Development and Characterization of Expandable Gastroretentive Delivery System (GRDS)

• Main Authors: SIOW WEN SHIAN, 蕭雯萱
• Other Authors: SHEU, MING-THAU
• Format: Others
• Language: en_US
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/61003630443806756439

碩士 === 臺北醫學大學 === 藥學系 === 94 === The aim of the study was to develop a novel expandable gastroretentive drug delivery system. We have been interested in developing the devices based on swellable polymers combining with several functionalities in the unit. In our studies, the investigation of different formulation factors included the following five categories, i.e. different combination of swellable polymers, the addition of chargable polymers, different combination of ionic complexes of polymers, the addition of osmogents and the addition of wicking agents on the swelling behavior was conducted. Physical characterizations of the tablets including swelling index based on weight variation and visual swelling observations were carried out to have comprehensive understanding of the swelling properties for different combination of polymers and excipients with different functionalities. Results demonstrate that the swelling ability of higher molecular weight PEO (M.W.8,000,000) was greater than HEC 250HHX alone. However, when NaCMC 450 cps were added in the same ratio to both swellable polymer, it was interesting to found that the swelling size of the combination with HEC 250HHX were much larger than the combination with PEO M.W.8,000,000. On the other hand, the addition of polyionic complexes showed only slightly improvement in swelling index. However, the addition of both osmogents and wicking agents did not show significant improvement in swelling index compared to HEC 250HHX alone. Among the five categories, we found that the combination of HEC 250HHX and NaCMC 450 cps in the ratio of 60:40 exhibited the greatest swelling index. Subsequently, three different solubility drugs were incorporated in the expandable formulations (HEC 250HHX:NaCMC 450 cps = 60:40) to investigate the influences of the drug solubility on the drug release pattern and swelling behaviors in the medium containing various NaCl concentration (A: 0, B: 0.1, C: 0.5, D: 0.9%). Results reveal that the rank order of decreasing release rate for freely water soluble drug Metformin was D>C>A>B, in which the solubility of Metformin in 0.1% NaCl was exactly much lower than the others. The rank order of decreasing release rate was D>C>B>A for water soluble drug Ciprofloxacin. Due to its highly soluble in various NaCl concentration, this might be caused by the extent of the hindrance in the formation of gel layer increased with increasing NaCl concentration leading to the faster release rate. However, the rank order of decreasing release rate was A>C>D>B for slightly soluble drug Esomeprazole, in which the difference of release rate was not significant pronounced that the influence of NaCl concentration on the release profile of Esomeprazole could be neglected. Furthermore, it was elucidated that the release mechanism of Metformin was mainly by diffusion controlled release, while the release mechanism of Ciprofloxacin and Esomeprazole were mainly by anomalous diffusion release. In conclusion, the developed gastroretentive device composed of HEC and NaCMC possessed significantly excellent swelling potential for longer gastric retention with sustained drug release characteristics.