RESUMEN
INTRODUCTION: As part of a hospital clinical research program on endoscopic curative treatment for early epithelial neoplastic lesions of the gastrointestinal tract, a new hospital sterile and non-pyrogenic preparation of fructose (5%)-glycerol (10%) was realized. Under pharmaceutical legislation, the provision of this hospital preparation involves of aseptic process validation and achieve a stability study. MATERIALS AND METHODS: After the aseptic process validation with Mediafill Test, the preparation was made under aseptic conditions associated with a sterilizing filtration according to the good practices preparation. Prepared flexible bags (100mL of solution) were stored for one year in a climatic chamber (25±2°C). To assess stability, the physicochemical controls (fructose concentration, glycerol concentration, hydroxy-methyl-5 furfural [5-HMF] concentration, sodium concentration, pH measure, osmolality and sub-visible particles count) and microbiological (bioburden, bacterial endotoxin and sterility) were performed at regular intervals for one year. RESULTS: Neither significant decrease of fructose concentration, glycerol concentration and sodium concentration nor pH, 5-HMF, osmolality variations out of specifications were observed for one year. The sub-visible particles count, 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 hospital preparation was stable over one year at 25±2°C, ensuring safe administration in humans within the framework of this clinical research.
Asunto(s)
Fructosa/administración & dosificación , Glicerol/administración & dosificación , Carcinoma/tratamiento farmacológico , Estabilidad de Medicamentos , Almacenaje de Medicamentos , Endoscopía , Fructosa/química , Neoplasias Gastrointestinales/tratamiento farmacológico , Glicerol/química , Reproducibilidad de los Resultados , EsterilizaciónRESUMEN
INTRODUCTION: The L-leucine labeled (L-[U-(13)C] Leu) is a stable isotopic tracer administered by parenteral route within the framework of a new clinical research program concerning the diagnosis of the Alzheimer's disease. To meet regulatory requirements and have ready to use solution with an expiration date, a pharmaceutical control of raw materials and the finished product followed by a stability study were realised. MATERIALS AND METHOD: After the pharmaceutical control of raw materials, the solution of L-[U-(13)C] Leu was prepared according to the good practices preparation. Prepared bottles were stored for 1 year of a share in a climatic chamber (25 °C±2 °C) and the other in a refrigerator (5 °C±3 °C). To assess stability, the physicochemical controls (pH, osmolality, sub-visible particles, L-[U-(13)C] Leu concentration, sodium concentration, isotopic enrichment) and microbiological (bacterial endotoxin and sterility) were performed at regular intervals for 1 year. RESULTS: Neither significant decrease of L-[U-(13)C] Leu concentration and sodium concentration nor pH and osmolality variation were observed for 1 year. Isotopic enrichment higher than 99.9% reflected the stability of labelling of L-leucine 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 injectable preparation of L-[U-(13)C] Leu was stable after 1 year for two preservation conditions, ensuring to safety for administration for human within the framework of this clinical research.
Asunto(s)
Enfermedad de Alzheimer/diagnóstico por imagen , Marcaje Isotópico/métodos , Leucina/química , Radiofármacos/química , Isótopos de Carbono , Estabilidad de Medicamentos , Almacenaje de Medicamentos , Humanos , Soluciones FarmacéuticasRESUMEN
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.