格列美脲凝胶骨架控释贴剂的制备及体内外评价  

Preparation and evaluation in vivo and in vitro of glimepiride gel-matrix controlled-release patch

作　　者：张援[1] 许东晖[1] 马争[2] 陈颖 赵君军 许实波[1] 

机构地区：[1]中山大学药学院,广东广州510275 [2]山西医科大学公共卫生学院,山西太原030001 [3]广东省体育科学研究所省重点实验室,广东广州510100

出　　处：《药学学报》2004年第8期640-644,共5页Acta Pharmaceutica Sinica

摘　　要：目的　研究格列美脲凝胶骨架控释贴剂的药剂学性质及其经大鼠皮肤给药的药代动力学和相对于口服水溶液的生物利用度。方法　建立格列美脲体外含量测定的HPLC方法 ,考察贴剂的体外透皮吸收速率和经皮渗透机制 ,并进行质量控制和评价 ;建立高灵敏度的HPLC柱前衍生化方法测定格列美脲血药浓度 ,研究贴剂经皮给药后在大鼠体内的药代动力学和生物利用度。结果　该控释贴剂具零级动力学特征 ,其含量测定和重量差异检查符合2 0 0 0年版中国药典规定 ,稳定性好 ;贴片给药的血药浓度明显较口服平稳 ,达峰时间推后 ,持效时间延长 ,相对生物利用度为 2 0 3%。结论　格列美脲凝胶骨架型贴剂经皮给药后 ,能使药物的吸收和消除较口服缓慢而持久 。Aim To study the pharmaceutical characterization, the pharmacokinetics and relative bioavailability of glimepiride gel-matrix controlled-release patch in rats. Methods An HPLC method was established for the determination of glimepiride in the permeation receptor and patch. The permeation rate and penetration mechanism of glimepiride-TDDS through rabbit skin in vitro was examined. The determination of drug content and the examination of weight difference and stability of the glimepiride-TDDS were carried out. Another HPLC method after pre-column derivatization was developed to determine the glimepiride serum concentration and then employed to study the pharmacokinetics and relative bioavailability of glimepiride after a single dose of oral or patch administration in rats. Results The permeation tests through excised rabbit skin demonstrated that the optimized glimepiride controlled-release patch exhibited zero-order kinetic characteristics that satisfied the demands of original design. The determination of glimepiride content and the quality control of weight difference of the patch accorded with Pharmacopoeia of the People′s Republic of China of 2000 edition and the pharmaceutical characterization showed good stability. The HPLC method for the determination of serum glimepiride was shown to be a sensitive and simple one. The pharmacokinetic results showed that TDDS could decrease the maximum serum concentration, prolong the peak time, extend the MRT by 5.5 times compared with oral administration and maintain the serum concentration of glimepiride at a higher level even after 120 h of administration. The relative bioavailability of glimepiride-TDDS was 20.3% versus oral administration. Conclusion The glimepiride-TDDS showed a slower, longer and smoother serum concentration-time profile, as compared with conventional oral administration in both absorption and elimination phase. As a result, it was evident that the patch exhibited good controlled-release properties.

关 键 词：格列美脲 凝胶骨架控释贴剂 制备 药剂学 药代动力学 生物利用度 

分 类 号：R94[医药卫生—药剂学]