The release behavior of the combined system of diltiazem hydrochloride delayed-onset sustained-release pellets and modeling by mathematics method / 药学学报

ABSTRACT

<p><b>AIM</b>To prepare the combined system of diltiazem hydrochloride delayed-onset sustained-release pellets in order to make time-specific drug delivery system. The drug can release from the system sustained after a predetermined lag time, and the release behavior can continue till 24 hour after administrating the formulation. According to the concept of chronotherapy, the combined system is useful to improve the pharmacotherapy of cardiovascular diseases.</p><p><b>METHODS</b>The velocity-time curve of the drug release from the multiple-unit system containing pellets was consistent with the fluctuation curve following time of blood pressure and heart ratio. So the velocity-time curve was selected to describe the release behavior of the combined system. The velocity-time equation describing the release behavior of two kinds of pellets was deduced by non-linear least square model fit. And zero-order kinetics equation was adopted to fit the release behavior of different combinations which were composed of different proportion of two kinds of pellets. The velocity-time equation describing the release behavior of the combinations was deduced by non-linear least square model fit, too. The difference of combinations in velocity-time curves between theoretical value and test value was compared.</p><p><b>RESULTS</b>The results showed that the test values were closely approximate to the theoretical values. Therefore, the multiple unit drug delivery system can be described by adding the velocity-time equations of different pellets to calculate the theoretical equations.</p><p><b>CONCLUSION</b>A multiple-unit combined system containing different coated pellets, as a novel delayed-onset sustained-release system, was prepared. Then a time-specific drug delivery system has been made. The programmed drug delivery system could be predicted by adding the velocity-time equation of each kind of pellets to calculate the theoretical equations. characterized by mathematics equation. The release behavior of pellets system could be characterized by mathematics equation.</p>