Effects of shear and pH on starch phosphates prepared by reactive extrusion as a sustained release agent
2009
O’Brien, Stephen | Wang, Ya-Jane
Characteristics of native starch have limited its application in solid dosage forms as a sustained release agent. There is a growing interest in improving starch functionality for sustained release applications because of its biocompatibility and biodegradability. This study investigated the effects of different shear and pH conditions on starch extrudates prepared via reactive extrusion to act as an excipient in sustaining drug release. Starches, including waxy corn, common corn, and potato, were used to prepare starch phosphates at a shear rate of 50 or 200 rpm and at pH 9.0 or 11.0. The reaction efficiency of phosphorylation was improved when extruded at 200 rpm. Unmodified starch extrudates exhibited more degradation at 200 rpm with a shorter residence time over those at 50 rpm with a longer residence time. The carbohydrate profiles of starch phosphates showed an increased proportion of high molecular-weight components at 200 rpm, possibly due to an increase in cross-linking reaction at a higher shear rate. Both waxy corn and potato phosphates exhibited an n value indicative of anomalous transport, but most common corn phosphates showed an n value indicative of Fickian diffusion. Waxy corn phosphates exhibited different rheological properties but similar drug release profiles. Common corn phosphates exhibited rigid gel conformations, and exhibited slower drug release than unmodified ones. Potato starch phosphates exhibited considerable differences in their rheological properties drug release profiles between 50 and 200 rpm with phosphates at 200 rpm showing more fluid-like properties and poor drug release. The results demonstrate that the reaction efficiency of phosphorylation by reactive extrusion and subsequently drug release can be affected by the shear rate and pH for different starch types.
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