Drug release factors affecting, examples

It may be necessary to consider the effect of a boundary layer on the release rate. A boundary layer of appreciable drug concentration on the surface of the device would hinder drug release by diffusion. The effect of the layer is more marked with drugs of low solubility and with microparticles having irregular surfaces. From this simple example, it can be seen that various factors affect the release rate from reservoir microcapsules. 

It is important to appreciate that predictive estimates are of limited value even when the estimates and assumptions within the model are rigorous. Many variables associated with actual product use will significantly alter the extent of skin penetration. For example, reapplication of a formulation, drug release from a formulation and the presence of inactive excipients may all affect skin permeability. If these complicating parameters could be factored into the overall calculations, then the predictive values could perhaps provide a closer approximation to the actual skin permeability under in-use conditions. 

Pharmaceutical factors. The amount of drug that is released from a dose form (and so becomes available for absorption) is referred to as its bioavailability. This is highly dependent on its pharmaceutical formulation. With tablets, for example, particle size (surface area exposed to solution), diluting substances, tablet size and pressure used in the tabletting machine can affect disintegration and dissolution and so the bioavailability of the drug. 

Irrespective of the chosen apparatus, the equipment must be set up and handled in a way that both minimises the variability of the dissolution and avoids artefacts. The most common source to such variability or artefacts is hydrodynamic factors, but unwanted chemical reactions or temperature shifts could also occur. Alterations of hydrodynamics, as well as changes of temperature, can both affect the dissolution of a drug substance and the release of a substance from the dosage form. Chemical reactions in the test medium may cause degradation of the drug substance or some formulation excipient which may affect the dissolution, or may lead to misinterpretation of the results. Examples of different sources to variability for the USP apparatuses are summarised below ... 

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