6%), this barrier appears to be BMS907351 strong enough to allow this linear behavior until the release of all the encapsulated drug amount. However, for intermediate concentrations (as observed in Figure 3 cases 2 and 5.5%), after a given time tα, this diffusion-limiting layer is dissolved or disaggregated, and a second phase of drug release occurs. This phase follows a “nonsteady state” diffusion regime for which the concentration gradient varies with time. This process is described

in the general case by the Fick’ second law, reported below: dCdt=Dd2Cdx2. (3) Inhibitors,research,lifescience,medical In the case of a spherical drug delivery matrix, this equation is adapted as shown below: MtM∞=6(D(t−tα)πR2)1/2−3D(t−tα)R2  , (4) where M∞ is the mass of the drug released at infinite time, tα is the delay induced by the first zero-order release, and R is the sphere radius. This behavior

is also found for the noncoated tablets, Inhibitors,research,lifescience,medical with a lag time tα around 19 seconds due to the tablet hydration. It is interesting to note that the zero-order release profiles exhibit slopes (i.e., release speeds quantified below), decreasing with increasing amount of coating lipid. This detail confirms that the diffusion-based mechanism can be a correct interpretation of the zero-order phenomena compared to the other physical possible processes, for example, zero-order homogeneous erosion for which the release speed should be constant in similar Inhibitors,research,lifescience,medical experimental conditions. All the release profiles of the formulation (B) are fitted following these two models, and schematic illustrations of the mechanisms and tablets structures are reported in Figure 6. Figure 6 Interpretations of the drug release behaviors from Figure 3. Theophylline release Inhibitors,research,lifescience,medical from tablets (b), for different levels of nanoemulsion coating: 2%, 5.5%, 6%, and 7.6%, and noncoating tablets. The main results of a quantitative comparison of the different cases are reported in Table 3. Table 3 Experimental parameters obtained from the kinetics drug release Inhibitors,research,lifescience,medical of tablets (B) (see Figure 6). The release speeds reported (dMt/dt) correspond to the linear diffusion regime. The theoretical models appear

quite well in accordance with experimental results, which confirms the hypothesis ventured regarding the structures and the release processes. The higher Dipeptidyl peptidase the nanoemulsion coating level, the lower the release speed. If the coated lipid layer is considered globally constant, this behavior can be attributed to the decrease of the diffusion coefficient D, and thus to the decrease of the permeability P = DK/(Re − Ri). On the other hand, the time tα in which this lipid layer is broken up also appears related to the coating amount. It follows therefrom that tα indicates the transition between the two diffusion regimes (1) and (2) highlighted in Figure 6. The higher the coating amount, the more stable is the layer, being definitively stable for the examples of 6 and 7wt.%.