A5042621488- Drug Solubulity and Delivery Systems
- Crystallization and Solubility Studies
- Porphyrin Metabolism and Disorders
- Folate and B Vitamins Research
- Analytical Chemistry and Chromatography
- Protein purification and stability
- Analytical Methods in Pharmaceuticals
- Innovative Microfluidic and Catalytic Techniques Innovation
- RNA Interference and Gene Delivery
- Anesthesia and Sedative Agents
- Metabolism and Genetic Disorders
- Pharmaceutical studies and practices
- Animal Nutrition and Physiology
- Statistical Methods in Clinical Trials
- Metalloenzymes and iron-sulfur proteins
- Metal-Catalyzed Oxygenation Mechanisms
- Neurological diseases and metabolism
- Genetics and Neurodevelopmental Disorders
- Effects and risks of endocrine disrupting chemicals
- Cassava research and cyanide
- Heme Oxygenase-1 and Carbon Monoxide
- Coronary Interventions and Diagnostics
- Vascular anomalies and interventions
- Microplastics and Plastic Pollution
- Advanced Drug Delivery Systems
Merck & Co., Inc., Rahway, NJ, USA (United States)
2003-2024
United States Military Academy
2013-2022
University of Wisconsin–Madison
1998-2003
Massachusetts Institute of Technology
2003
The Graduate Center, CUNY
2000
The University of Texas Health Science Center at San Antonio
1999
Karlsruhe Institute of Technology
1994-1997
This manuscript represents the perspective of Dissolution Analytical Working Group IQ Consortium. The intent this is to highlight challenges of, and provide a recommendation on, development clinically relevant dissolution specifications (CRS) for immediate release (IR) solid oral dosage forms. A roadmap toward CRS IR products containing active ingredients with non-narrow therapeutic window discussed, within context mechanistic understanding, supported by in-human pharmacokinetic (PK) data....
A meeting that was organized by the Academy of Pharmaceutical Sciences Biopharmaceutics and Regulatory focus groups focused on challenges Developing Clinically Relevant Dissolution Specifications (CRDS) for Oral Drug Products. Industrial Scientists were involved in product development shared their experiences with vitro dissolution silico modeling approaches to establish clinically relevant specifications. The regulators perspectives acceptability these different strategies acceptable also...
The potential of lipid nanoparticles (LNPs) as nucleic acid delivery vehicles has been demonstrated in recent years, culminating the emergency use approval LNP-based mRNA SARS-CoV-2 vaccines late 2020. determination RNA content relative to LNP size can be important understanding efficacy and adverse effects. This work presents first description a facile rapid analytical method for online, size-dependent payload distribution measurement using data from multi-angle light scattering,...
The substrate‐dependent homolysis of the cobalt‐carbon bond and generation organic radicals in coenzyme‐B 12 –methylmalonyl‐CoA‐mutase complex have been demonstrated by EPR measurements. Both natural substrate methylmalonyl‐CoA, its 13 C‐substituted analogue non‐hydrolysable synthetic substrates succinyl‐dethia(carba)‐CoA, succinyl‐dethia(dicarba)‐CoA 4‐carboxy‐2‐oxo‐butyl‐CoA induced similar but not identical signals. 3‐Carboxypropyl‐CoA, a novel competitive inhibitor, has synthesised. Its...
Even in the enzyme-bound state dimethylbenzimidazole ligand dioldehydratase from Salmonella typhimurium remains bound to cobalt ion contrast some coenzyme B12 -dependent enzymes. Direct, ESR spectroscopic proof for this "base-on" binding mode was obtained by using a which one of nitrogen atoms 15 N labeled (see schematic representation on right).
The hydrate of glycolaldehyde is a substrate analogue that induces the formation cob(II)alamin and 5'-deoxyadenosine from adenosylcobalamin at active site dioldehydrase, resulting complex inactive. carbon atoms remain bound to this complex, it has been postulated first step or steps catalytic process on generate an intermediate undergoes destructive side reaction leading inactivation enzyme [Wagner, O. W., Lee, H. A., Jr., Frey, P. Abeles, R. (1966) J. Biol. Chem. 249, 1751−1762]. All...
A webinar series that was organised by the Academy of Pharmaceutical Sciences Biopharmaceutics focus group in 2021 focused on challenges developing clinically relevant dissolution specifications (CRDSs) for oral drug products. Industrial scientists, together with regulatory and academic came through a six webinars, to discuss progress field, emerging trends, areas continued collaboration harmonisation. Each also hosted Q&A session where participants could shared topic information. Although...
Fhit is the protein product of FHIT, a candidate human tumor suppressor gene. catalyzes hydrolysis diadenosine triphosphate (Ap3A) to AMP and ADP. here shown catalyze in H218O with production adenosine 5‘-[18O]phosphate ADP, proving that substitution water at Pα not Pβ. The chain fold similar galactose-1-phosphate uridylyltransferase, which functions by double-displacement mechanism through formation covalent nucleotidyl−enzyme intermediate overall retention configuration Pα. active site...
The adenosylcobalamin-dependent ribonucleoside triphosphate reductase (RTPR) from Lactobacillus leichmannii catalyzes the reduction of triphosphates to deoxyribonucleoside triphosphates. RTPR also exchange C5'-hydrogens adenosylcobalalamin with solvent hydrogen. A thiyl radical located on Cys 408 is generated by reaction adenosylcobalamin at active site and proposed be intermediate for both nucleotide 5'-hydrogen reactions. In present research, a stereochemical approach used study mechanism...
Novel analogues of methylmalonyl‐CoA and succinyl‐CoA have been prepared used for mechanistic investigations on the coenzyme‐B 12 ‐dependent mutase. 1‐Carboxyethyl‐CoA ( 1 ) 2‐carboxyethyl‐CoA 2 as well their sulphoxides 3 4 were moderately good inhibitors with K i values 4–20 times higher than m succinyl‐CoA. 2‐Carboxyethyl‐CoA its sulphoxide induced EPR signals when bound to enzyme–coenzyme‐B complex. The spectrum differed very much from those by other substrates. In case...
Apex vessels (previously known as PEAK vessels) are an important element of the dissolution scientist's toolbox and frequently used in pharmaceutical drug product development settings.However, their use has not translated widely into final approved quality control (QC) method.This Stimuli article aims to demonstrate significant benefit apex vessel relative standard overcoming coning for formulations that contain dense insoluble excipients.Industrial case studies outline benefits obtained by...