Preparation and in vitro evaluation of a novel combined multiparticulate delayed-onset sustained-release formulation of diltiazem hydrochloride. 2007

Shengjun Chen, and Jiabi Zhu, and Ji Cheng
Department of Pharmaceutics, China Pharmaceutical University; 24 Tong Jia Xiang, Nanjing 210009, PR China. chensjxz1123@163.com

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.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008747 Methylcellulose Methylester of cellulose. Methylcellulose is used as an emulsifying and suspending agent in cosmetics, pharmaceutics and the chemical industry. It is used therapeutically as a bulk laxative. BFL,Celevac,Cellothyl,Cellulone,Citrucel,Cologel,Dacryolarmes,Methocel,Methyl Cellulose,Muciplasma,Cellulose, Methyl
D008855 Microscopy, Electron, Scanning Microscopy in which the object is examined directly by an electron beam scanning the specimen point-by-point. The image is constructed by detecting the products of specimen interactions that are projected above the plane of the sample, such as backscattered electrons. Although SCANNING TRANSMISSION ELECTRON MICROSCOPY also scans the specimen point by point with the electron beam, the image is constructed by detecting the electrons, or their interaction products that are transmitted through the sample plane, so that is a form of TRANSMISSION ELECTRON MICROSCOPY. Scanning Electron Microscopy,Electron Scanning Microscopy,Electron Microscopies, Scanning,Electron Microscopy, Scanning,Electron Scanning Microscopies,Microscopies, Electron Scanning,Microscopies, Scanning Electron,Microscopy, Electron Scanning,Microscopy, Scanning Electron,Scanning Electron Microscopies,Scanning Microscopies, Electron,Scanning Microscopy, Electron
D008863 Microspheres Small uniformly-sized spherical particles, of micrometer dimensions, frequently labeled with radioisotopes or various reagents acting as tags or markers. Latex Beads,Latex Particles,Latex Spheres,Microbeads,Bead, Latex,Beads, Latex,Latex Bead,Latex Particle,Latex Sphere,Microbead,Microsphere,Particle, Latex,Particles, Latex,Sphere, Latex,Spheres, Latex
D008956 Models, Chemical Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment. Chemical Models,Chemical Model,Model, Chemical
D009997 Osmotic Pressure The pressure required to prevent the passage of solvent through a semipermeable membrane that separates a pure solvent from a solution of the solvent and solute or that separates different concentrations of a solution. It is proportional to the osmolality of the solution. Osmotic Shock,Hypertonic Shock,Hypertonic Stress,Hypotonic Shock,Hypotonic Stress,Osmotic Stress,Hypertonic Shocks,Hypertonic Stresses,Hypotonic Shocks,Hypotonic Stresses,Osmotic Pressures,Osmotic Shocks,Osmotic Stresses,Pressure, Osmotic,Pressures, Osmotic,Shock, Hypertonic,Shock, Hypotonic,Shock, Osmotic,Shocks, Hypertonic,Shocks, Hypotonic,Shocks, Osmotic,Stress, Hypertonic,Stress, Hypotonic,Stress, Osmotic,Stresses, Hypertonic,Stresses, Hypotonic,Stresses, Osmotic
D010316 Particle Size Relating to the size of solids. Particle Sizes,Size, Particle,Sizes, Particle
D011136 Polysorbates Sorbitan mono-9-octadecanoate poly(oxy-1,2-ethanediyl) derivatives; complex mixtures of polyoxyethylene ethers used as emulsifiers or dispersing agents in pharmaceuticals. Polysorbate,Polysorbate 20,Polysorbate 80,Sorbitan Derivatives,Tween,Tweens,PSML,Polyoxyethylene Sorbitan Monolaurate,Tween 20,Tween 60,Tween 80,Tween 81,Tween 85,20s, Polysorbate,20s, Tween,60s, Tween,80s, Polysorbate,80s, Tween,81s, Tween,85s, Tween,Derivative, Sorbitan,Derivatives, Sorbitan,Monolaurate, Polyoxyethylene Sorbitan,Monolaurates, Polyoxyethylene Sorbitan,PSMLs,Polyoxyethylene Sorbitan Monolaurates,Polysorbate 20s,Polysorbate 80s,Sorbitan Derivative,Sorbitan Monolaurate, Polyoxyethylene,Sorbitan Monolaurates, Polyoxyethylene,Tween 20s,Tween 60s,Tween 80s,Tween 81s,Tween 85s
D002121 Calcium Channel Blockers A class of drugs that act by selective inhibition of calcium influx through cellular membranes. Calcium Antagonists, Exogenous,Calcium Blockaders, Exogenous,Calcium Channel Antagonist,Calcium Channel Blocker,Calcium Channel Blocking Drug,Calcium Inhibitors, Exogenous,Channel Blockers, Calcium,Exogenous Calcium Blockader,Exogenous Calcium Inhibitor,Calcium Channel Antagonists,Calcium Channel Blocking Drugs,Exogenous Calcium Antagonists,Exogenous Calcium Blockaders,Exogenous Calcium Inhibitors,Antagonist, Calcium Channel,Antagonists, Calcium Channel,Antagonists, Exogenous Calcium,Blockader, Exogenous Calcium,Blocker, Calcium Channel,Blockers, Calcium Channel,Calcium Blockader, Exogenous,Calcium Inhibitor, Exogenous,Channel Antagonist, Calcium,Channel Blocker, Calcium,Inhibitor, Exogenous Calcium
D003692 Delayed-Action Preparations Dosage forms of a drug that act over a period of time by controlled-release processes or technology. Controlled Release Formulation,Controlled-Release Formulation,Controlled-Release Preparation,Delayed-Action Preparation,Depot Preparation,Depot Preparations,Extended Release Formulation,Extended Release Preparation,Prolonged-Action Preparation,Prolonged-Action Preparations,Sustained Release Formulation,Sustained-Release Preparation,Sustained-Release Preparations,Timed-Release Preparation,Timed-Release Preparations,Controlled-Release Formulations,Controlled-Release Preparations,Extended Release Formulations,Extended Release Preparations,Slow Release Formulation,Sustained Release Formulations,Controlled Release Formulations,Controlled Release Preparation,Controlled Release Preparations,Delayed Action Preparation,Delayed Action Preparations,Formulation, Controlled Release,Formulations, Controlled Release,Prolonged Action Preparation,Release Formulation, Controlled,Release Formulations, Controlled,Sustained Release Preparation,Timed Release Preparation,Timed Release Preparations

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