Yong C S, Jung J H, Rhee J D, Kim C K, Choi H G
College of Pharmacy, Yeungnam University, Dae-Dong, Gyongsan, South Korea.
Drug Dev Ind Pharm. 2001 May;27(5):447-55. doi: 10.1081/ddc-100104320.
The objective of this study was to develop an effective omeprazole buccal adhesive tablet with excellent bioadhesive force and good drug stability in human saliva. The omeprazole buccal adhesive tablets were prepared with various bioadhesive polymers, alkali materials, and croscarmellose sodium. Their physicochemical properties, such as bioadhesive force and drug stability in human saliva, were investigated. The release and bioavailability of omeprazole delivered by the buccal adhesive tablets were studied. As bioadhesive additives for the omeprazole tablet, a mixture of sodium alginate and hydroxypropylmethylcellulose (HPMC) was selected. The omeprazole tablets prepared with bioadhesive polymers alone had bioadhesive forces suitable for a buccal adhesive tablet, but the stability of omeprazole in human saliva was not satisfactory. Among alkali materials, only magnesium oxide could be an alkali stabilizerfor omeprazole buccal adhesive tablets due to its strong waterproofing effect. Croscarmellose sodium enhanced the release of omeprazole from the tablets; however, it decreased the bioadhesive forces and stability of omeprazole tablets in human saliva. The tablet composed of omeprazole/sodium alginate/HPMC/magnesium oxide/croscarmellose sodium (20/24/6/50/10 mg) could be attached on the human cheek without disintegration, and it enhanced the stability of omeprazole in human saliva for at least 4 h and gave fast release of omeprazole. The plasma concentration of omeprazole in hamsters increased to a maximum of 370 ng/ml at 45 min after buccal administration and continuously maintained a high level of 146-366 ng/ml until 6 h. The buccal bioavailability of omeprazole in hamsters was 13.7% +/- 3.2%. These results demonstrate that the omeprazole buccal adhesive tablet would be useful for delivery of an omeprazole that degrades very rapidly in acidic aqueous medium and undergoes hepatic first-pass metabolism after oral administration.
本研究的目的是开发一种有效的奥美拉唑口腔黏附片，使其具有优异的生物黏附力，并在人唾液中具有良好的药物稳定性。采用多种生物黏附聚合物、碱性材料和交联羧甲基纤维素钠制备奥美拉唑口腔黏附片。研究了它们的理化性质，如生物黏附力和在人唾液中的药物稳定性。研究了口腔黏附片递送的奥美拉唑的释放和生物利用度。作为奥美拉唑片的生物黏附添加剂，选择了海藻酸钠和羟丙基甲基纤维素（HPMC）的混合物。单独用生物黏附聚合物制备的奥美拉唑片具有适合口腔黏附片的生物黏附力，但奥美拉唑在人唾液中的稳定性并不理想。在碱性材料中，只有氧化镁因其强大的防水作用可作为奥美拉唑口腔黏附片的碱性稳定剂。交联羧甲基纤维素钠可增强奥美拉唑从片剂中的释放；然而，它降低了奥美拉唑片在人唾液中的生物黏附力和稳定性。由奥美拉唑/海藻酸钠/HPMC/氧化镁/交联羧甲基纤维素钠（20/24/6/50/10mg）组成的片剂可附着在人脸颊上而不崩解，并且它在人唾液中增强了奥美拉唑的稳定性至少4小时，并使奥美拉唑快速释放。仓鼠经口腔给药后45分钟，奥美拉唑的血浆浓度最高升至370ng/ml，并持续维持在146 - 366ng/ml的高水平直至6小时。奥美拉唑在仓鼠中的口腔生物利用度为13.7%±3.2%。这些结果表明，奥美拉唑口腔黏附片对于递送在酸性水性介质中迅速降解且口服后经历肝脏首过代谢的奥美拉唑将是有用的。
