Soy matrix drug delivery systems obtained by melt-processing techniques.
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.
Vaz
Cláudia M
CM
Department of Polymer Engineering, University of Minho, Campus de Azurém, 4800-058 Guimarães, Portugal. c.m.vaz@tue.nl
van Doeveren
Patrick F N M
PF
Reis
Rui L
RL
Cunha
António M
AM
D001672:Biocompatible Materials / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D006863:Hydrogen-Ion Concentration; D008422:Materials Testing; D030262:Soybean Proteins / Q000627:therapeutic use*; D013806:Theophylline / Q000008:administration & dosage
D001672:Biocompatible Materials; D004337:Drug Carriers; D030262:Soybean Proteins; D013806:Theophylline