Manipulation of oral medication was regularly performed on paediatric wards. There is an urgent need for age-appropriate medicines, documented and standardised processes for manipulating medicines and staff training on the consequences of manipulation.

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forms (eg, tablets) may be manipulated by, for instance, splitting, crushing or dispersing, before a small fraction is withdrawn to obtain a prescribed dose.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precision that can be encountered when aspirin tablets are dispersed and a fraction (10% or 20% of the whole tablet) is withdrawn as a paediatric dose is illustrated for four different commercially available aspirin tablets (one conventional, one chewable and two dispersible) and three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...

Intravitreal injections of antibody-based biologics targeting vascular endothelial growth factor (VEGF) are highly effective and have markedly decreased the risk of visual impairment associated with prevalent retinal diseases, such as neovascular age-related macular degeneration and diabetes macular oedema. The diseases are chronic in their nature, and most patients need long-term therapy to suppress disease activity. We previously reported a compounding method for repackaging and storage of aflibercept (Eylea), a commonly used anti-VEGF biologic, in silicone oil-coated plastic syringes without compromising drug stability or activity. In addition to improving safety and time spent per patient, compounding of anti-VEGF biologics enables single-dose vials to be split into multiple syringes, thereby considerably reducing waste and drug expenses. However, symptomatic silicone oil droplets may deposit in the eye’s vitreous body after repetitive injections. To fully avoid this complication, we here report on a novel pharmaceutical compounding method using silicone oil-free syringes and a 33 G × 9 mm Low Dead Space Needle hub injection needle. We evaluate the method for three anti-VEGF biologics commonly used in ophthalmology: aflibercept, ranibizumab (Lucentis) and bevacizumab (Avastin). Our results show that compounding and storage for one week does not compromise the functional activity of the biologics and allows for safe and cost-effective compounding of anti-VEGF biologics for intravitreal injections in prefilled silicone oil-free syringes.

The triple-component epidural analgesic solution remained stable during six months of cold storage, followed by four days of storage at room temperature. No significant degradation of adrenaline was observed in infusion solutions returned from the wards.

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