2005) 77, 24.
[2] The Pharmaceutical Journal May (2000), 264, 685.
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