Critical Points in Hydrophilic Matrices

As it has been explained in the previous section, the percolation theory has been extensively employed to describe the behavior of inert matrix systems. More recently, this theory has been applied to the study of swellable matrices being critical points in hydrophilic matrices reported for the first time by Caraballo and Leuenberger in 2004 [92]. An important number of papers dealing with the application of the percolation theory to the study of the release and the water uptake behavior of these systems 

The presence of critical points supposes a discontinuity of the system due to the geometrical phase transition that takes place. This leads to a different distribution of the components of the system. In the case of swellable matrices, critical points can be expected for each one of the components of the formulation. Nevertheless, it has been proved that the polymer critical point plays the most important role in these systems. Above the polymer percolation threshold, this excipient, in contact with the biological fluids, forms a coherent gel layer that acts by controlling the drug release rate. On the contrary, below the polymer percolation threshold, polymer is distributed in isolated clusters which do not produce a continuous gel layer. This leads to the erosion of the polymer and in the majority of the cases to the disintegration of the matrix, with the subsequent abrupt release of the drug in a similar way as a conventional dosage form [60]. 

With respect to the drug percolation threshold, this critical point shows much less influence on the behavior of hydrophilic matrices when compare to inert matrix tablets. This is attributed to the fact that in swellable matrices the existence of an infinite cluster of drug is not necessary to obtain its complete release. In these systems the polymer swells and enables the water penetration through the whole systems without the need of a percolating cluster of soluble substances. Therefore, little differences have been found between matrices formulated below and above the drug percolation threshold [13,93,96]. 

In Section 4.6.1.3 it has been explained the existence of a combined percolation threshold in inert matrices, which supposes that this percolation threshold can be reached independently of the proportion of each polymer in the blend with the condition that 

In this study, the percolation threshold of HPMC and NaCMC binary matrices were estimated analyzing the water uptake and the release behavior of the matrices. Ihe HPMC percolation threshold was situated between 29 and 41% (v/v) HPMC for the binary KCl-HPMC matrices, while the excipient percolation threshold for the binary KCl-NaCMC hydrophihc matrices was found between 39 and 54% (v/v) NaCMC. As it can be appreciated, there is a narrow range of overlapping concentrations for the polymers percolation threshold. Thus it suggests that there is a small possibility that these two polymers can show a combined percolation threshold. This hypothesis is confirmed since considerable differences in the Higuchi s slope values (1.416 and 0.49, respectively) were found in two batches of matrices prepared employing very similar volume percentages of both polymers. 

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