Experimental and Computational Studies of Physicochemical Properties Influence NSAID-Cyclodextrin Complexation

The objective of this research was to investigate physicochemical properties of an active pharmaceutical ingredient (API) that influence cyclodextrin complexation through experimental and computational studies. Native β-cyclodextrin (B-CD) and two hydroxypropyl derivatives were first evaluated by conventional phase solubility experiments for their ability to complex four poorly water-soluble nonsteroidal anti-inflammatory drugs (NSAIDs). Differential scanning calorimetry was used to confirm complexation. Secondly, molecular modeling was used to estimate Log P and aqueous solubility (S _o) of the NSAIDs. Molecular dynamics simulations (MDS) were used to investigate the thermodynamics and geometry of drug-CD cavity docking. NSAID solubility increased linearly with increasing CD concentration for the two CD derivatives (displaying an A_L profile), whereas increases in drug solubility were low and plateaued in the B-CD solutions (type B profile). The calculated Log P and S _o of the NSAIDs were in good concordance with experimental values reported in the literature. Side chain substitutions on the B-CD moiety did not significantly influence complexation. Explicitly, complexation and the associated solubility increase were mainly dependent on the chemical structure of the NSAID. MDS indicated that each NSAID-CD complex had a distinct geometry. Moreover, complexing energy had a large, stabilizing, and fairly constant hydrophobic component for a given CD across the NSAIDs, while electrostatic and solvation interaction complex energies were quite variable but smaller in magnitude.     

Amino acid composition of band 3 protein from red blood cells of normal and epileptic children

Amino acid analyses of the band 3 protein purified from erythrocyte membranes of control and epileptic children showed that no major structural abnormalities of this protein could be linked with the red blood cell membrane alterations previously described in child epilepsy and, consequently, the molecular basis of these alterations should be looked for elsewhere.     

A nonclassical radiation process (Comorosan effect) studied by a photographic technique

Unconventional and highly unexpected results in the Comorosan Effect have been obtained in a photographic study using N-methyl-4-aminophenol (metol) as the developer. Before dissolving the developer was irradiated with green light (lambda = 546 nm) for various distinct periods of time (5, 10 and 15 seconds). A significant difference was observed in the rates of the developing process for different samples of the developer which had been irradiated for 5 seconds compared to non-irradiated controls, but no differences were observed for samples irradiated for 10 or 15 seconds, respectively. This unusual radiation phenomenon is similar to the Comorosan Effect by which rates of enzymatic reactions are manifested and significantly influenced by prior irradiation of the enzyme substrates, but only for times which are certain multiples of 5 seconds.