BackgroundA clinical trial sponsored by our hospital wished to compare HMG-CoA reductase inhibitors versus placebo for children with genetic diseases. For this purpose, and because the dosage in unavailable, our laboratory is in charge of the galenic development of simvastatin capsules and its placebo. According to GMP, the stability of the simvastatin capsule is evaluated.PurposeDevelopment and validation of a stability indicating HPLC-UV method for simvastatin capsules.Material and methodsThe HPLC system is a Thermofisher P4000. The column is an inertsil-CN, 250×4.6 mm with 5 µm particle. The mobile phase is an isocratic elution made up of 0.1% acetic acid buffer/methanol (50:50 v/v) at 1 mL/min flow rate. λ is included between 200 and 400 nm. Maximal absorbance of simvastatin is 237 nm. Calibration standard curve is between 30 and 70 µg/mL. Niacin is used as the internal standard. Linearity, trueness, accuracy and limits of quantification were evaluated according to SFSTP recommendations. Impurities were searched from SCR impurities of simvastatin dust according to pharmacopoeia 8.0. The matrix effect was evaluated.ResultsLinearity for simvastatin was validated with r² >0.99 and SD <15%. Recoveries and bias were < 15% for each validation standard. High and low limits of detections were far from the calibration standard curves. There was no matrix effect with the excipients. All impurities were detected and separated with a resolution >1.5.ConclusionA simple and rapid stability indicating HPLC-UV method was developed and validated according to ICH and SFSTP international recommendations. It will be used to evaluate the stability of our simvastatin capsule. We already have 3 months of validated stability.No conflict of interest

No abstract

BackgroundMannitol is considered the gold standard hyperosmolar agent to decrease intracranial pressure (ICP) after traumatic brain injury. However, solutions of mannitol may crystallise when exposed to low temperatures, for example at high altitude or during helicopter rescues. If crystals are observed, the container should be warmed, shaken and then cooled to body temperature before administration which is inappropriate in daily emergency practice. Several studies show that hypertonic saline solution (HTSS) is comparable or potentially superior to mannitol: furthermore HTSS might have less adverse effect than mannitol and does not crystallise with low temperature. HTSS only exists in 500 mL glass vials, unfit for emergency practices which need compact unbreakable packaging.PurposeTo provide for emergency practices a ready-to-use HTSS of 7.5% sodium chloride infusion bag.Material and methodsInfusion bags were produced by aseptic process using the BAXA® EM2400 compounder. Ingredients used were sterile sodium chloride 20% (AGEPS®) and water for injectable preparation (Bbraun®) filled in an ethyl vinyl acetate infusion bag of 100 ml. Bags were stored at room temperature without light protection. Microbiological stability was assessed by performing sterility and endotoxin tests. The physicochemical study was performed by determining visual aspect, osmolality, sodium and chloride concentration at 0, 30 and 90 days.ResultsNeither precipitate nor any change in colour was observed after 90 days. Ion concentrations remained unchanged with 1320 mM (+3%); 1290 mM (+1%); 1240 mM (−3%) and osmolality of the HTSS were found to be 2560 mosm/L (0%); 2420 (-6%); and 2350 mosm/L (9%) respectively at 0, 30 and 90 days. At each time point, all microbiological results were negative.ConclusionThe automated compounding ensures quality and safety of production for a ready-to-use HTSS of 7.5% sodium chloride with a best-before-date of 90 days. The stability study is still on-going.Reference and/or Acknowledgements1. Helmy A, Vizcaychipi M, Gupta AK: Traumatic brain injury: intensive care management. Br J Anaesth, 2007; 99: 32–42.No conflict of interest

No abstract