Quantifying the bitter masking effect of drug-cyclodextrin complexation: NMR-ROESY mixing time approach.

Taste, especially unpleasant taste, can be key for patient compliance. In the formulation development process, drug-cyclodextrin (CD) inclusion complexes are often used to improve the solubility of a drug and/or mask its bitterness. This study aimed to evaluate the bitter masking effect of CDs on different drugs using NMR-ROESY analysis, human sensory tests, and e-tongue measurements.

Purity Determination of Cyclophosphamide Hydrate by Quantitative P-NMR and Method Validation.

Recently, quantitative NMR (qNMR), especially H-qNMR, has been widely used to determine the absolute quantitative value of organic molecules. We previously reported an optimal and reproducible sample preparation method for H-qNMR. In the present study, we focused on a P-qNMR absolute determination method.

Stabilization by meglumine of an amine compound degraded by formaldehyde in tablets.

[3-[(2R)-[[(2R)-(3-Chlorophenyl)-2-hydroxyethyl]amino]proryl]-1H-indol-7-yloxy]acetic acid (AJ-9677), which was being developed as an antidiabetic, was observed to degrade in tablet preparations. The main degradation product in tablets, AD-9889, was a carbon adduct of the drug substance. When the drug substance was exposed to formaldehyde in aqueous solutions, a correlation was found between the level of formaldehyde and the quantity of AD-9889 formed during storage.

Generation of formaldehyde by pharmaceutical excipients and its absorption by meglumine.

Formaldehyde is a well-known air impurity. The possibility was investigated in this study that pharmaceutical excipients commonly used in oral solid dosage forms might also be sources of formaldehyde. The results showed that formaldehyde is generated by the excipients lactose, D-mannitol, microcrystalline cellulose, low-substituted hydroxypropylcellulose, magnesium stearate and light anhydrous silicic acid.

Isolation of a new antibiotic, alaremycin, structurally related to 5-aminolevulinic acid from Streptomyces sp. A012304.

A new antibiotic, which is structurally related to 5-aminolevulinic acid, a precursor of heme biosynthesis, and named alaremycin, was isolated from the culture broth of an actinomycete strain through a random screening with the blue assay to detect the formation of anucleate cells in Escherichia coli. The producing strain was identified as Streptomyces sp. by morphological, physiological, chemical and genetic criteria.

Syntheses and properties of the major hydroxy metabolites in humans of blonanserin AD-5423, a novel antipsychotic agent.

Two major metabolites in humans of blonanserin, 2-(4-ethyl-1-piperazinyl)-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta-[b]pyridine (code name AD-5423), were synthesized. The first, 7-hydroxylated AD-5423, was synthesized through a four-step process starting from 4-fluorobenzoylacetonitrile (1), and the second, 8-hydroxylated AD-5423, a nine-step process also from 1. The optical resolution, structures, and receptor binding properties of the metabolites were documented.

Synthesis and antibacterial activity of novel and potent DNA gyrase inhibitors with azole ring.

The 4-piperidyl moiety and the pyrazole ring in 1-(3-chlorophenyl)-5-(4-phenoxyphenyl)-3-(4-piperidyl)pyrazole 2, which has previously shown improved DNA gyrase inhibition and target-related antibacterial activity, were transformed to other groups and the in vitro antibacterial activity of the synthesized compounds was evaluated. The selected pyrazole, oxazole and imidazole derivatives showed moderate inhibition against DNA gyrase and topoisomerase IV with similar IC(50) values (IC(50)=9.4-25 microg/mL).