Zero-order release kinetics from a self-correcting floatable asymmetric configuration drug delivery system.

A new approach based on the three-layer matrix technology to control drug release for oral administration is presented. Polyethylene oxide polymers of various molecular weight together with theophylline as drug model and other excipients have been directly compressed into a three-layer asymmetric floatable system. The core layer contains the active drug while external layers with different thickness, composition, and erosion rates are designed to delay the hydration of the middle layer, restrict the early drug diffusion only through cylindrical side surfaces of the tablet, and provide controlled drug release. Results show that during a 16 h dissolution study drug is completely released following the zero-order kinetics with no burst effect. The release rate remains around 0.1 mg min-1 throughout the dissolution study. The release kinetics is independent of changes in pH and compression force but dependent on layer thickness and formulation components. It appears that the operating release mechanism is based on the existence of a balance between the velocities of advancing glassy/rubbery front and erosion at the swollen polymer/dissolution front.

[1]  W. Ritschel,et al.  Multiple-layer, direct-compression, controlled-release system: in vitro and in vivo evaluation. , 1993, Journal of pharmaceutical sciences.

[2]  G. C. Sarti,et al.  Solvent osmotic stresses and the prediction of Case II transport kinetics , 1979 .

[3]  N. Peppas,et al.  Swelling characteristics of hydrophilic matrices for controlled release New dimensionless number to describe the swelling and release behavior , 1992 .

[4]  Paolo Colombo,et al.  Swelling-controlled release in hydrogel matrices for oral route , 1993 .

[5]  A La Manna,et al.  Swelling-activated drug delivery systems. , 1988, Biomaterials.

[6]  H. Hopfenberg,et al.  Swelling‐controlled, constant rate delivery systems , 1978 .

[7]  W. Erni,et al.  The hydrodynamically balanced system: a novel principle of controlled drug release. , 1987, European neurology.

[8]  A Apicella,et al.  Poly(ethylene oxide) (PEO) and different molecular weight PEO blends monolithic devices for drug release. , 1993, Biomaterials.

[9]  C J Kim,et al.  Drug release from compressed hydrophilic POLYOX-WSR tablets. , 1995, Journal of pharmaceutical sciences.

[10]  Paolo Colombo,et al.  Multi-layered hydrophilic matrices as constant release devices (GeomatrixTM Systems) , 1993 .

[11]  M. H. Rubinstein,et al.  Formulation of sustained release promethazine hydrochloride tablets using hydroxypropyl-methylcellulose matrices , 1985 .

[12]  Paolo Colombo,et al.  Drug release modulation by physical restrictions of matrix swelling , 1990 .

[13]  N. Peppas Analysis of Fickian and non-Fickian drug release from polymers. , 1985, Pharmaceutica acta Helvetiae.

[14]  G. C. Sarti,et al.  Diffusion and localized swelling resistances in glassy polymers , 1982 .

[15]  G. C. Sarti,et al.  Effect of the thermal histories on case II sorption kinetics: Test of a kinetic theory for swelling , 1984 .