DESIGN AND CHARACTERIZATION OF CHRONOPHARMACEUTICAL DRUG DELIVERY OF PROPRANOLOL HYDROCHLORIDE

Objectives: In the present study, an effort was made to develop a novel pulsatile dosage form for the treatment of hypertension using Propranolol hydrochloride as a model drug. A time-delayed capsule was prepared by sealing the pellets inside the insoluble hard gelatin capsule body with an erodible hydrogel plug. Methods: The pellets were prepared by the Fluidized Bed Wurster (bottom spray) technique. 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 4.5 kg/cm² hardness and 100 mg weight was placed in the capsule opening and found suitable to avoid the drug release in small intestinal fluid and eject the plugin colonic fluid, releasing the pellets into colonic fluid after a lag time criterion of 5 h. Three dissolution media with pH 1.2, 7.4 and 6.8 were consecutively used to simulate the pH changes along the GI tract. Results: FTIR study confirmed that there was no interaction between drug and polymer. Among all the formulations Propranolol hydrochloride pellets coated with Eudragit FS 30D in 35% w/w concentrations shown prolonged release for a period of 12 h. Conclusion: The obtained results revealed capability of system in controlling drug release for a programmable period of time and prevent a sharp increase in the incidence of blood pressure, during the early morning h, a time when the risk of hypertension attacks is maximum.