A novel time-controlled release system based on drug-resin complexes and elementary osmotic pump.
A novel time-controlled system based on elementary osmotic pump tablet containing a drug-resin complexes (DRCs) core is presented. In the traditional osmotic pump tablets (OPTs), the lag time was always minimized. On the contrary, in the DRCs osmotic pump tablet (DRCOPT), the lag time was increased to achieve time-controlled delivery. The system led to a zero-order drug release after an initial lag time. Polyethylene oxide (PEO) N80 was used as suspension agent and NaCl was applied as ion-exchange, osmotic pressure (electrolyte supplementary) agent, respectively. To examine the mechanism of this system, drug release behaviors were investigated under conditions of various osmotic pressures. A new method of combination of conductivity and HPLC was applied to determine the different fractions of NaCl in producing osmotic pressure, ion-exchange and electrolyte supplement. The pharmacokinetic studies conducted in beagle dogs showed that a steadier and controlled drug release behavior was obtained compared with the traditional formulations. On the basis of prescription of the DRCOPT, a good in-vitro-in-vivo correlation (IVIVC, R(2)=0.9541) was achieved. In addition, a lag time of 4 h was observed in in vivo experiment, which indicated that the DRCOPT can be used in therapeutic regimens with the characteristics of chronotherapy.
Wang
Chao
C
Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Liaoning, PR China.
Chen
Fei
F
Heng
Paul Wan Sia
PW
Li
Ji-Zhong
JZ
Li
Xiang
X
Ye
Guan-Hao
GH
Nie
Shu-Fang
SF
Pan
Wei-San
WS
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics; D000465:Algorithms; D000818:Animals; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004285:Dogs; D004553:Electric Conductivity; D009995:Osmosis; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011433:Propranolol / Q000008:administration & dosage / Q000493:pharmacokinetics; D012117:Resins, Synthetic / Q000737:chemistry; D012965:Sodium Chloride; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013607:Tablets
D000319:Adrenergic beta-Antagonists; D003692:Delayed-Action Preparations; D004364:Pharmaceutical Preparations; D012117:Resins, Synthetic; D013607:Tablets; D011092:Polyethylene Glycols; D012965:Sodium Chloride; D011433:Propranolol