(198g) Model Development and Experimental Validation for Predicting Drug Release in Single-Layer 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. Despite the large number of experimental studies on oral osmotic drug delivery systems, few have modelled the details of the drug release process.

In the present work, a single-layered osmotic controlled release tablet, which is conventionally also known as an Extrudable Core System (ECS), is modelled to accurately predict the drug release rate as a function of several key parameters. These include the excipients and the active pharmaceutical ingredient, the coating thickness as well as the geometry of the tablet. The model elucidates the key events occurring during the dissolution of a tablet, which is coated with a semi-permeable membrane. These events include, the solvent influx, which is driven by the osmotic pressure differences across the coating, core component (drug, polymer and osmogen) dispersion, tablet swelling due to the solvent accumulation, the hydrostatic pressure build up within, tensile stresses acting on the coating, the extrusion of the dispersed core components and dissolution of the drug particles in bulk. Additionally, the condition for successful entrainment of the drug particles based on the hydrated phase viscosity and other parameters has been derived. The model is validated by comparing the predictions with drug release data for two drugs with varying solubilities. The predicted release and the measured release are in good agreement, which confirms the accuracy of our model for describing the osmotically controlled drug release process from ECS tablets.

The attached figure compares the predicted drug release profile with measurements, (a) Effect of osmogen concentration on drug release, and (b) Effect of coating thickness on drug release. The solid lines are model predictions while the symbols represent measurements.