[Injectable hospital preparation of valine labeled with the carbon 13 and nitrogen 15 (5 mg/mL) for a clinical trial on the brain tumor metabolism: Pharmaceutical control of active pharmaceutical ingredient and stability study of the finished product]. / Préparation hospitalière injectable de valine marquée au carbone 13 et à l'azote 15 (5mg/mL) pour un essai clinique sur le métabolisme tumoral cérébral : contrôle pharmaceutique de la substance active et étude de stabilité du produit fini.

INTRODUCTION: The L-Valine labeled (L-[U-(13)C,(15)N] Val) is a stable isotopic tracer administered by parenteral route within the framework of a new clinical research program concerning the brain tumor metabolism. To meet regulatory requirements and have ready to use solution with an expiration date, a pharmaceutical control of active pharmaceutical ingredient followed by stability study of hospital preparation were realised. MATERIALS AND METHODS: After the pharmaceutical control of the L-[U-(13)C,(15)N] Val, the hospital preparation was prepared according to the good manufacturing preparation. Prepared bottles were stored at 5°C±3°C and 25°C±2°C for six months. The stability of the preparation was determined by physico-chemical controls (pH, osmolality, sub-visible particles, L-[U-(13)C,(15)N] Val concentration, sodium concentration, isotopic enrichment) and microbiological (bacterial endotoxin and sterility). RESULTS: Concentrations of L-[U-(13)C, (15)N] Val and sodium does not significantly decrease during the stability study. In parallel, no change in pH and osmolality were highlighted. Isotopic enrichment higher than 99.9% reflected the stability of labeling of L-valine molecule. The sub-visible particles, the bacterial endotoxin and sterility were in accordance with the European Pharmacopoeia attesting limpidity, apyrogenicity and sterility of this injectable preparation. DISCUSSION AND CONCLUSION: The stability of this hospital preparation of L-[U-(13)C, (15)N] Val has been demonstrated for six months at 5°C±3°C and 25°C±2°C, ensuring a parenteral administration as part of the clinical trial.

NMR and ESR study of amphotericin B interactions with various binary phosphatidylcholine/phosphatidylglycerol membranes.

Several biologically relevant phospholipids are considered as potential excipients for IV administration liposome's formulation of AMB (Biopharmaceututics Classification System Class IV). On the basis of in vivo bioavaibility studies, DMPC and DMPG were ranked as the first potent encapsulation enhancers for this model drug, especially if one expects to target DMPG rich systems as pulmonary surfactant. Subsequently, dispersions (multilayers) of DMPC, DMPG or in binary systems with various molar ratios were prepared with or without AMB (molar ratios AMB/lipid) and further investigated using the 1H-,31P-NMR methods. It was found that equimolar preparations of DMPG/DMPG exhibited both a good encapsulation of AMB, while also probably able to target pulmonary surfactant. Besides DMPG did not exhibit the same solubilization properties. Conversely, no targeting by DMPC dispersion alone was expected, even if a good solubilization was obtained.