Application of in vitro biopharmaceutical methods in development of immediate release oral dosage forms intended for paediatric patients

Manipulating tablets and capsules given to hospitalised children in Norway is common practice

“…As only a few of the active pharmaceutical ingredients covered by this study (Table 3), like azathioprine (class IV) and omeprazole magnesium (class II), belong to one of the critical BCS classes, this could indicate that manipulation might have been of less concern (22,23). However, it should be noted that the BCS classifications are based on adult physiology and will not necessarily be representative of the paediatric population (24,25). As seen from Table 3, eight of the 18 most frequently administered active pharmaceutical ingredients were practically insoluble in water (1:>10 000) or only very slightly soluble (1:1000-10 000).…”

Understanding peroral absorption: regulatory aspects and contemporary approaches to tackling solubility and permeability hurdles

“…The BCS solubility definition includes the highest dose strength in volume of 250 mL where dose/solubility (D:S)<250 refers highly soluble drugs but cannot be extended to pediatric patients as the volume does not hold true. Attempts are being carried out to extend the BCS to pediatric BCS 55 . Various solubility determination methods have been developed to assess solubility at various stages of drug discovery and development.…”

On the BCS biowaivers of orally disintegrating tablets

“…The authors appear to have ignored the effect that ODT are usually administered without a glass of water and this is an important consideration from the biowaiver perspective. As this is the case for ODT, the solubility classification should not be based on 250 mL just as, for example, in paediatric BCS (Abdel-Rahman et al, 2012;Batchelor et al, 2013). In addition, it is not clear if the studies where the ODT and the other conventional immediate release dosage form demonstrated bioequivalence were conducted with or without water for the ODT.…”