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.
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
Chemistry, Multidisciplinary
Tibor Dubaj, Katarina Kozics, Monika Sramkova, Alena Manova, Neus G. Bastus, Oscar H. Moriones, Yvonne Kohl, Maria Dusinska, Elise Runden-Pran, Victor Puntes, Andrew Nelson, Alena Gabelova, Peter Simon
Summary: Data for assembling a physiologically-based pharmacokinetic (PBPK) model for nanoparticles (NPs) are relatively scarce, leading to a trend of extrapolating results from in vitro and in silico studies to in vivo nanoparticle hazard and risk assessment. To evaluate the reliability of this approach, a pharmacokinetic study was conducted using the same polyethylene glycol-coated gold nanoparticles (PEG-AuNPs) in vitro and in vivo. The study found notable differences in the internalized amount of Au between individual cell lines and corresponding tissues in vivo, indicating the caution needed when extrapolating in vitro data to predict the in vivo NP burden and response to exposure.
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
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)
Review
Chemistry, Multidisciplinary
Tejas Girish Agnihotri, Amit Alexander, Mukta Agrawal, Sunil Kumar Dubey, Aakanchha Jain
Summary: Understanding the interaction between nanoparticles and biological systems is a challenge in nanotherapeutics. Protein corona plays a crucial role in cellular uptake and in vivo behavior of nanoparticles. In vitro dissolution testing and in vitro in vivo correlation (IVIVC) are useful approaches to evaluate the fate of nanoparticles. This review emphasizes the importance of protein corona, factors affecting the interaction, and various dissolution media for different nanocarrier systems, and discusses the limitations and regulatory perspective of IVIVC.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Pharmacology & Pharmacy
Janis Niessen, Alvaro Lopez Marmol, Ruba Ismail, Julia T. Schiele, Karola Rau, Andrea Wahl, Kerstin Sauer, Oliver Heinzerling, Jorg Breitkreutz, Mirko Koziolek
Summary: The aim of this study was to develop a staged biopharmaceutical test protocol to assess ASD-based pediatric formulations. The results showed that controlled disintegration and dissolution could prevent excessive primary precipitation. However, the performance of mini-tablet and tablet formulations did not improve in tiny-TIM testing. This study supports the development of ASD-based pediatric formulations and improves the understanding of drug release under variable physiological conditions.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2023)
Article
Pharmacology & Pharmacy
Patrick J. O'Dwyer, Karl J. Box, Georgios Imanidis, Maria Vertzoni, Christos Reppas
Summary: This study evaluated various in vitro methods for assessing the intraluminal performance of low solubility drugs in the fasted state, finding that the choice of methodology depends on the characteristics of the drug substance. Specifically, for salts of acidic drugs like diclofenac potassium, availability and ease of operation of the apparatus are key factors, while for weakly alkaline substances like ritonavir, dynamic dissolution process simulation and specific information requirements are crucial in method selection. Early in drug development, the use of small-scale systems may be necessary due to limited drug substance quantities available.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
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
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
Pharmacology & Pharmacy
Christi A. Wilkins, Lissinda H. du Plessis, Joe M. Viljoen
Summary: The study investigated the use of directly compressed lipid matrix tablets as drug delivery systems to enhance the dissolution and release kinetics of highly lipophilic antimalarial drugs, potentially improving current malaria treatment regimens.
Article
Medicine, Research & Experimental
Toshihide Takagi, Takato Masada, Keiko Minami, Makoto Kataoka, Ken-Ichi Izutsu, Kazuki Matsui, Shinji Yamashita
Summary: A methodology for simulating the change in gastrointestinal fluid pH and composition during the transition of orally administered drugs from the stomach to the small intestine was developed. The system was used for in vitro sensitivity analysis on the dissolution of weakly basic drugs, showing small intrasubject variance for some drugs in human bioequivalence studies, while others were affected by fluctuations in gastric pH.
MOLECULAR PHARMACEUTICS
(2021)
Article
Pharmacology & Pharmacy
Snezana Radivojev, Gerfried Luschin-Ebengreuth, Joana T. Pinto, Peter Laggner, Alessandro Cavecchi, Nicola Cesari, Massimo Cella, Fabrizio Melli, Amrit Paudel, Eleonore Froehlich
Summary: Orally inhaled products are receiving increasing attention for the treatment of various diseases via pulmonary delivery. This study used an in vitro-in silico approach to investigate the biopharmaceutics behavior of inhaled Salbutamol Sulphate and Budesonide. The results showed that media containing lipids and albumin had the most significant impact on Budesonide solubility, while no notable impact was seen for Salbutamol Sulphate. The use of simple media like phosphate buffer saline may be sufficient for soluble and permeable drugs, but may be limited for poorly soluble drugs due to potential interactions in vivo.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Article
Pharmacology & Pharmacy
Katharina Krollik, Andreas Lehmann, Christian Wagner, Jonathan Kaidas, Holger Kubas, Werner Weitschies
Summary: Biorelevant solubility and dissolution testing is an important tool in pharmaceutical development. However, the use of biorelevant media does not always match the solubility data observed in human intestinal fluids. This study found that the medium primarily affects dissolution kinetics, and the unique buffering properties of bicarbonate buffer play a special role in simulating conditions in human intestinal fluids. Further investigation is needed to understand the factors causing differences in solubility and dissolution behavior between phosphate- and bicarbonate-buffered biorelevant media.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2022)
Article
Pharmacology & Pharmacy
Dora Csicsak, Rita Szollath, Szabina Kadar, Rita Ambrus, Csilla Bartos, Emese Balogh, Istvan Antal, Istvan Koteles, Petra Tozser, Vivien Bardos, Peter Horvath, Eniko Borbas, Krisztina Takacs-Novak, Balint Sinko, Gergely Volgyi
Summary: Particle size reduction is commonly used to improve drug formulation solubility and dissolution. This study investigated the effect of particle size, pH, biorelevant media and polymers on the solubility and dissolution of drug formulations using three model compounds. Micronization resulted in a faster dissolution without affecting drug equilibrium solubility, while nanonization improved equilibrium solubility but required appropriate excipient selection. PVPK-25 had an increasing effect on solubility and better inhibition of particle aggregation compared to PVA.