Crystal Structures and Physicochemical Properties of Diltiazem Base, Acetylsalicylate, Nicotinate and L-Malate

Diltiazem is a drug used as a calcium channel blocker in the treatment of cardiovascular disorders. Because of poor aqueous solubility of the drug, hydrochloride salt has been marketed. Due to the short elimination half-life of diltiazem, extended-release formulations were developed. In the present work, the crystal engineering approach has been employed to obtain diltiazem forms with lower water solubility by treating with carboxylic acids. Three molecular salts of diltiazem with aspirin, niacin and L-malic acid were synthesized and characterized by a single crystal and powder XRD, DTA, solid state CP-MAS, NMR and UV/vis techniques. The single crystal structure determination allowed us to study supramolecular structures and proton transfer interactions from carboxylic acids to diltiazem in the solid state, while NMR studies – interaction in solution. In crystal, the N,N-(dimethyl)ethylamine fragment of the drug molecule interacts with carboxylic groups of the acids to form heterosynthons. The maximum 40-fold decrease of aqueous solubility is achieved for diltiazem acetylsalicylate hydrate in comparison with the solubility of diltiazem hydrochloride

Iron Oxide Superparamagnetic Nanocarriers Bearing Amphiphilic N-Heterocyclic Choline Analogues as Potential Antimicrobial Agents

Magnetic nanoparticles represent an advanced tool in biomedicine because they can be simultaneously functionalized and guided using a magnetic field. Iron oxide magnetic nanoparticles precoated with oleic acid and bearing novel antimicrobial N-heterocyclic choline analogues, namely O-, N- and O,N-bis-undecyl-substituted N-(2-hydroxyethyl)-1,2,3,4-tetrahydroisoquinolinium derivatives, have been obtained as potential biomedical agents for drug delivery and antimicrobial therapy. Structural and size determinations for the novel synthesized magnetic nanosystems were carried out based upon magnetogranulometry, dynamic light-scattering measurements and X-ray diffraction analysis. The most expected iron oxide core diameter was 6.2-10.5 nm. The magnetization analyses showed that the particles are superparamagnetic at room temperature. Aqueous magnetic fluids of the synthesized nanoparticles were examined in vitro concerning Gram-positive (Staphylococcus aureus MSCL 334, Bacillus cereus MSCL 330) and Gram-negative (Escherichia coli MSCL 332, Pseudomonas aeruginosa MSCL 331, Proteus mirabilis MSCL 590) bacterial strains and fungi (Candida albicans MSCL 378, Aspergillus niger MSCL 324). It was found that the samples have magnetic properties and possess antimicrobial activity. The minimum inhibitory concentration against S. aureus for the most active magnetic fluid was determined as 16 μg ml^-1