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


CONCLUSIONS
The pH-dependent urapidil pellets have a high bioavailability.
He
Haibing
H
College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, PR China.
Li
Hui
H
Tang
Xing
X
D000284:Administration, Oral; D001682:Biological Availability; D018592:Cross-Over Studies; D005079:Excipients / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D065347:Hypromellose Derivatives; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008689:Methacrylates / Q000737:chemistry; D008747:Methylcellulose / Q000031:analogs & derivatives; D010879:Piperazines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D016032:Randomized Controlled Trials as Topic; D012995:Solubility; D013608:Tablets, Enteric-Coated / Q000737:chemistry / Q000493:pharmacokinetics*; D013627:Talc / Q000737:chemistry; D055815:Young Adult
C477852:Eudragit L 30 D-55; C477853:Eudragit NE 30-D; D005079:Excipients; D008689:Methacrylates; D010879:Piperazines; D011108:Polymers; D013608:Tablets, Enteric-Coated; D013627:Talc; D065347:Hypromellose Derivatives; D011092:Polyethylene Glycols; D008747:Methylcellulose; C015568:urapidil