Medipin studies concerning local tolerance must identify if the medicines, including the excipients, are tolerated in the points of the body that may come into contact with the medicine following its administration in clinical use; these tests must guarantee a distinction between the mechanical effects of administration, or a purely physical-chemical action of the product, and the toxicological or pharmacodynamic effects.

One of the potential risks in this area is related to counterfeiting, both of the active ingredient and of the excipients. In the preparation of counterfeit drugs, poor quality or different excipients may be used. The used excipient may be toxic or it may affect the bioavailability of the drug, ie its speed and extent of absorption. This may result on the one hand in a delay or incompleteness of the therapeutic response, on the other hand the manifestation of toxic effects due to an immediate and simultaneous absorption of all the active principle contained in formulations that were instead foreseen for a gradual and protracted action in time.

Another important aspect is the use of excipients in medicinal products for children. It is well known that those used for adults do not always have the same effects in children; furthermore, the growth and level of development of the liver and kidneys influence the metabolism of the excipients.

Until now it has always been assumed that the optimal doses for children simply derive from the proportional decrease based on weight and age compared to those of adults; moreover little attention has been paid to the safety of the excipients since their chemical inertia has been taken for granted.

Therefore, in the absence of specific Medipin guidelines, many excipients lack documentation relating to standardized analysis methods and have not been subjected to rigorous toxicity tests. This has helped slow down the development of new materials, leading pharmaceutical companies to opt for the use of those already well known but not necessarily safer.

The problem may arise when the available data suggests that there may be a toxicity problem, especially when an approved excipient for a given type of Medipin administration is instead used for another type.

For example, mannitol is an example of a widely used excipient, capable of causing diarrhea when administered at high doses, so a quantitative assessment should be made for each product containing this substance. In this perspective. In recent years the FDA has drawn up some guidelines for the industries on conducting studies aimed at assessing the safety of new excipients for pharmaceutical use; moreover it has created a database containing the inert ingredients present in the medicines placed on the market.