Preparation of pH-dependent modified-release pellets of urapidil to improve its bioavailability

Modified-release pellets containing urapidil were developed and its in vivo bioavailability was investigated.

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.

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 (T(1)), and pH-independent pellets with a Eudragit(®) NE30D coating level (T(2)) of 3.5%. The bioavailability of the pellets (T(1), T(2), 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 C(max) (maximum concentration), T(max), and MRT of T(1) were 311.7 ng/mL, 5.3 h and 8.3 h, respectively. T(1) was bioequivalent to R, with a relative bioavailability 110.9%. The C(max) and T(max), of T(2) were 105.3 ng/mL and 13.3 h, respectively, and the relative bioavailability was 72.7%.

The pH-dependent urapidil pellets have a high bioavailability.