The aim of this work was to develop a phosphate buffer based dissolution method for enteric-coated formulations with improved biopredictivity for fasted conditions.
In silico modeling of gastrointestinal drug absorption: predictive performance of three physiologically based absorption models
Gastrointestinal (GI) drug absorption is a complex process determined by formulation, physicochemical and biopharmaceutical factors, and GI physiology.
The solubility-permeability interplay and oral drug formulation design: Two heads are better than one
Poor aqueous solubility is a major challenge in today's biopharmaceutics. While solubility-enabling formulations can significantly increase the apparent solubility of the drug, the concomitant effect...
BDDCS, the Rule of 5 and drugability
The Rule of 5 methodology appears to be as useful today in defining drugability as when it was proposed, but recognizing that the database that we used includes only drugs that successfully reached the market.
Computational prediction of formulation strategies for beyond-rule-of-5 compounds
The physicochemical properties of some contemporary drug candidates are moving towards higher molecular weight, and coincidentally also higher lipophilicity in the quest for biological selectivity and specificity.
Characterizing the Dissolution Profiles of Supersaturable Salts, Cocrystals, and Solvates to Enhance In Vivo Oral Absorption
The purposes of this study were to elucidate the type-specific characteristics of salt, cocrystal, and solvate formulations upon dissolution and precipitation, and to clarify their effect on enhancing oral absorption.
LC-ESI-MS/MS estimation of loratadine-loaded self-nanoemulsifying drug delivery systems in rat plasma: Pharmacokinetic evaluation and computer simulations by GastroPlus™
A rapid, sensitive, and accurate bioanalytical method was established for the quantitation and pharmacokinetic investigation of loratadine (LTD) in rat plasma by liquid chromatography–electrospray ionization...
Methodology of oral formulation selection in the pharmaceutical industry
Pharmaceutical formulations have to fulfil various requirements with respect to their intended use, either in the development phase or as a commercial product.
Quantitative aspects of drug permeation across in vitro and in vivo barriers
The kinetics of permeation across epithelial and endothelial cell sheets and across cell membranes is determinant for the pharmacokinetics of a drug.
Synthesis and Preclinical Evaluation of Sulfonamido based [11C-Carbonyl]-Carbamates and Ureas for Imaging Monoacylglycerol Lipase
Monoacylglycerol lipase (MAGL) is a 33 kDa member of the serine hydrolase superfamily that preferentially degrades 2-arachidonoylglycerol (2-AG) to arachidonic acid in the endocannabinoid system.
Impact of curcumin on the pharmacokinetics of rosuvastatin in rats and dogs based on the conjugated metabolites
Plasma concentrations of curcumin-O-glucuronide (COG) and curcumin-O-sulfate (COS) significantly increased after Sprague-Dawley rats dealt with the Oatp inhibitor rifampicin, with the Cmax ascending 2.9...
Structure-based virtual screening, molecular docking, ADMET and molecular simulations to develop benzoxaborole analogs as potential inhibitor against Leishmania donovani trypanothione reductase
Visceral leishmaniasis (VL) is the most fatal form of leishmaniasis and it affects 70 countries worldwide. Increasing drug resistant for antileishmanial drugs such as miltefosine, sodium stibogluconate and...
Integration of Life-Stage Physiologically-Based Pharmacokinetic (PBPK) Models with Adverse Outcome Pathways (AOPs) and Environmental Exposure Models to Screen for Environmental Hazards
A computational framework was developed to assist in screening and prioritizing chemicals based on their dosimetry, toxicity, and potential exposures.
Comparative human in-vivo study of an immediate release tablet over-encapsulated by gelatin and hydroxypropyl methyl cellulose capsules – impact of dissolution rate on bioequivalence
Rapid and consistent in-vivo drug dissolution is critical for drug absorption. In-vitro dissolutions tests are used to predict in-vivo disintegration and dissolution properties of drug products.
Estimating Margin of Exposure to Thyroid Peroxidase Inhibitors Using High-throughput In Vitro Data, High-throughput Exposure Modeling, and Physiologically-Based Pharmacokinetic / Pharmacodynamic Modeling
Some pharmaceuticals and environmental chemicals bind the thyroid peroxidase (TPO) enzyme and disrupt thyroid hormone production.
In vitro and in vivo evaluations of the P-glycoprotein-mediated efflux of dibenzoylhydrazines
P-glycoprotein (P-gp) is a member of the ATP-binding cassette transporter family. It actively transports a wide variety of compounds out of cells to protect humans from xenobiotics.
Predicting biopharmaceutical performance of oral drug candidates–Extending the Volume to Dissolve Applied Dose concept
The purpose of the study was to experimentally deduce pH-dependent critical volumes to dissolve applied dose (VDAD) that determine whether a drug candidate can be developed...
Application of in vitro transmucosal permeability, dose number, and maximum absorbable dose for biopharmaceutics assessment during early drug development for intraoral delivery
Intraoral (IO) administration is a unique route that takes advantage of transmucosal absorption in the oral cavity to deliver a drug substance locally or systemically.
Evaluating the Impact of Uncertainties in Clearance and Exposure When Prioritizing Chemicals Screened in High-Throughput Assays
The toxicity-testing paradigm has evolved to include high-throughput (HT) methods for addressing the increasing need to screen hundreds to thousands of chemicals rapidly.
Use of Modeling and Simulation Tools for Understanding the Impact of Formulation on the Absorption of a Low Solubility Compound: Ciprofloxacin
This study explored the utility of mechanistic absorption models to describe the in vivoperformance of a low solubility/low permeability compound in normal healthy subjects.