Mechanistic investigation of drug release from asymmetric membrane tablets: effect of media gradients (osmotic pressure and concentration), and potential coating failures on in vitro release.

Purpose: An asymmetric membrane (AM) tablet was developed for a soluble model compound to study the in vitro drug release mechanisms in challenge conditions, including osmotic gradients, concentration gradients, and under potential coating failure modes. Porous, semipermable membrane integrity may be compromised by a high fat meal or by the presence of a defect in the coating that could cause a safety concern about dose-dumping.

Methods: The osmotic and diffusional release mechanisms of the AM tablet were independently shut down such that their individual contribution to the overall drug release was measured.

A thermodynamic model for organic and aqueous tablet film coating.

A tablet film-coating model for aqueous- and/or organic-based systems is shown to predict exhaust stream conditions thereby facilitating process optimization and scale-up. This coating model uses the First Law of Thermodynamics and conservation of mass principles to complete a material-energy balance on the coating unit operation for a closed, non-isolated system. Heat loss from the coating pan is incorporated into the model through a parameter called a heat loss factor (HLF) that is directly related to the heat transfer coefficient and pan surface area.