Starch phosphates prepared by reactive extrusion as a sustained release agent

Abstract

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 non-toxicity and biodegradability. This study attempted to investigate extruded starch phosphates as an excipient in sustaining drug release. Starches from various botanical sources with different amylose contents, including waxy corn, common corn, Hylon V (∼50% amylose), Hylon VII (∼70% amylose), and potato, were used to prepare starch phosphates at pH 9.0 or 11.0 using a reactive extrusion method. Phosphorous content was higher for starch phosphates prepared at pH 9.0 than at pH 11.0, and varied with starch type when phosphorylated at pH 9.0. Reactive extrusion produced starch extrudates that upon forming hydrogels were capable of sustaining release of metoprolol tartrate (MPT). The structural features of the hydrogel as modified by the phosphorylation reaction were found to alter the kinetics of drug release from the swellable matrices. The unmodified extrudates formed weaker gels as evidenced by their rheological properties, and showed faster drug release. Waxy corn starch phosphorylated at pH 9.0 as well as common corn and potato starches phosphorylated at pH 11.0 were found to exhibit more case-II-like properties attributed to a high density of cross-links and stronger chain entanglement. Waxy corn starch phosphorylated at pH 9.0 exhibited the lowest degree of drug release. The entanglement among amylopectin molecules and branch chains was suggested to play a role in governing MPT release.