Biopharmaceutical considerations in paediatrics with a view to the evaluation of orally administered drug products – a PEARRL review (original) (raw)
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Food effects in paediatric medicines development for products Co-administered with food
International journal of pharmaceutics, 2017
A small amount of food is commonly used to aid administration of medicines to children to improve palatability and/or swallowability. However the impact of this co-administered food on the absorption and subsequent pharmacokinetic profile of the drug is unknown. Existing information on food effects is limited to standard protocols used to evaluate the impact of a high fat meal in an adult population using the adult medication. In the absence of a substantial body of data, there are no specific guidelines available during development of paediatric products relating to low volumes of potentially low calorie food. This paper brings together expertise to consider how the impact of co-administered food can be risk assessed during the development of a paediatric medicine. Two case studies were used to facilitate discussions and seek out commonalities in risk assessing paediatric products; these case studies used model drugs that differed in their solubility, a poorly soluble drug that dem...
Biopharmaceutics & drug disposition, 2016
The dissolution, intestinal absorption and presystemic metabolism of a drug depend on its physicochemical characteristics but also on numerous physiological (e.g. gastrointestinal pH, volume, transit time, morphology) and biochemical factors (e.g. luminal enzymes and flora, intestinal wall enzymes and transporters). Over the last decade, evidence has accumulated indicating that these factors may differ in children and adults resulting in age-related changes in drug exposure and drug response. Thus, drug dosage may require adjustment for the pediatric population to ensure the desired therapeutic outcome and to avoid side-effects. Although tremendous progress has been made in the understanding the effects of age on intestinal physiology and function, significant knowledge gaps remain. Studying and predicting pharmacokinetics in pediatric patients remains challenging due to ethical concerns associated with clinical trials in this vulnerable population, and because of the paucity of pre...
Size and Taste Matters: Recent Progress in the Development of Age-Appropriate Medicines for Children
Pharmaceutical Medicine, 2017
Drug therapy for children is one of the cornerstone developments that have sharply reduced childhood mortality. Despite this, many challenges remain in ensuring that children receive safe and effective drug therapy. There are unique issues in treating children with oral medication relating to development, existing formulations and medication acceptability. Medication acceptability in children is complex relating to a wide range of factors, including drug palatability. Over the past decade there has been an increasing interest in and research as to how to improve and enhance child-specific drug formulations including the development of specific instruments for assessing drug palatability in children and new approaches to teaching medication literacy to families. Approaches to enhancing drug acceptability have also included organoleptic (taste masking) strategies as well as the creation of a number of innovative taste-blocking strategies and new technologies for formulation preparation. Polymer coating, microencapsulation and heat melt technologies have resulted in drug formulations that are now being assessed in children while soft melt and gel formulations are now commonly used. Mini-tablets offer the potential of using solid delivery systems in even very young infants. This work has resulted in a number of highly promising developments that are being evaluated for clinical use as well as providing insights into new directions in pursuit of the common goal of effective and safe drug therapy for children. Ongoing challenges include the need for drug regulatory agencies to work closely with drug regulatory agencies in facilitating innovation in formulation design and approval.
AAPS PharmSciTech, 2016
The European Paediatric Formulation Initiative (EuPFI), founded in 2007, aims to promote and facilitate the preparation of better and safe medicines for children through linking research, and information dissemination. It brings together the capabilities of industry, academics, hospitals and regulators within a common platform in order to scope the solid understanding of the major issues, which will underpin the progress towards the future of paediatric medicines we want. The EuPFI was formed in parallel to the adoption of regulations within the EU and USA and has served as a community that drives research and dissemination through publications and the organisation of annual conferences. The membership and reach of this group has grown since its inception in 2007 and continues to develop and evolve to meet the continuing needs and ambitions of research into and development of age appropriate medicines. Five diverse workstreams (Age-appropriate medicines, Biopharmaceutics, Administration Devices, Excipients and Taste Assessment & Taste Masking (TATM)) direct specific workpackages on behalf of the EuPFI. Furthermore EuPFI interacts with multiple diverse professional groups across the globe to ensure efficient working in the area of paediatric medicines. Strong commitment and active involvement of all EuPFI stakeholders has proved to be vital to effectively address knowledge gaps related to paediatric medicines, discuss potential areas for further Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation research and identify issues that need more attention and analysis in the future.
British Journal of Clinical Pharmacology, 2021
Improved global access to novel age-appropriate formulations for paediatric subsets, either of new chemical entities or existing drugs, is a priority to ensure that medicines meet the needs of these patients. However, despite regulatory incentives, the introduction to the market of paediatric formulations still lags behind adult products. This is mainly caused by additional complexities associated with the development of acceptable age-appropriate paediatric medicines. This position paper recommends the use of a paediatric Quality Target Product Profile (pQTPP) as an efficient tool to facilitate early planning and decision making across all teams involved in paediatric formulation development during the children-centric formulation design for new chemical entities, or to repurpose/reformulate off-patent drugs. Essential key attributes of a paediatric formulation are suggested and described. Moreover, greater collaboration between formulation experts and clinical colleagues, including healthcare professionals, is advocated to lead to safe and effective, age-appropriate medicinal products. Acceptability testing should be a secondary endpoint in paediatric clinical trials to ensure postmarketing adherence is not compromised by a lack of acceptability. Not knowing the indications and the related age groups and potential dosing regimens early enough is still a major hurdle for efficient paediatric formulation development; however the proposed pQTPP could be a valuable collaborative tool for planning and decision making to expedite paediatric product development, particularly for those with limited experience in developing a paediatric product. The need to improve the availability of age-appropriate paediatric formulations for all children is a priority, for both new chemical entities and existing drug products that require reformulating/repurposing to ensure that medicines meet the neglected needs of the patients. Identification of key attributes to be considered for inclusion in a proposed paediatric Quality Target Product Profile (pQTPP). This provides a useful tool for planning and decision making during the development of paediatric formulations for both new chemical entities and off-patent drugs.
Pediatric drugsa review of commercially available oral formulations
Journal of pharmaceutical …, 2008
Pediatric oral formulations can be quite scientifically challenging to develop and the prerequisites for both a measurable dosage form to administer based upon bodyweight, and also taste-masking are two of the challenges unique for pediatric oral formulations. The physicochemical and organoleptic properties of the active drug substance such as solubility, chemical stability, and taste along with the intended dose can determine which formulations are feasible to develop. Oral pediatric formulations are available in 17 different varieties and can be either a ready-to-use formulation such as a solution, syrup, suspension, tablet, scored tablet, chewable tablet, orally disintegrating tablet, or thin strip, or can also be a formulation that requires manipulation such as a powder for constitution to a suspension, tablet for constitution to a suspension, powder for constitution to a solution, drops for reconstitution to a suspension, concentrated solution for dilution, effervescent tablet, bulk oral granules, bulk oral powder, or solid in a capsule to mix with food or drink. Recently there has been an increase in pediatric formulation development inspired by increased regulatory incentives. The intent of this review is to educate the reader on the various types of formulations administered orally to pediatrics, the rationale in deciding which type of formulation to develop, the excipients used, development challenges, the in-use handling of oral pediatric formulations, and the regulatory incentives.