College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, PR China.
Pharm Dev Technol. 2011 Jun;16(3):212-8. doi: 10.3109/10837451003592191. Epub 2010 Feb 15.
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.
研制含有乌拉地尔的控释微丸，并考察其体内生物利用度。
以乳糖和 MCC 为主要填充剂，采用离心造粒的粉末包衣法，用流化床包衣机包衣，制备载药层微丸。用甲基丙烯酸共聚物水分散体制备具有不同释药特性的微丸。
选用商品化的德国胶囊（R）作为参比制剂，经优化后选择两种包衣处方进行考察：Eudragit（R）NE30D/L30D55 比例为 10∶1，包衣增重 3%的 pH 依赖性微丸（T（1））和 Eudragit（R）NE30D 包衣增重 3.5%的 pH 不依赖性微丸（T（2））。以单剂量、三周期、一周洗脱期的交叉设计，在 6 名健康受试者中进行口服给药后微丸（T（1）、T（2）中分别含 30mg 乌拉地尔）的生物利用度试验。用 HPLC-UV 法测定乌拉地尔的血药浓度。T（1）的 C（max）（峰浓度）、T（max）和 MRT 分别为 311.7ng/ml、5.3h 和 8.3h。T（1）与 R 生物等效，相对生物利用度为 110.9%。T（2）的 C（max）和 T（max）分别为 105.3ng/ml 和 13.3h，相对生物利用度为 72.7%。
pH 依赖性乌拉地尔微丸具有较高的生物利用度。
