The release and absorption profile of an oral medication is influenced by the physicochemical properties of the drug and its formulation, as well as by the anatomy and physiology of the gastrointestinal (GI) tract. During drug development the bioavailability of a new drug is typically assessed in early clinical studies in a healthy adult population. However, many disease conditions are associated with an alteration of the anatomy and/or physiology of the GI tract. The same holds true for some subpopulations, such as paediatric or elderly patients, or populations with different ethnicity. The variation in GI tract conditions compared to healthy adults can directly affect the kinetics of drug absorption, and thus, safety and efficacy of an oral medication. This review provides an overview of GI tract properties in special populations compared to healthy adults and discusses how drug absorption is affected by these conditions. Particular focus is directed towards non-disease dependent conditions (age, sex, ethnicity, genetic factors, obesity, pregnancy), GI diseases (ulcerative colitis and Crohn's disease, celiac disease, cancer in the GI tract, Roux-en-Y gastric bypass, lactose intolerance, Helicobacter pylori infection, and infectious diseases of the GI tract), as well as systemic diseases that change the GI tract conditions (cystic fibrosis, diabetes, Parkinson's disease, HIV enteropathy, and critical illness). The current knowledge about GI conditions in special populations and their impact on drug absorption is still limited. Further research is required to improve confidence in pharmacokinetic predictions and dosing recommendations in the targeted patient population, and thus to ensure safe and effective drug therapies.

A meeting that was organized by the Academy of Pharmaceutical Sciences Biopharmaceutics and Regulatory Sciences focus groups focused on the challenges of Developing Clinically Relevant Dissolution Specifications (CRDS) for Oral Drug Products. Industrial Scientists that were involved in product development shared their experiences with in vitro dissolution and in silico modeling approaches to establish clinically relevant dissolution specifications. The regulators shared their perspectives on the acceptability of these different strategies for the development of acceptable specifications. The meeting also reviewed several collaborative initiatives that were relevant to regulatory biopharmaceutics. Following the scientific presentations, a roundtable session provided an opportunity for delegates to discuss the information that was shared during the presentations, debate key questions, and propose strategies to make progress in this critical area of regulatory biopharmaceutics. It was evident from the presentations and subsequent discussions that progress continues to be made with approaches to establish robust CRDS. Further dialogue between industry and regulatory agencies greatly assisted future developments and key areas for focused discussions on CRDS were identified.

Medicine co-administration with food or drink vehicles is a common administration practice in paediatrics. The aims of this review were (i) to describe the current recommended strategies for co-administration of paediatric medicines with food and drinks (vehicles); (ii) to compare current administration recommendations from different countries; and (iii) to obtain a global perspective on the rationale behind the choice of recommended vehicle, in the context of the physicochemical properties of the drug and formulation. This study used a defined search strategy on the practices of paediatric medicine co-administration with vehicles, recommended in a commonly used paediatric and neonatal handbook, in addition to the information previously gathered from UK formularies. Logistic regression analysis was performed to further understand the biopharmaceutical basis of the choice of recommended vehicle for medicine co-administration. Differences were identified in the type of vehicles globally recommended for medicine co-administration. Ultimately, a statistical model was developed which provided an understanding on which vehicle is recommended for use with drugs/formulations, with basis on their biopharmaceutical properties. Overall, this review highlights the areas where further information is needed to support standardised procedures and guide the recommendation of age-appropriate and acceptable vehicles for use in the co-administration of paediatric medicines. Unified requirements are needed for harmonisation of the practice of medicine co-administration with vehicles. In vitro and/or in silico tools should be developed to evaluate the potential clinical outcomes of this practice during paediatric drug development.

A webinar series that was organised by the Academy of Pharmaceutical Sciences Biopharmaceutics focus group in 2021 focused on the challenges of developing clinically relevant dissolution specifications (CRDSs) for oral drug products. Industrial scientists, together with regulatory and academic scientists, came together through a series of six webinars, to discuss progress in the field, emerging trends, and areas for continued collaboration and harmonisation. Each webinar also hosted a Q&A session where participants could discuss the shared topic and information. Although it was clear from the presentations and Q&A sessions that we continue to make progress in the field of CRDSs and the utility/success of PBBM, there is also a need to continue the momentum and dialogue between the industry and regulators. Five key areas were identified which require further discussion and harmonisation.