A novel pH-dependent gradient-release delivery system for nitrendipine: I. Manufacturing, evaluation in vitro and bioavailability in healthy dogs

摘要: Abstract A novel pH-dependent gradient-release delivery system was developed by mixing three kinds of microspheres. Nitrendipine, a dihydropyridine calcium antagonist, selected as the poorly water-soluble model drug. To obtain active drug in stomach, duodenum and lower segment small intestine, respectively, polymers, i.e. Acrylic resins Eudragit E-100, Hydroxypropylmethylcellulose phthalate acetate succinate, were formulated to produce microspheres, which dissolve at an acid condition, pH ≥5.5 ≥6.5, respectively. The quasi-emulsion solvent diffusion method employed manufacturing process for All microspheres had highly spherical shape high incorporation efficiency (>91.0%). particle sizes mainly affected agitation speed temperature process. results X-ray diffraction suggested that nitrendipine molecularly dispersed amorphous state. dissolution behavior under simulated gastrointestinal conditions revealed obvious characteristics. profiles content systems stored 40 °C relative humidity 75% unchanged during 3-month period accelerating storage conditions. bioavailability testing six healthy dogs could improve efficiently uptake prolong T max value vivo.