Rate-controlled release, dispersed system

Matrix diffusion-controlled system in which the drug is homogeneously dispersed in a hydrophilic polymer diffusion from the matrix controls release rate Nitrodur (nitroglycerin key). 

In comparison with previous studies, the systems studied by Pays et al. possess the advantage of being size-controlled and reproducible. This is an important property because, as demonstrated by the authors, the rate of release of double emulsions is strongly dependent on the colloidal size of the dispersed objects. The following notations are used to characterize the composition and properties of double emulsions ... 

Currently, most mature dissolution controlled release systems/ technologies are applicable for water-soluble and low-water-solubility compounds (with low doses). For very poorly water-soluble compounds, dissolution controlled release systems/technologies may not be applicable because these compounds have intrinsically slow dissolution/release rates. Recently, several new technologies such as solid dispersions and self-emulsifying drug delivery systems (SEDDS) have been developed to deliver poorly water-soluble compounds at reasonable doses through enhancement of dissolution rate. These technologies have created new potentials for controlled release of poorly water-soluble compounds, often... 

Diffusion-controlled devices may be designed for continuous release and usually use either a matrix or reservoir construction. In matrix systems, the drug is dispersed randomly throughout a polymer, whereas reservoir devices surround the drug with an intact rate-controlling membrane. Regardless of the method of construction, the system must be safe and biocompatible for biological application. 

The microsealed delivery device is a variation of the matrix-type transdermal system in which the drug is dispersed in a reservoir phase which is then immobilized as discrete droplets in a cross-linked polymeric matrix. Release can be further controlled by inclusion of a polymeric microporous membrane. This system therefore combines the principles of both the liquid reservoir and matrix-type devices. Rate of release of a drug from a microsealed delivery system is dependent on the partition coefficient between the reservoir droplets and the polymeric matrix the diffusivity of the drug in the reservoir, the matrix and the controlling membrane and on the solubility of the drug in the various phases. There are, obviously, many ways to achieve the desired zero-order release rate, but only nitroglycerin has been commercially formulated into this type of delivery device (Karim 1983). 

In a matrix dispersion system the active substance is in the polymer matrix reservoir in a dispersed (dissolved or suspended) state and diffusion is controlled by the structure of the matrix. The rate of release is described by a relationship similar to (16.7) Higuschi s equation [59] ... 

Ozeki, T. Yuasa, H. Kanaya, Y Oishi, K. Application of the solid dispersion method to the controlled release of medicine. V. Suppression mechanism of the medicine release rate in the three-component solid dispersion system. Chem. Pharm. Bull. 1994, 42 (2), 337-343. 

It is also important to note that each of these dispersions can be exploited to enhance the delivery of the drug substance. For example, the majority of dissolution enhanced products are prepared in the amorphous state to leverage the higher solubility of the material and increase release rates from the drug product. Furthermore, the homogeneous nature of the dispersion provides a kinetic barrier for recrystallization of the amorphous form that contributes to improved physical stability. However, in the case of controlled release and directly shaped products where the systems may be prepared to have specific structural and mechanical attributes, the use of solid dispersions wherein both the drug and polymer exist as crystalline materials within the system may be beneficial. 

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