Issue link: https://www.e-digitaleditions.com/i/1087673
12 March 2019 Tablets & Capsules incentives to companies for carrying out specific research and development of drugs for children. Regulators also design requirements to ensure that products are available for infants and children in different age groups and that the products have an acceptable risk-benefit profile. Overcoming pediatric development challenges For companies that want to begin developing pediatric SODFs, outsourcing and collaborating with experts who are experienced in this area offers an obvious advantage. There is no single solution for successful pediatric formu- lation, so having access to a broad range of expertise and drug development technologies can help companies overcome the numerous challenges they'll face and shorten the development process, bringing successful products to patients faster and with reduced costs. For children that are old enough to swallow them, tablets or capsules may be a g o o d o p t i o n , b u t f o r babies and other patients who are unable or unwill- ing to swallow a full-sized tablet or capsule, formula- tions involving multi-par- ticulates or granules may help to improve adherence. For toddlers, mini-tablets are becoming a more popular delivery method, as clinical trials have shown that chil- dren as young as 2 years old can swallow multiple mini-tablets suspended in a spoonful of fruit-flavored jelly. Research and trials have also shown that mini-tablets can be more successful for newborn babies than syrups. Chewable and orally disintegrating products remove the challenge of swallowing altogether. Developers must formulate these dosage forms, as well as those that contain multi-particulates or granules, to include taste-masking agents to ensure patient compliance. Children are less likely than adults to accept a bit- ter-tasting medicine, so no matter how effective a pedi- atric drug is, the dosage form is impractical if the child refuses to take it because of its taste. Taste-masking techniques are wide ranging, from simply adding that the product be an appropriate size for a child to swallow safely. If a tablet or capsule is too large, the child could choke on it, and if it's too small, the child could aspirate the product into her lungs. Obviously, both of these situations are potentially very dangerous. Children can differ greatly physically and physiologi- cally from one another, even when their ages are similar. Drug permeation through the epithelial layer of the gas- trointestinal tract is usually lower for children than for adults but may vary from one active pharmaceutical ingredient (API) to another, so developers must investi- gate this effect on a case-by-case basis. Plasma protein binding, metabolic enzymes, and total body water also vary as a person grows and matures, and there will be dif- ferences in the first-pass effect and glomerular filtration as well as in both renal secretion and absorption. Furthermore, because a child's organ systems are still developing, a number of excipients that are acceptable for adult use are inappropri- ate for pediatric medicines. To overcome the issue of dose variation, developers have used liquid oral formu- lations, allowing practi- tioners to tailor individual doses to patients. However, liquid formulations can introduce different challenges, such as a greater risk of microbial contamination and difficulties with maintain- ing the formulation's physical and chemical stability. Pediatric SODF challenges For drug developers looking to bring new medicines to the market, SODFs are generally seen as the pre- ferred option; but for pediatric medicines, SODFs may be the most challenging. Not only must you create a range of different doses and formulations in a variety of dosage forms, but you also must consider commercial and potential future profit implications, especially in the case of rare or orphan diseases with relatively small patient populations. A further complication is that no standardized tech- niques to assess pediatric SODF product quality cur- rently exist, which makes identifying an effective for- mulation complex and slow. The danger of this is that, if studies become protracted and iterative, costs in both time and money can increase, and the outcome could be an expensive, sub-optimal product. Companies must evaluate this balance of risk and potential reward— especially in a limited-population market—when plan- ning a development program. It's important to note that regulatory authorities under- stand these commercial realities well, and the pharmaceu- tical industry uses regulatory frameworks to make business decisions regarding pediatric clinical trials. Regulatory authorities have revised their recommendations and guide- lines many times, both to clarify guidance and to offer Photo 1: For babies and other patients who are unable or unwilling to swallow a full-sized tablet or capsule, formulations involving multi-particulates or granules may help to improve adherence. For companies that want to begin developing pediatric SODFs, outsourcing and collaborating with experts who are experienced in this area offers an obvious advantage.