Wang Xun, Nie Shu-fang, Li Wei, Luan Lin, Pan Weisan
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, PR China.
Drug Dev Ind Pharm. 2007 Sep;33(9):1024-9. doi: 10.1080/03639040601179897.
Controlled release bi-layer osmotic pump tablets (BOPT) of water-insoluble allopurinol with large dose (150 mg/BOPT) were successfully prepared merely with sodium chloride as osmotic promoting agent and polyethylene oxide (PEO) as suspending agent. Formulations of the two kinds of agents were investigated in order to discuss their effects on the release behavior of BOPT, and then the optimal formulation was evaluated. The pharmacokinetics studies of allopurinol and its active metabolite oxypurinol in two-preparation and two-period crossover design relative to the equivalent dose of commercially common allopurinol tablets were evaluated in six Beagle dogs. And the pharmacokinetics results showed that allopurinol BOPT were able to provide a slow release of allopurinol, and oxypurinol were bioequivalent between allopurinol BOPT and common allopurinol tablets. A good in vitro-in vivo correlation of allopurinol was also proved. In conclusion, water-insoluble drugs with large dose can be designed to BOPT for efficacy and safety use.
仅以氯化钠作为渗透促进剂、聚环氧乙烷（PEO）作为悬浮剂，成功制备了大剂量（150毫克/双层渗透泵片）的水不溶性别嘌醇控释双层渗透泵片（BOPT）。研究了这两种制剂的配方，以探讨它们对BOPT释放行为的影响，进而评估最佳配方。在6只比格犬中，采用双制剂、双周期交叉设计，相对于等效剂量的市售普通别嘌醇片，对比研究了别嘌醇及其活性代谢产物氧嘌呤醇的药代动力学。药代动力学结果表明，别嘌醇BOPT能够实现别嘌醇的缓释，且别嘌醇BOPT与普通别嘌醇片之间的氧嘌呤醇具有生物等效性。同时也证明了别嘌醇具有良好的体内外相关性。综上所述，大剂量水不溶性药物可设计制成BOPT，以实现有效且安全的使用。
