RESUMO
Preparation of starch microspheres using epichlorohydrin is a time consuming method and requires around 18 hr for cross-linking reaction. To reduce reaction time, terbutaline sulfate (TBS) loaded degradable starch microspheres (DSM) were prepared using formaldehyde as the cross-linking agent. All microspheres were spherical in shape and had a porous, rough surface with a mean particle size of 18-24 microm. Whatever the cross-linking time, it was seen that the release of the TBS was not complete during the release experiments. The influence of enzyme on the degradation of microspheres was moderate. Following intravenous administration, initial uptake of microspheres by the lung was higher than those of other organs.
Assuntos
Química Farmacêutica/métodos , Reagentes de Ligações Cruzadas/química , Formaldeído/química , Amido/farmacocinética , Terbutalina/farmacocinética , Agonistas Adrenérgicos beta/administração & dosagem , Agonistas Adrenérgicos beta/química , Agonistas Adrenérgicos beta/farmacocinética , Animais , Área Sob a Curva , Disponibilidade Biológica , Difusão , Relação Dose-Resposta a Droga , Composição de Medicamentos/métodos , Liofilização/métodos , Meia-Vida , Injeções Intravenosas , Pulmão/metabolismo , Masculino , Camundongos , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Amido/administração & dosagem , Amido/química , Terbutalina/administração & dosagem , Terbutalina/química , Distribuição TecidualRESUMO
Terbutaline sulfate is widely used as a bronchodilator for the treatment of bronchial asthma, chronic bronchitis and emphysema. As it has a short biological half-life, a long acting terbutaline sulfate formulation is desirable to improve patient compliance. Bovine serum albumin microspheres were prepared by an emulsion polymerization method using glutaraldehyde as the crosslinking agent. All microspheres were spherical and smooth with the mean particle size in the range of 22-30 microm. Drug release from the BSA microspheres displayed a biphasic pattern characterized by an initial fast release, followed by a slower release. The released amount was decreased with an increase in the glutaraldehyde concentration. In the absence of trypsin, the time required for complete degradation of microspheres was increased from 144 to 264 h when the glutaraldehyde concentration increased from 0.1 to 0.7 ml. In the presence of trypsin, a linear relationship was obtained between the degradation rates and trypsin concentrations, indicating that saturation was not reached under the experimental conditions. Biodistribution studies indicated that the degree of uptake by the lungs was higher than that of the other organs. All these results demonstrated that terbutaline sulfate loaded microspheres can be used for passive lung targeting.
