Oral biopharmaceutics tools: recent progress from partnership through the Pharmaceutical Education and Research with Regulatory Links collaboration
| Autor: | Laura J. Henze, Christos Reppas, Jennifer B. Dressman, Marina Statelova, Chara Litou, Christina Pentafragka, Patrick J O'Dwyer, Karl J. Box, Brendan T. Griffin, Maria Vertzoni |
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| Přispěvatelé: | Publica |
| Rok vydání: | 2021 |
| Předmět: |
Drug
Physiologically based pharmacokinetic modelling Swine Computer science Drug Compounding Food Effect Study media_common.quotation_subject Pharmaceutical Research Administration Oral Biological Availability Pharmaceutical Science 02 engineering and technology Models Biological 030226 pharmacology & pharmacy Biopharmaceutics Bio-enabling drug products Food-Drug Interactions 03 medical and health sciences 0302 clinical medicine Drug Development Pharmacokinetics Animals Humans Intersectoral Collaboration media_common Pharmacology Paediatrics Pig model Food effect 021001 nanoscience & nanotechnology Bioavailability Gastrointestinal Tract In vitro testing Education Pharmacy PBPK modelling Biorelevant Biochemical engineering 0210 nano-technology Oral retinoid |
| Zdroj: | Journal of Pharmacy and Pharmacology. 73:437-446 |
| ISSN: | 2042-7158 0022-3573 |
| DOI: | 10.1093/jpp/rgaa055 |
| Popis: | ObjectivesTo summarise key contributions of the Pharmaceutical Education and Research with Regulatory Links (PEARRL) project (2016–2020) to the optimisation of existing and the development of new biopharmaceutics tools for evaluating the in vivo performance of oral drug products during the development of new drugs and at the regulatory level.Key findingsOptimised biopharmaceutics tools: Based on new clinical data, the composition of biorelevant media for simulating the fed state conditions in the stomach was simplified. Strategies on how to incorporate biorelevant in vitro data of bio-enabling drug products into physiologically based pharmacokinetic (PBPK) modelling were proposed. Novel in vitro biopharmaceutics tools: Small-scale two-stage biphasic dissolution and dissolution-permeation setups were developed to facilitate understanding of the supersaturation effects and precipitation risks of orally administered drugs. A porcine fasted state simulated intestinal fluid was developed to improve predictions and interpretation of preclinical results using in vitro dissolution studies. Based on new clinical data, recommendations on the design of in vitro methodologies for evaluating the GI drug transfer process in the fed state were suggested. The optimized design of in vivo studies for investigating food effects: A food effect study protocol in the pig model was established which successfully predicted the food-dependent bioavailability of two model compounds. The effect of simulated infant fed state conditions in healthy adults on the oral absorption of model drugs was evaluated versus the fasted state and the fed state conditions, as defined by regulatory agencies for adults. Using PBPK modelling, the extrapolated fasted and infant fed conditions data appeared to be more useful to describe early drug exposure in infants, while extrapolation of data collected under fed state conditions, as defined by regulators for adults, failed to capture in vivo infant drug absorption.SummarySubstantial progress has been made in developing an advanced suite of biopharmaceutics tools for streamlining drug formulation screening and supporting regulatory applications. These advances in biopharmaceutics were achieved through networking opportunities and research collaborations provided under the H2020 funded PEARRL project. |
| Databáze: | OpenAIRE |
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