Perspective
Paediatric pharmacology: Remember the excipients

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Abstract

Excipients are largely used by pharmaceutical industry to guarantee preservation and stability and confer shape, volume and consistency to pharmaceutical preparations. They are particularly important in medicines intended for prescription in children since they often play a critical role in manufacturing of suitable paediatric formulations. It was generally believed that excipients were inert substances; on the contrary, it is actually well known that excipients are far from being inactive and much more interest is growing about safety issues associated with their extensive use by pharmaceutical industry in general, and for manufacturing of paediatric drugs in particular.

Introduction

“Excipere” is a latin origin word whose meaning was “to mix” or “to gather”. Historically, the word excipient has been used to define a substance which works as a medium for administering drugs or an inert agent capable of conferring a suitable consistency or form to a drug. More recently, the word excipient was defined by the United States’ National Formulary as “everything in the formulation except than the active drug” [1]. Excipients exist in mostly all drugs as diluents, fillers, solvents, emulsifiers, binders, lubricants, glidants, disintegrants, sweeteners, preservatives and stabilising, flavouring or colouring agents. They play a critical role in conferring shape, volume and consistency to the pharmaceutical preparation thus ensuring the easiest administration to the target population; in delivering the active substance to its proper anatomical site of action and enabling its bioavailability; in assuring stability and preservation of the drug; and in favouring compliance by improving drug taste and aroma.

Because of their lack of pharmacological action, excipients have always been considered inert agents and, for this reason, their importance has been largely underestimated. The assumption that excipients are inactive is rapidly going to fade and, on the contrary, they are recently attracting more interest particularly because of safety concerns. Excipients have in fact been associated with specific toxicity issues and with allergic reactions and intolerances. Furthermore, it has been observed the existence of possible pharmacological interactions between excipients and active principles, which may occur secondary to chemical and/or physical transformations. Some excipients (polyethyleneglycol, sodium pyrophosphate, mannitol) can in fact accelerate the passage of oral administered active substances through the intestinal tract thus resulting in diminished absorption of the active principle. Another example of interaction may occur between the carbonilic groups of an excipient like polyvinylpyrrolidone, and preparations containing donor groups of hydrogen, like famotidine and atenolol, which can cause problems of incompatibility.

Bioavailability of a drug can diminish because excipients and active agents bind to form insoluble complexes whit a consequent reduction of the mucosal absorption [2].

Section snippets

Paediatric issues with common excipients in medicinal products

Paediatric pharmacology has always represented a particular research field not only for study and development of active principles but also as regard excipients. The development of paediatric feasible formulations can in fact represent a challenge for the pharmaceutical industry. Children are not “small adults” but are instead characterized by unique needs. A drug should have a good taste and mouth feel in order to enhance palatability of oral liquid, chewable or dispersible preparations;

Conclusion

Pharmaceutical manufacturers in Europe should respect actual regulations by European Medicines Agency (EMEA) for marketing a new medicinal product [23]. Every excipient should by easily recognized by indication of fundamental information about the producer, the quality, stability and purity of the product and about results of microbiological and toxicological tests. The addition of every single excipient should be justified as regard both its function and amount in the medicinal product,

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