Development and characterization of new functionalized polyurethanes for sustained and site-specific drug release in the gastrointestinal tract.

The main objective of the present paper has been the development and study of two new biodegradable polyurethanes, PU(dithiodiethanol-DTDI) and PU[((i)Pr)Man-DTDI], to be used as sustained matrix forming excipients. Furthermore, their capacity to act as excipient for colon drug delivery systems has been evaluated. Thus, SeDeM diagrams have been obtained to investigate their suitability to be processed through a direct compression process. Matrices containing 10-30% w/w of the polymers and theophylline anhydrous as model drug have been manufactured. Release studies have been carried out using a modified dissolution assay simulating pH and redox conditions for the gastro intestinal tract, including colon. Drug dissolution data have been analyzed according to the main kinetic models and their Excipient Efficiencies for prolonged release have been calculated. The principal parameters of the SeDeM Expert system, such as the parametric profile (mean radius) and the good compression index obtained for the polymers are above the values considered as adequate for direct compression even without addition of flow agents. The obtained values for Excipient Efficiency show good ability of the polymer to control the drug release. Finally, in the case of PU(dithiodiethanol-DTDI), a clear increase in the release rate has been observed when the formulation is subjected to colon simulating conditions.