ABSTRACT:
In the present study, an effort was made to develop a novel dosage form by using a chrono-pharmaceutical approach for the treatment of hypertension using Diltiazem hydrochloride as a model drug. A time delayed capsule was prepared by sealing the pellets inside the insoluble hard gelatin capsule body with erodible hydrogel plug. The pellets were prepared by emulsion Fluidized Bed Wurster (bottom spray) technology technique. Optimized pellets formulations were selected based on dissolution studies. The entire device was enteric coated, so that the variability in gastric emptying time can be overcome and a colon-specific release can be achieved. Hydrogel plug (HPMCK4 and lactose in 1:1 ratio) having 4.5kg/cm2 hardness and 100 mg weight was placed in the capsule opening and found that it was suitable to avoid the drug release in small intestinal fluid and to eject out the plug in colonic fluid and releasing the pellets into colonic fluid after a lag time criterion of 5 hours. In order to simulate the pH changes along the GI tract, three dissolution media with pH 1.2, 7.4 and 6.8 were successively used. FTIR study confirmed that there was no interaction between drug and polymer. Among all the formulations Diltiazem hydrochloride pellets coated with Eudragit FS 30D in 35% w/w concentrations shown prolonged release for a period of 12 hours. The obtained results revealed the capability of the system in delaying drug release for a programmable period of time and can prevent a sharp increase in the incidence of blood pressure, during the early morning hours, a time when the risk of hypertension attacks is the maximum.