What is already known on this subject ► Children lack age-appropriate medicines, and because of this dosage forms (eg, tablets) may be manipulated by, for instance, splitting, crushing or dispersing, before a small fraction is withdrawn to obtain a prescribed dose. ► MODRIC (Manipulation of Drugs Required in Children) has provided guidelines for manipulation of tablets, and the guideline recommends that dispersion should only be performed if there is knowledge about 'solubility', 'dispersibility' or 'any special characteristics of the formulation'. ► A previous study found that manipulation through dispersion and fraction extraction of tablets containing the slightly soluble substance aspirin did not result in correct doses 22 ; however, only one tablet formulation was investigated. What this study adds ► The variation in dose accuracy and dose precision that can be encountered when aspirin tablets are dispersed and a fraction (10% or 20% of the whole tablet) is withdrawn as a paediatric dose is illustrated for four different commercially available aspirin tablets (one conventional, one chewable and two dispersible) and three different mixing procedures. ► The dose accuracy varied markedly for the different kinds of tablets, and only fractions taken from the dispersible aspirin tablets came within 20% of the intended dose. ► Fractions taken from dispersions of the conventional and chewable tablets did not reach this level of accuracy, regardless of mixing procedure. AbsTrACT Objectives When caring for children in a hospital setting, tablets are often manipulated at the ward to obtain the right dose. One example is manipulation of tablets containing the slightly water-soluble substance aspirin, used in paediatric care as an antiplatelet agent. The evidence base, however, for choosing certain tablet formulations and manipulation methods over others for extraction of proportions is lacking. The aim of this study was to investigate the effect of tablet formulation and manipulation technique on the dose accuracy and precision attained when dispersing different commercially available aspirin tablets and extracting a small proportion suitable for children. Methods The manipulation methods investigated simulated those observed in the paediatric clinic. Four tablet formulations-one chewable, one conventional and two dispersible-were dispersed in 10 mL water in a medicine measure. On (1) passive dispersion, (2) mixing by stirring with the syringe, or (3) stirring and pumping the dispersion in and out of the syringe, respectively, proportions (1 mL or 2 mL) were extracted and the doses recovered were determined using a validated UHPLC (ultra high-pressure liquid chromatography) method. results Fractions from the four different dispersed aspirin tablet formulations varied from 99% to 3% of that intended with the lowest degree of mixing, and from 96% to 34% of that intended with the highest degree of mixing. Only the dispersible tablets gave average doses within 20% of the intended dose. Conclusions Fraction extraction from d...

When caring for children in the clinic, it is frequently a practical problem that age-appropriate dosage forms are lacking. This has been a topic of concern for a considerable time. 1-3 To find practical solutions in this situation, drugs approved for use in the adult population are sometimes used off-label. 3,4 Manipulation of drug form (eg splitting and crushing tablets, opening capsules, dispersing the resulting powders) is one type of such off-label handling. 5,6 A recent study demonstrated that in 17% of all administrations to children, drug form is manipulated outside what is described in the Summary of Product Characteristics (SmPC) prior to administration. 7 Although the manipulation is performed to achieve an accurate dose for the individual child, the actual dose obtained is often