DRUG DELIVERY SUPPLEMENT
Child’s play Dr Anthony Qu, vice president of scientific affairs at Cambrex and Dr Yanjun Zhao, market intelligence manager examine the complexities of developing oral doses for the paediatric market.
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nfants, children and adolescents require different oral dosage forms depending on their swallowing abilities, taste preferences and dosage requirements. The development of tailored solutions that are practical to manufacture increases medication adherence and provides a competitive advantage.
children, but traditional capsules and tablets work as well, as do liquid dosage forms. Adolescents prefer capsules, chewable tablets and mini tabs. For all children, the palatability of medication can have a direct impact on treatment success. For many younger children, easy-to-swallow formulations are equally necessary.
GROWING PAEDIATRIC MARKET Currently there are nearly 1,300 paediatric clinical trials underway investigating the safety and efficacy of over 600 drug substances for the treatment of various cancers, central nervous system disorders, infectious diseases and other ailments.
CHOOSING THE RIGHT DOSAGE FORM Once the age-appropriate dosage form options are identified, the next step is to determine the most appropriate dosage form for the specific API in question. The first consideration is whether a measurable dosage form is required, such as dosing based on milligram (mg) of drug per kilogram (kg) of body weight. If yes, then liquid formulation will be suitable. Tablets and capsules would not be suitable in this case. Next, it is important to consider whether taste masking is needed and effective in the drug products. If it is not effective, then sprinkle powders or granules, tablets or capsules are the best choice because taste masking can be effective and achieved via coating technology in solid dosage forms. For liquid formulations, drug products must be chemically stable over a two-year period.
In the US, paediatric drugs based on new molecular entities (NMEs) must be evaluated in paediatric clinical trials. Existing drugs marketed for adults only can, if proven safe and effective for children, receive approval from the FDA as paediatric medications with six months of marketing exclusivity. Similarly, existing drugs proven safe and effective as paediatric medications for different indications can also benefit from marketing exclusivity. NEED FOR AGE-APPROPRIATE DOSAGE FORMS Consequently, developing paediatric dosage forms for both new and existing drug substances provides an effective means for expanding market reach and improving the lifecycle management of many different products. The paediatric population includes children ranging from infants to teenagers, and each age subgroup has different pharmacokinetic responses, dosage requirements, swallowing abilities and taste preferences. Therefore ageappropriate formulations are essential. Liquids are ideal for newborns, infants and toddlers. They are also effective for pre-school children, along with mini-tablets. Chewable tablets may be the best solution for school
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FORMULATION DESIGN REQUIREMENTS Overall design requirements for paediatric oral dosage forms are primarily based on the age, body size and swallowing ability of the target population. In addition to liquid and solid forms such as tablets and capsules, multiparticulate formulations like granules and mini-tabs, and alternative oral delivery pathways such as dose-sipping technology are available. Liquid dosage forms are ideal for patients with trouble swallowing, allow for flexible dosing and are more rapidly absorbed than solid dosage forms, but they often have shorter expiration periods; require special storage conditions (i.e., refrigeration); require careful dosage measurement; have unpleasant tastes and can be difficult to administer.