ABSTRACT
Solid dispersions have been used as a strategy to improve the solubility, dissolution rate, and bioavailability of poor water-soluble drugs. The increase of the dissolution rate presented by (5Z)-3-(4-chloro-benzyl)-5-(4-nitro-benzylidene)-imidazolidine-2,4-dione (LPSF/FZ4) from the solid dispersions is related to the existence of intermolecular interactions of hydrogen bond type (>N-H···O<) between the amide group (>N-H) of the LPSF/FZ4 and the ether group (-O-) of the polyethyleneglycol polymer, or the carbonyl (C=O) of the polyvinylpyrrolidone polymer (PVP). The intensity of these interactions is directly reflected in the morphology acquired by LPSF/FZ4 in these systems, where a new solid phase, in the form of amorphous aggregates of irregular size, was identified through scanning electron microscopy and confirmed in the characterizations achieved using X-ray diffraction and thermal analysis of DSC. The solid dispersions with the polymer PVP, in higher concentrations, were revealed to be the best option to be used in the formulations of LPSF/FZ4 in both theoretical and experimental studies.
Subject(s)
Drug Delivery Systems , Hydantoins/chemistry , Schistosomicides/chemistry , Dosage Forms , Drug Carriers , Drug Compounding , Hydantoins/pharmacology , Models, Molecular , Polyethylene Glycols/chemistry , Polymers/chemistry , Povidone/chemistry , Schistosomicides/pharmacology , SolubilityABSTRACT
The N-alkylated derivatives from nitrofurazone were synthesised and evaluated in vitro for their efficacy as antimicrobial agents against representative strains, including methicillin-resistant Staphylococcus aureus (MRSA). The derivative 2a demonstrated greater activity than the prototype and was comparable to currently used antimicrobial drugs.
Subject(s)
Anti-Bacterial Agents , Antifungal Agents , Drug Design , Nitrofurazone , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Microbial Sensitivity Tests , Molecular Structure , Nitrofurazone/chemical synthesis , Nitrofurazone/chemistry , Nitrofurazone/pharmacology , Structure-Activity RelationshipABSTRACT
The geometries of three isomers of the C2H4O...2HF tri-molecular heterocyclic hydrogen-bonded complex were examined through B3LYP/aug-cc-pVDZ calculations. Analysis of structural parameters, determination of CHELPG (charge electrostatic potential grid) intermolecular charge transfer, interpretation of infrared stretching modes, and Bader's atoms in molecules (AIM) theory calculations was carried out in order to characterize the hydrogen bonds in each isomer of the C2H4O...2HF complex. The most stable structure was determined through the identification of hydrogen bonds between C2H4O and HF, (O...H), as well as in the hydrofluoric acid dimer, (HF(D-R)...HF(D)). However, the existence of a tertiary interaction (F(lambda)...H(alpha)) between the fluoride of the second hydrofluoric acid and the axial hydrogen atoms of C2H4O was decisive in the identification of the preferred configuration of the C2H4O...2HF system.
