Stability of -Acetylcysteine (NAC) in Standardized Pediatric Parenteral Nutrition and Evaluation of ,-Diacetylcystine (DAC) Formation.

The ESPGHAN/ESPEN/ESPR-Guidelines on pediatric parenteral nutrition (PPN) recommend the administration of the semiessential amino acid (AA) cysteine to preterm neonates due to their biochemical immaturity resulting in an inability to sufficiently synthetize endogenous cysteine. The soluble precursor -acetylcysteine (NAC) is easily converted into bioavailable cysteine. Its dimer ,-diacetylcystine (DAC) is almost unconvertable to cysteine when given intravenously resulting in a diminished bioavailability of cysteine.

The apparent solubilizing capacity of simulated intestinal fluids for poorly water-soluble drugs.

Drug solubility testing in biorelevant media has become an indispensable tool in pharmaceutical development. Despite this importance, there is still an incomplete understanding of how poorly soluble compounds interact with these media. The aim of this study was to apply the concept of the apparent solubilization capacity to fasted and fed state simulated intestinal fluid (FaSSIF and FeSSIF, respectively).

Instant solubilization of poorly water-soluble drugs by in-situ loading of aqueous phospholipid dispersions suitable for parenteral administration.

The features of a new, in situ method for solubilizing poorly soluble drugs (SupraVail Instant Solubilization) are demonstrated. The resulting formulations are suitable for parenteral administration in preclinical and clinical studies. The technique avoids drug precipitation upon dilution and circumvents the need for co-administration of high organic solvent concentrations.

Easy access to phosphonothioates.

A new and particularly mild method for the formation of phosphorus-sulfur bonds has been achieved through base-catalyzed addition of thiocyanate to the corresponding H-phosphine oxide, phosphinate, or phosphonate. This reaction procedure offers many advantages: the use as starting material of a stable and not oxygen-sensitive phosphorus(v) species, particularly mild and nonaqueous reaction conditions and workup (a pivotal point for these sensitive phosphonothioates), and, through optimized access to thiocyanates, a wider scope of substrates. This method has been applied to achieve the synthesis of substrate analogues for the study of antibody-catalyzed hydrolysis of acetylcholinesterase inhibitor PhX (11).