Search results for "Active ingredient"
showing 10 items of 56 documents
Pressure-Stabilized Solvates of Xylazine Hydrochloride
2016
High pressure strongly favors the highest-density polymorph Z of active pharmaceutical ingredient 2-(2,6-xylidino)-5,6-dihydro-4H-1,3-thiazine hydrochloride (xylazine hydrochloride, XylHCl) up to about 0.1 GPa only, but still higher pressure destabilizes this structure. Above 0.1 GPa, XylHCl preferentially crystallizes as solvates with CH2Cl2, CHCl3, or (CH3)2CHOH depending on the solvent used. However, when XylHCl·H2O is dissolved in any of these solvents, the high-pressure crystallizations yield the hydrate XylHCl·H2O only. The single crystals of the CH2Cl2, CHCl3, and (CH3)2CHOH solvates could be grown in situ in a diamond anvil cell, which allowed their structure determination from the …
ChemInform Abstract: High-Resolution Solid-State NMR Spectroscopy of Steroids and Their Derivatives
2013
Abstract: Steroids are an important class of organic compounds containing a vast array of biologically and physiologically essential molecules. Due to their availability, relatively straightforward derivatizability, and endogeneity, they are widely used in pharmacological applications. The investigation of molecular and physicochemical properties of active pharmaceutical ingredients (APIs) in the solid state is important, because these properties are directly related to their pharmacological activity. Several methods are available for this purpose. Solid-state NMR spectroscopy offers a nondestructive and flexible technique, providing both structural and dynamic information. It can be applie…
High-Resolution Solid-State NMR Spectroscopy of Steroids and Their Derivatives
2013
Abstract: Steroids are an important class of organic compounds containing a vast array of biologically and physiologically essential molecules. Due to their availability, relatively straightforward derivatizability, and endogeneity, they are widely used in pharmacological applications. The investigation of molecular and physicochemical properties of active pharmaceutical ingredients (APIs) in the solid state is important, because these properties are directly related to their pharmacological activity. Several methods are available for this purpose. Solid-state NMR spectroscopy offers a nondestructive and flexible technique, providing both structural and dynamic information. It can be applie…
The sustainable synthesis of levetiracetam by an enzymatic dynamic kinetic resolution and an ex-cell anodic oxidation
2021
Levetiracetam is an active pharmaceutical ingredient widely used to treat epilepsy. We describe a new synthesis of levetiracetam by a dynamic kinetic resolution and a ruthenium-catalysed ex-cell anodic oxidation. For the enzymatic resolution, we tailored a high throughput screening method to identify Comamonas testosteroni nitrile hydratase variants with high (S)-selectivity and activity. Racemic nitrile was applied in a fed-batch reaction and was hydrated to (S)-(pyrrolidine-1-yl)butaneamide. For the subsequent oxidation to levetiracetam, we developed a ligand-free ruthenium-catalysed method at a low catalyst loading. The oxidant was electrochemically generated in 86% yield. This route pro…
Efficacy of an amine fluoride-triclosan mouthrinse as compared to the individual active ingredients
2003
Background: The purpose of the clinical study was to examine the antibacterial and plaque-reducing properties of mouthrinses containing triclosan (TRI), amine fluoride (AmF), and the combination of both (AFT) on 4-day plaque regrowth. A placebo solution (PLA) and a 0.2% chlorhexidine solution (CHX) served as negative and positive controls, respectively. Materials & Methods: After a professional tooth cleaning (day 0), 15 volunteers refrained from all mechanical oral hygiene measures for the next 96 h and rinsed instead twice daily for 1 min with 10 ml of one of the five randomly assigned solutions. Plaque index (PlI), which was assessed after 24 and 96 h (PlI1, PlI2), and plaque area of the…
The impact of the EMA change in definition of "dose" on the BCS dose-solubility ratio: a review of the biowaiver monographs.
2013
The Biopharmaceutics Classification System (BCS) defines the solubility characteristics of an active pharmaceutical substance based on its dose-solubility ratio: for highly soluble drugs this ratio is less than 250 mL over a defined pH range. Prior to the revision of the European Medicines Agency (EMA, formerly EMEA) guideline in 2010, the "dose" in this ratio was consistently defined by the US FDA, the EMA, and the WHO biowaiver guidelines as the highest dosage strength. However, in the revised EMA guideline, the dose is defined as the highest single dose administered according to the Summary of Product Characteristics. The new EMA criterion for highly soluble may be closer to the actual c…
2006
Six-Step Gram Scale Synthesis of the HIV Integrase Inhibitor Dolutegravir Sodium
2021
A short and practical synthesis for preparing the active pharmaceutical ingredient dolutegravir sodium was investigated. The convergent strategy developed herein starts from 3-(R)-amino-1- butanol and builds up the BC ring system in 76% isolated yield over four steps. Ring A was constructed by a one-pot 1,4-addition to diethyl-(2E/Z)-2-(ethoxymethylidene)-3-oxobutandioate and subsequent MgBr2·OEt2-mediated regioselective cyclization. Amide formation with 2,4- difluorobenzylamine was either performed from the carboxylic acid or through aminolysis of the corresponding ester precursor. Final salt formation afforded dolutegravir sodium in 48–51% isolated yield (HPLC-purity: 99.7–99.9%) over six…
Effects of controlled-release on the pharmacokinetics and absorption characteristics of a compound undergoing intestinal efflux in humans
2006
Abstract Objective The number of active pharmaceutical ingredients (API) undergoing inhibitable and saturable intestinal efflux is considerable. As a consequence, absorption and bioavailability may depend on the intestinal concentration profile of the drug and may vary as a function of dose and release rate of the drug from the dosage form. The impact of controlled versus immediate-release on the absorption of P-glycoprotein substrates is currently unknown. Thus, the main focus of the present study was a comparison of the pharmacokinetics of the P-gp model substrate talinolol following administration of immediate-release (IR) and controlled-release (CR) tablets to healthy human volunteers w…
IVIVC for fenofibrate immediate release tablets using solubility and permeability as in vitro predictors for pharmacokinetics.
2010
The goal of this study was to investigate the in vitro-in vivo correlation (IVIVC) for fenofibrate immediate release (IR) tablet formulations based on MeltDose-technique. The in vitro determined drug solubility and permeability data were related to the C(max) values observed from two in vivo human studies. Solubility and permeation studies of fenofibrate were conducted in medium simulating the fasted state conditions in the upper jejunum, containing the surfactant compositions of the six formulations at different concentrations. The behavior of all surfactant compositions was characterized by surface tension, dynamic light scattering, and cryo-TEM. The obtained solubility and permeation dat…