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

• Published in: Pharmaceutical development and technology Vol. 16; no. 3; pp. 212 - 218
• Main Authors: He, Haibing, Li, Hui, Tang, Xing
• Format: Journal Article
• Language: English
• Published: England Informa Healthcare 01.06.2011; Taylor & Francis
• Subjects: Administration, Oral; bioavailability; Biological Availability; centrifugal granulation; Cross-Over Studies; Excipients - chemistry; fluidized bed coater; Humans; Hydrogen-Ion Concentration; Hypromellose Derivatives; Intestines - metabolism; Male; Methacrylates - chemistry; Methylcellulose - analogs & derivatives; modified-release pellets; Piperazines - administration & dosage; Piperazines - blood; Piperazines - pharmacokinetics; Polyethylene Glycols - chemistry; Polymers - chemistry; Randomized Controlled Trials as Topic; Solubility; Tablets, Enteric-Coated - chemistry; Tablets, Enteric-Coated - pharmacokinetics; Talc - chemistry; Urapidil; Young Adult
• ISSN: 1083-7450; 1097-9867; 1097-9867
• DOI: 10.3109/10837451003592191

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.