In the case of matrices consisting of a swelling hydrophilic polymer, the penetration of the dissolution fluid into the system gives rise to a polymer phase transition from glassy to rubbery state. This transition implies a distension of the polymeric chains which acquire great mobility and the formation of an increasing layer of gelled polymer. Diffusion of the active principle molecules takes place through the gelled layer, whereas this does not occur in the glassy state. The release kinetic of this matrix system is mainly related to diffusion, besides swelling and erosion. In most cases, release rate is a function of the square root of time and therefore tends to decrease as the thickness of the gelled polymeric layer and hence the thickness of the layer that the drug must cross in order to reach the dissolution fluid, increases with the time. A remarkable increase of the external surface of the system occurs because of the swelling and this effect contributes to increase the release rate. Nevertheless the overall observed result is a decreased drug release rate, more and more significant as the end of the release process is approached because of the prevailing effect of the increasing thickness of the gelled layer with the time.
Conventional matrix systems release the active principle more slowly and at a decreasing rate. They consequently do not overcome the disadvantages of traditional pharmaceutical forms, such as a peak of hematic concentration, followed by a relatively sudden fall.
There have been attempts to overcome these drawbacks, which are typical of hydrophilic matrices and related to a non-linear release kinetic. For example, in U.S. Pat. No. 4,839,177, a system is described which consists of a nucleus containing the drug and swelling polymer, having a defined shape, with an insoluble coating on one or more of its faces. The purpose of the coating is to modulate the swelling of the polymer so as to obtain a constant drug release. The system releases the drug with a constant kinetic only in cases where a base or the lateral surface are coated so as to delimit the releasing area. Moreover, the linear kinetic release is obtained only by using soluble polymers.
USPTO Backgrounds
USPTO Backgrounds