Innovative Drug Delivery Research, Piramal Healthcare Research Centre, Mumbai-400063 India.
Curr Drug Deliv. 2009 Oct;6(5):477-85. doi: 10.2174/156720109789941641.
Metformin Hydrochloride (MF) is glucose lowering agent that is widely used for management for type II diabetes. MF is reported to be absorbed mainly in upper part of GIT. It is having narrow absorption window and high water solubility, and it would be more beneficial to retain the drug in stomach for prolonged duration so as to achieve maximum absorption and better bioavailability. A conventional oral CR formulation releases most of the drug content at the colon, which requires that the drug will be absorbed from the colon. The present investigation is aimed to develop novel gastroretentive (GR) drug delivery system, which not only release the drug in the absorption window but also provides controlled release drug profile that may result patient compliance and therapeutic success. Floating tablets of MF was prepared using sodium alginate, and sodium carboxymethylcellulose was used as a gelling agent, and release modifiers, respectively. Eudragit NE 30 D was used as sustained release polymer to control the initial burst release. Drug and excipients compatibility studies were monitored by thermal analysis by using differential scanning calorimeter. 32 full factorial design was applied to optimize the formulation. The DSC thermogram of drug, polymer and physical mixtures revealed that there was no known interaction between drug and polymers. The prepared tablets were evaluated for in vitro dissolution, in vitro buoyancy, percentage swelling, percentage erosion and similarity factors with marketed tablets. The optimization study using a 32 full factorial design revealed that the amount of sodium alginate and sodium carboxymethylcellulose had a significant effect on t50, t90, Flag and f2. Thus, by selecting a suitable composition of release rate modifier and gel forming agent, Gastro retentive system can be developed with the desired dissolution profile. This study indicated that the MF GR tablets prepared using sodium alginate and sodium carboxymethylcellulose can successfully be employed as a once-a-day oral controlled release drug delivery system.
盐酸二甲双胍（MF）是一种广泛用于 II 型糖尿病治疗的降血糖药物。据报道，MF 主要在上消化道被吸收。它的吸收窗口较窄，水溶性较高，因此将药物在胃中保留更长时间以实现最大吸收和更好的生物利用度更为有利。传统的口服控释（CR）制剂在结肠中释放大部分药物，这需要药物从结肠吸收。本研究旨在开发新型胃滞留（GR）药物递送系统，该系统不仅可以在吸收窗内释放药物，还可以提供控制释放药物的特征，从而提高患者的顺应性和治疗成功率。MF 的漂浮片是用海藻酸钠和羧甲基纤维素钠制备的，分别用作凝胶剂和释放调节剂。Eudragit NE 30 D 用作控制初始突释的缓释聚合物。通过使用差示扫描量热法（DSC）进行热分析来监测药物和赋形剂的相容性研究。应用 32 全因子设计优化配方。药物、聚合物和物理混合物的 DSC 热图谱表明药物与聚合物之间没有已知的相互作用。对制备的片剂进行体外溶出度、体外漂浮性、溶胀率、侵蚀率和与市售片剂的相似因子进行评价。32 全因子设计的优化研究表明，海藻酸钠和羧甲基纤维素钠的用量对 t50、t90、Flag 和 f2 有显著影响。因此，通过选择合适的释放速率调节剂和凝胶形成剂的组成，可以开发出具有所需溶解特性的胃滞留系统。这项研究表明，使用海藻酸钠和羧甲基纤维素钠制备的 MF GR 片剂可以成功地用作一日一次的口服控释药物递送系统。
