TY - JOUR
T1 - A novel pH-dependent gradient-release delivery system for nitrendipine
T2 - I. Manufacturing, evaluation in vitro and bioavailability in healthy dogs
AU - Yang, Mingshi
AU - Cui, Fude
AU - You, Bengang
AU - You, Jian
AU - Wang, Liang
AU - Zhang, Liqiang
AU - Kawashima, Yoshiaki
PY - 2004
Y1 - 2004
N2 - A novel pH-dependent gradient-release delivery system was developed by mixing three kinds of pH-dependent microspheres. Nitrendipine, a dihydropyridine calcium antagonist, was selected as the poorly water-soluble model drug. To obtain gradient-release of the active drug in the stomach, duodenum and lower segment of the small intestine, respectively, three kinds of pH-dependent polymers, i.e. Acrylic resins Eudragit E-100, Hydroxypropylmethylcellulose phthalate and Hydroxypropylmethylcellulose acetate succinate, were formulated to produce the microspheres, which dissolve at an acid condition, the pH of > or = 5.5 and > or = 6.5, respectively. The quasi-emulsion solvent diffusion method was employed in the manufacturing process for the microspheres. All three kinds of microspheres had a highly spherical shape and high incorporation efficiency (>91.0%). The particle sizes were mainly affected by the agitation speed and temperature of the manufacturing process. The results of X-ray diffraction suggested that nitrendipine in the microspheres was molecularly dispersed in an amorphous state. The drug dissolution behavior of the system under the simulated gastrointestinal pH conditions revealed obvious gradient-release characteristics. The dissolution profiles and content of the systems stored at a temperature of 40 degrees C and a relative humidity of 75% were unchanged during a 3-month period of accelerating storage conditions. The results of the bioavailability testing in six healthy dogs suggested that the pH-dependent gradient-release delivery system could improve efficiently the uptake of the poorly water-soluble drug and prolong the Tmax value in vivo.
AB - A novel pH-dependent gradient-release delivery system was developed by mixing three kinds of pH-dependent microspheres. Nitrendipine, a dihydropyridine calcium antagonist, was selected as the poorly water-soluble model drug. To obtain gradient-release of the active drug in the stomach, duodenum and lower segment of the small intestine, respectively, three kinds of pH-dependent polymers, i.e. Acrylic resins Eudragit E-100, Hydroxypropylmethylcellulose phthalate and Hydroxypropylmethylcellulose acetate succinate, were formulated to produce the microspheres, which dissolve at an acid condition, the pH of > or = 5.5 and > or = 6.5, respectively. The quasi-emulsion solvent diffusion method was employed in the manufacturing process for the microspheres. All three kinds of microspheres had a highly spherical shape and high incorporation efficiency (>91.0%). The particle sizes were mainly affected by the agitation speed and temperature of the manufacturing process. The results of X-ray diffraction suggested that nitrendipine in the microspheres was molecularly dispersed in an amorphous state. The drug dissolution behavior of the system under the simulated gastrointestinal pH conditions revealed obvious gradient-release characteristics. The dissolution profiles and content of the systems stored at a temperature of 40 degrees C and a relative humidity of 75% were unchanged during a 3-month period of accelerating storage conditions. The results of the bioavailability testing in six healthy dogs suggested that the pH-dependent gradient-release delivery system could improve efficiently the uptake of the poorly water-soluble drug and prolong the Tmax value in vivo.
KW - Acrylates
KW - Administration, Oral
KW - Animals
KW - Biological Availability
KW - Delayed-Action Preparations
KW - Dogs
KW - Drug Carriers
KW - Drug Stability
KW - Hydrogen-Ion Concentration
KW - Male
KW - Methylcellulose
KW - Microscopy, Electron, Scanning
KW - Microspheres
KW - Nitrendipine
KW - Particle Size
KW - Polymers
KW - X-Ray Diffraction
U2 - 10.1016/j.jconrel.2004.04.022
DO - 10.1016/j.jconrel.2004.04.022
M3 - Journal article
C2 - 15262414
SN - 0168-3659
VL - 98
SP - 219
EP - 229
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 2
ER -