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

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 C_max (maximum concentration), T_max, 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 C_max and T_max, 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.

Keywords::

• Urapidil
• modified-release pellets
• centrifugal granulation
• fluidized bed coater
• bioavailability

Acknowledgments

Dr David B. Jack and Yue Cui are gratefully thanked for correcting the manuscript.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.