(660c) Model Development and Experimental Validation for Predicting Drug Release in Bilayer Osmotic Tablets

The Controlled Release System can be categorized into four broad types, which include the following: i) Chemically Controlled, ii) Diffusion Controlled, iii) Osmotically Controlled and iv) Swelling-and/or Dissolution controlled. Amongst these mechanisms, the Oral Osmotic pump (OROS) tablet, wherein the drug release is controlled by the osmotic pressure gradient, offers an advantage over other drug delivery systems. These advantages include, lower incidence of adverse reactions, better compliance, reduced dosage necessary, independent of the hydrodynamic condition, gastric pH and agitation. In addition, various designs are available for such osmotic driven systems, so that a newer delivery design can be developed faster once the release mechanism is clearly understood.

Within the confines of orally administered osmotic pumps, the initial pump was the Extrudable core system (ECS), also conventionally known as elementary osmotic pump (EOP). The advantage of an ECS is that it is easy to prepare, and it can deliver water-soluble drugs at near zero-order rates. ECS is inherently disadvantaged as it cannot deliver water-insoluble drugs once the osmotic agent is completely extruded. Consequently, the drug remains within the tablet due to insufficient osmotic pressure generated by low solubility drugs. This problem of incomplete extrusion is solved by a bilayer system (push-pull system) also known as Swellable core technology (SCT) which ensures maximum extrusion.

In this work, we have developed a model of a bilayer osmotic controlled-release tablet that can predict the drug release rate with high accuracy as a function of various key parameters. These parameters are of critical importance, consisting of the coating thickness & the tablet size as well as the excipients and the active pharmaceutical ingredient. The aim is to understand the drug release process better so that high doses of water-insoluble (low solubility) drugs can be delivered efficiently at a controlled rate. The model describes dynamically all the main release processes occurring during the dissolution of a tablet coated with a semi-permeable membrane, namely, the solvent influx driven by the difference in osmotic pressure across the coating in both drug and sweller layer, dispersion of core components (drug and polymer), swelling of the tablet due to solvent accumulation, build-up of hydrostatic pressure inside the tablet, tensile stress acting on the coating, and the efflux of the dispersed core components, dissolution of drug particles in bulk, swelling of the polymer in the sweller layer, and pressure exerted by sweller layer onto the drug layer. The model was validated by comparing the predictions with drug release data for two drugs with varying solubilities and for the same drug in different dissolution media. The predictions of drug release from SCT tablets are in good agreement with the measurements, suggesting that our model is well suited for elucidating the osmotically controlled drug release from SCT tablets.