Article
Pharmacology & Pharmacy
Mariana Guimaraes, Pascal Somville, Maria Vertzoni, Nikoletta Fotaki
Summary: This study explores the potential of biopharmaceutics in vitro tools to predict drug performance in children. Age-appropriate dissolution studies were conducted using biorelevant set-ups to mimic gastrointestinal conditions. The study demonstrates the value of age-appropriate biorelevant dissolution testing in assessing pediatric drug performance.
Article
Pharmacology & Pharmacy
Matthias Van der Veken, Michael Aertsen, Joachim Brouwers, Cordula Stillhart, Neil Parrott, Patrick Augustijns
Summary: This study analyzed clinical MRI data of pediatric patients and found that fluid volumes in the stomach, duodenum, jejunum, and small intestine increase with age. Body height and weight were identified as the best estimators for these fluid volumes, but no method performed ideally.
Article
Pharmacology & Pharmacy
Mariana Guimaraes, Maria Vertzoni, Nikoletta Fotaki
Summary: This study aimed to develop a physiologically based pharmacokinetic (PBPK) model coupled with age-appropriate in vitro dissolution data to describe drug performance in adults and pediatric patients. Through two case studies, the study demonstrated how a PBPK absorption modeling strategy can facilitate decision-making and enhance understanding of drug performance in the pediatric population during drug development.
Article
Chemistry, Medicinal
Atsushi Kambayashi, Jennifer B. Dressman
Summary: The present study aimed to develop a physiologically based biopharmaceutics approach to predict the bioequivalence of dosage forms containing poorly soluble drugs. The variations in gastrointestinal physiological parameters and inter-individual variabilities were considered in in vitro dissolution testing and in silico simulations. The bioequivalence between different formulations was accurately predicted using the proposed approach. Further characterization of gastrointestinal physiological parameters and their variabilities is important for more precise predictions.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Mariana Guimaraes, Anil Maharaj, Andrea Edginton, Maria Vertzoni, Nikoletta Fotaki
Summary: The aim of this study was to investigate the effects of age on drug solubilization and identify drugs at risk of altered drug solubility in newborns and young infants compared to adults. The results showed that the physicochemical properties of drugs and the composition of gastrointestinal fluids played a crucial role in drug solubility differences between different age groups. The use of pediatric biorelevant media can help to identify potential risks of altered drug solubilization in younger patients during drug development.
Article
Pharmacology & Pharmacy
Konstantinos Stamatopoulos, Paola Ferrini, Dung Nguyen, Ying Zhang, James M. Butler, Jon Hall, Nena Mistry
Summary: This study describes a strategy that integrates in vitro solubility and permeability data into a PBBM model to predict the food effect of a BCS IV zwitterionic drug (GSK3640254) observed in clinical studies. The PBBM model was developed and validated using clinical data obtained from healthy volunteers. The results showed that the positive food effect observed in the clinical studies was attributed to micelle-mediated enhanced solubility and permeability. The developed PBBM model accurately predicted the results of the food effect, indicating its effectiveness in predicting the food effect of BCS class IV drugs.
Review
Chemistry, Multidisciplinary
Di Wu, Min Li
Summary: Physiologically based biopharmaceutics modeling (PBBM) integrates physicochemical properties of drugs and formulation characteristics with physiological parameters to predict drug absorption and pharmacokinetics. Despite its wide applications, there are still obstacles to the use of PBBM in drug development.
PHARMACEUTICAL RESEARCH
(2023)
Article
Medicine, Research & Experimental
Ioannis Loisios-Konstantinidis, Jennifer Dressman
Summary: PBPK/PD modeling is widely used to predict in vivo drug performance, but there are challenges with regulatory acceptance, incomplete physiological understanding, and model validation, which can limit their translatability and predictive performance. Advances in GI physiology and mechanistic tools will play a key role in the future development of PBBM.
MOLECULAR PHARMACEUTICS
(2021)
Article
Pharmacology & Pharmacy
Gopal Pawar, Fang Wu, Liang Zhao, Lanyan Fang, Gilbert J. Burckart, Kairui Feng, Youssef M. Mousa, Abdullah Al Shoyaib, Marie-Christine Jones, Hannah K. Batchelor
Summary: This study investigated the impact of gastro-intestinal fluid volume and bile salt concentration on the dissolution of carbamazepine immediate release tablets. The study found that changes in the composition of the biorelevant media had little effect on CBZ dissolution. PBPK modeling showed that 500 mL of Ad-FaSSGF/Ad-FaSSIF media for adults and 200 mL Ped-FaSSGF/FaSSIF media for pediatrics were the most predictive dissolution volumes and media compositions.
Article
Pharmacology & Pharmacy
K. Yuvaneshwari, Sivacharan Kollipara, Tausif Ahmed, Siddharth Chachad
Summary: Physiologically based pharmacokinetic (PBPK) modeling and physiologically based biopharmaceutics modeling (PBBM) are widely used tools in drug discovery and development, with applications in pharmacokinetics prediction, formulation design, and regulatory guidelines. This review provides an overview of the applications of PBPK modeling in generic product development, including case studies and future perspectives.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Dwaipayan Mukherjee, Manoj S. Chiney, Xi Shao, Tzuchi R. Ju, Mohamad Shebley, Patrick Marroum
Summary: The aim of this analysis was to use a physiologically based pharmacokinetic (PBPK) model to predict the impact of changes in dissolution rates on elagolix exposures and define clinically relevant acceptance criteria for dissolution. The model results indicated that a slower dissolution rate would not have a clinically significant impact on elagolix exposures, informing the setting of wider dissolution specifications without requiring in vivo studies.
BIOPHARMACEUTICS & DRUG DISPOSITION
(2022)
Article
Chemistry, Medicinal
Adithya Karthik Bhattiprolu, Sivacharan Kollipara, Tausif Ahmed, Rajkumar Boddu, Siddharth Chachad
Summary: Product DRL is a generic IR tablet formulation with BCS Class-III API, available in two strengths: 50mg & 100mg. The reference and test formulations have shown bioequivalence in vivo for the higher strength. However, when the generic product was introduced to different markets, the reference product from another market exhibited slower dissolution, leading to the inability to waive the bioequivalence study. To address this issue, a Gastroplus (R) PBBM model was developed and validated, and virtual bioequivalence trials were conducted. The results demonstrated that despite the slower dissolution, the test product achieved bioequivalence with the reference product for both strengths.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Review
Chemistry, Multidisciplinary
Om Anand, Xavier J. H. Pepin, Vidula Kolhatkar, Paul Seo
Summary: The use of physiologically based biopharmaceutics modeling (PBBM) to support drug product quality attributes is an evolving field with growing interest. Establishing an in vitro-in vivo link is crucial for achieving patient centric quality standards. While PBBM offers advantages, there are challenges that require further improvements. Collaboration between regulatory, industry, and academic fields can advance the field and deliver on the promises of PBBM in establishing patient centric quality standards.
PHARMACEUTICAL RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Daniel Porat, Oleg Dukhno, Mazal Partook-Maccabi, Ella Vainer, Sandra Cvijic, Arik Dahan
Summary: Gastrointestinal changes after bariatric surgery can affect the solubility and absorption of drugs. Etoricoxib's solubility decreased while etodolac's solubility increased with increasing pH. Etoricoxib's dissolution was hindered while etodolac's dissolution improved post-surgery. Crushing tablets did not improve post-bariatric dissolution. Etoricoxib absorption was significantly impaired post-surgery, while celecoxib and etodolac absorption remained unaffected.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Medicine, Research & Experimental
Bart Hens, Inese Sarcevica, Irena Tomaszewska, Mark Mcallister
Summary: The TIM-1 model is an in vitro gastrointestinal simulator used to evaluate drug release in the body. The digital TIM-1 model has been shown to accurately reflect drug concentrations and bioaccessible fractions under different dietary conditions. Experimental and simulated data also indicate that the absence of stomach acid leads to a decrease in the bioaccessible fraction of drugs.
MOLECULAR PHARMACEUTICS
(2023)
Article
Pharmacology & Pharmacy
Xuezhi Zhuo, Vito Fodera, Per Larsson, Zarah Schaal, Christel A. S. Bergstrom, Korbinian Lobmann, Aleksei Kabedev
Summary: Our previous work demonstrated that beta-lactoglobulin-stabilized amorphous solid dispersion (ASD) loaded with 70 % indomethacin remains stable for over 12 months. We further investigated the stabilization mechanisms by testing five other drug molecules and using experimental techniques and molecular dynamics simulations. The results showed that steric confinement, hydrogen bonding, and the glass transition temperature of the drug molecule play important roles in stabilizing ASDs with high drug loadings.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Sebastian Schmidt, Ulrike Holzgrabe
Summary: The binding of drugs to plasma proteins, such as human serum albumin (HSA), is crucial for determining pharmacokinetic parameters. This study investigated the enantioselective binding of S- and R-ketamine to HSA. It was found that ketamine has weak affinity to HSA, with no significant differences in binding behavior between the individual enantiomers and the racemate. The aromatic ring and N-methyl group were identified as the most strongly involved structural moieties in the binding of ketamine to HSA.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Yuchen Zhao, Han Wang, Lin Jin, Ziwei Zhang, Lianghu Liu, Mengqi Zhou, Xianzheng Zhang, Lingling Zhang
Summary: Interleukins (ILs) are important for communication between immune cells and non-immune cells, but dysregulation of ILs expression is a characteristic of autoinflammatory diseases. Drugs targeting ILs have significant clinical benefits, but may also cause adverse reactions. Fusion protein technology, with its ability to enhance therapeutic efficacy, has been explored for developing anti-inflammatory drugs. This review discusses the efficacy of fusion protein drugs developed with ILs or their receptors in treating autoinflammatory diseases, highlighting the potential of this technology in future anti-inflammatory drug development.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Serena Bertoni, Elena Simone, Stefano Sangiorgi, Beatrice Albertini, Nadia Passerini
Summary: This study investigated the correlation between the structure and release properties of solid lipid microparticles (MPs) with different liquid additives. The additives accelerated the conversion of the unstable alpha-form of tristearin to the stable beta-polymorph and caused structural modifications in the MPs. The presence of additives prolonged the drug release in water and resulted in higher release profiles in biorelevant media. The findings suggest that the release behavior can be influenced by the polymorphism and supramolecular-level structural modification of lipid formulations containing crystal modifiers.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Juulia Jarvinen, Ahmed B. Montaser, Santosh Kumar Adla, Jukka Leppanen, Marko Lehtonen, Kati-Sisko Vellonen, Tuomo Laitinen, Aaro Jalkanen, William F. Elmquist, Juri Timonen, Kristiina M. Huttunen, Jarkko Rautio
Summary: This study attempted to alter the brain distribution pattern of Palbociclib by creating and assessing two novel prodrugs. Although the prodrug design did not significantly improve Palbociclib brain delivery, the study provides valuable insights for future prodrug development and drug delivery strategies targeting specific transporters.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Review
Pharmacology & Pharmacy
Miao Wang, Xinyu Ma, Shiyu Zong, Yaqiong Su, Rui Su, Hong Zhang, Yang Liu, Chunliu Wang, Ye Li
Summary: This article discusses the potential and limitations of nasal administration in central nervous system drug delivery. Nasal gel viscosity can alleviate the impact of nasal mucociliary clearance on drug delivery, and materials such as gellan gum, chitosan, carbomer, cellulose, and poloxamer can be used to prepare nasal gels.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Bjarke Strom Larsen, Eric Kissi, Liebert Parreiras Nogueira, Natalja Genina, Ingunn Tho
Summary: This study investigates the influence of drug load and polymer molecular weight on the structure of 3D printed tablets. The results show that drug load and polymer molecular weight have a significant impact on the porosity and size of the tablets, while the effect of drug load on the total porosity of the tablets is minimal.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Zhentao Qiao, Fuhang Wang, Dongjian Han, Yuansong Zhuang, Qingjiao Jiang, Yi Zhang, Miaomiao Liu, Quanxu An, Zhiwei Wang, Deliang Shen
Summary: In this study, it was demonstrated that periadventitial delivery of rapamycin-fibrin glue (RPM-FG) can inhibit intimal hyperplasia (IH) in a rat carotid artery injury model without compromising re-endothelialization. This provides a promising direction for the future development of a safe, effective, and minimally invasive perivascular drug delivery method to treat vascular disease.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Neele Puhlmann, Rodrigo Vidaurre, Klaus Kuemmerer
Summary: Active pharmaceutical ingredients and their metabolites and transformation products are pollutants that can harm human and environmental health. Designing greener APIs is an effective strategy to address this issue. The drug discovery and development process can incorporate environmental parameters to achieve this design, and this process is highly flexible.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)