Abstract: | Objective: Modified-release pellets containing urapidil were developed and its in vivo bioavailability was investigated.Methods: Lactose and MCC were used as the main fillers to prepare drug-layer pellets by the powder layering method using centrifugal granulation, and coated in a fluidized bed coater. Pellets with different drug release characteristics were prepared with a methacrylic acid copolymer aqueous dispersion.Results: Using commercial German capsules as the reference (R), two coating formulations were selected for tests after optimization: pH-dependent pellets with a ratio of Eudragit® NE30D/L30D55 of 10:1, a 3% coating level (T1), and pH-independent pellets with a Eudragit® NE30D coating level (T2) of 3.5%. The bioavailability of the pellets (T1, T2, containing 30?mg urapidil) was determined in six healthy subjects after oral administration of a single dose, for a period of three weeks, in the form of a crossover design with a wash-out period of one week. The plasma concentrations of urapidil were determined by HPLC with UV detection. The Cmax (maximum concentration), Tmax, and MRT of T1 were 311.7?ng/mL, 5.3?h and 8.3?h, respectively. T1 was bioequivalent to R, with a relative bioavailability 110.9%. The Cmax and Tmax, of T2 were 105.3?ng/mL and 13.3?h, respectively, and the relative bioavailability was 72.7%.Conclusion: The pH-dependent urapidil pellets have a high bioavailability. |