Preparation and in vitro evaluation of a novel combined multiparticulate delayed-onset sustained-release formulation of diltiazem hydrochloride.
A combined delivery system, containing two kinds of diltiazem hydrochloride multi-layer coated pellets with different release characteristics, was developed to meet chronotherapeutic requirements. The dissolution studies in vitro indicated that the combined system could constantly release drug at a predetermined time in synchrony with the biologic rhythm of disease activity. These two kinds of pellets were mixed at the ratio 1:1. Pellet 2 could provide drug during the later phase of drug release from pellet 1, because the amount released was insufficient in the later phase (about 14-24 h after administration) for pellet 1. Addition of Tween 20 in the HPMC swelling layer was able to modify the hydration rate of HPMC layer which controlled the delayed time of the release system. It was found that the drug release kinetics followed Hixson-Crowell equation and this indicated that the main drug-transport mechanism inside the pellets was an erosion mechanism. The drug release rate was independent of the hydrodynamic conditions and pH of the external environment, and showed a decrease with increasing of osmotic pressure of the dissolution medium. These release characteristics indicated that the drug release from this system was driven by osmotic-pressure gradient.
Chen
Shengjun
S
Department of Pharmaceutics, China Pharmaceutical University; 24 Tong Jia Xiang, Nanjing 210009, PR China. chensjxz1123@163.com
Zhu
Jiabi
J
Cheng
Ji
J
D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000737:chemistry; D003692:Delayed-Action Preparations; D004110:Diltiazem / Q000008:administration & dosage* / Q000737:chemistry; D004339:Drug Compounding; D005079:Excipients; D006863:Hydrogen-Ion Concentration; D065347:Hypromellose Derivatives; D007700:Kinetics; D016014:Linear Models; D008747:Methylcellulose / Q000031:analogs & derivatives; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D008956:Models, Chemical; D009997:Osmotic Pressure; D010316:Particle Size; D011136:Polysorbates; D012995:Solubility
D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D005079:Excipients; D011136:Polysorbates; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D004110:Diltiazem