格列美脲凝胶骨架控释贴剂的制备及体内外评价

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2000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20.3%。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，具明显的控释特征。

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

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.