RESUMO
The scale-up of the film coating process for the production of Bronchoretard pellets (theophylline, CAS 58-55-9) is an example for the successful setup of a modern production technology designed to meet the increasing GMP requirements while taking into consideration ecological and economical aspects. This technology provides a reduction in polymer losses on drying from approx. 20% to under 5% and a distinct improvement in the reproducibility of the in vitro dissolution profiles. Double batch sizes and higher spray rates allow for a substantially higher batch turnover. A production line installed exclusively for Bronchoretard pellets and specific process optimization measures resulted in considerably lower lag-times of the equipment.
Assuntos
Antiasmáticos/administração & dosagem , Teofilina/administração & dosagem , Antiasmáticos/economia , Preparações de Ação Retardada , Composição de Medicamentos , Reprodutibilidade dos Testes , Tecnologia Farmacêutica , Teofilina/economiaRESUMO
In a previous study a high first-pass metabolism of N-nitrosodi-[1-14C]amylamine (NDAA, 0.59-350 microM) has been shown in isolated perfused rat small intestinal segments. In the present work the identification of metabolites in samples of perfusate and absorbed fluid (absorbate) is reported. After HPLC enrichment and purification five metabolites could be identified by GLC-MS which are the result of omega- and omega-1-hydroxylation, N-nitrosoamyl-(5-hydroxyamyl)amine (NA5HAA), N-nitrosoamyl-(4-hydroxyamyl)amine (NA4HAA), N-nitrosoamyl-(4-oxoamyl)amine (NA4OAA), N-nitrosoamyl-(4-carboxybutyl)amine (NA4CBA), and N-nitroso-amyl-(2-carboxyethyl)amine (NA2CEA). In rat urine the presence of only two of these metabolites, NA4HAA and NA2CEA, has been reported in the literature.