Soy Matrix Drug Delivery Systems Obtained by Melt-Processing Techniques

Abstract

The aim of this study was to develop new soy protein drug delivery matrix systems by melt-processing techniques, namely, extrusion and injection moulding. The soy matrix systems with an encapsulated drug (theophylline, TH) were previously compounded by extrusion performed at two different pH values, (i) pH 4 (SIpDtp) and (ii) pH 7 (SIDtp), and further injection-moulded into a desired shape. During the extrusion process the matrixes SIDtp were also cross-linked with glyoxal (0.6X-SIDtp) and reinforced with a bioactive filler, hydroxylapatite (SI-HADtp). The obtained mouldings were used to study the drug-release mechanisms from the plastic soy-TH matrixes. In an isotonic saline solution (ISS) buffered at pH 5.0 (200 mM acetate buffer), the resulting release kinetics could be described using the Fick's second law of diffusion. Because the diffusion coefficients were found to be constant and the boundary conditions to be stationary, these systems are drug-diffusion controlled. Conversely, the dominant phenomena in an isotonic saline solution buffered at pH 7.4 (200 mM Tris/HCl buffer) are more complex. In fact, because of the higher polymer solubility, the resulting matrix is time-variant. So, the drug release is affected by swelling, drug diffusion, and polymer dissolution, being faster when compared to ISS-200 mM acetate buffer, pH 5.0. The changes in the formulation composition affecting the correspondent release rates were also investigated. At pH 7.4, increasing the cross-linking degree of the polymer matrix (via reaction with glyoxal or heat treatment) or decreasing the net charge (extruding at pH near its isoelectric point) led to lower release rates. The incorporation of ceramic filler caused the opposite effect. Because of the low solubility of the matrix at pH 5.0, no significant variations were detected with variations in the selected formulations. These systems, based on a nonstandard protein-based material, seem to be very promising to be used as carriers for drug delivery.

Controlled Delivery Achieved with Bi‐Layer Matrix Devices Produced by Co‐Injection Moulding

“…As reported in a previous study, [33] the hydroxylapatite tends to suffer a partial dissolution when in contact with the release media, thus increasing the matrix porosity. Due to the increased interfacial area, it is expected that when the drug reaches this layers it would diffuse faster than it would in SI, increasing as desired the release rate.…”

“…The investigated drug containing SID tp and 0.6X-SID tp matrices were used as the drug-containing inner layers to provide both slow release (in acidic surroundings) and fast release (in neutral surroundings). [33] In order to further hinder drug diffusion out of the device, a soy protein-based drug-free outer layer was used. The crosssections of the bi-layer devices can be seen in Figure 2.…”

“…Furthermore, the bi-layer device with the crosslinked core (SI s /0.6X-SID c ) proved to be even more efficient than the bilayer device SI s /SID c on decreasing the total release rates. This fact must relate with: i) difference in core's crosslinking density and respective solubility as a function of pH ( Figure 4); [33] and ii) difference in skin's thickness ( Figure 2). In fact, the skin/core ratio of the system SI s / 0.6X-SID c is higher than that of SI s /SID c , assuming the respective values of 0.33 AE 0.07 and 0.11 AE 0.04.…”

pH‐sensitive alginate/soy protein microspheres as drug transporter

“…A wide range of biocompatible natural polymers such as polysaccharides and proteins, such as chitosan, 1 alginate (AL), 2 cellulose, 3 soy protein, 4 zein, 5 casein, 6 and so on, are potentially available as the biomedical materials, 7 and especially has been developed as the carrier of oral drugs. Microspheres are currently a typical form of drug carrier.…”

“…5 In addition, the bioactivity of other components in microspheres may facilitate the curative effect or reduce the side effect of drugs. 4 Especially, the miscible blends can be used to adjust the behavior of drug release depending on the properties of components as well as the compositions in whole blend and the interaction between components, and especially produced the function of the pulsatile chronotherapeutics and the controlled profiles of drug release. 11 Biocompatible ALs can be ionically crosslinked in the presence of multivalent cations 12 and induced the gelation, which was already used to produce many kinds of biomedical materials, such as hydrogel, 13 microcapsule, 14 microsphere, 5,[8][9][10] membrane, 15 and fiber.…”