LAG TIME METHOD TO DELAY DRUG-RELEASE TO VARIOUS SITES IN THE GASTROINTESTINAL-TRACT

The lag times delayed by the hydration of various thicknesses of films were studied in an attempt to deliver drugs to various sites in the g astrointestinal (GI) tract. In a theoretical simulation, it was found that the lag time could be controlled by varying the thickness of the coated polymer, which was equivalent to the amount of polymer coated a ssuming that the density of the dry polymer was constant. A higher rat io of drug solubility relative to the dosing amount promoted rapid rel ease of drug after the lag period. Diltiazem hydrochloride was selecte d as a model drug with high and pH-independent water solubility. In vi tro dissolution in the pH change medium demonstrated that the release pattern of diltiazem hydrochloride from pellets coated with various th icknesses of Eudragit RS film was kept unchanged. Drug release exhibit ed a lag period followed afterwards by instantaneous release. The rela tionship between the lag time and the square of the amount of polymer coated, as well as that between the release rate at steady state and t he inverse of the amount of polymer coated, appeared to be linear as p redicted.