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Study On Properties And Release Behavior Of Konjac Glucomannan/xanthan Gum Plural Gel For Drug Carrier

Posted on:2011-09-10Degree:MasterType:Thesis
Country:ChinaCandidate:Z H WeiFull Text:PDF
GTID:2121360308464257Subject:Polymer Chemistry and Physics
Abstract/Summary:PDF Full Text Request
Konjac glucomannan (KGM) and xanthan gum (XG) are both natural polysaccharides from aboundant renewable resources. They have been used as food or food additives in food industry. KGM and XG are well-known for their excellent biocompatibility and biodegradability. Their degraded products are non-toxic and innocuous to human and environment. It has been found that there exists a strong synergism between KGM and XG so that the KGM/XG plural gel possesses higher viscosity and intensity than the corresponding individual KGM gel or XG gel with the same concentration; and the studies have been proved and KGM cannot be degraded in the upper gastrointestinal (UGIT), but it can be degraded via the action ofβ-mannanases produced by colonic flora. And XG cannot be degraded by human digestive enzyme. These properties endow the KGM/XG plural gel with the basic features as a carrier for slow-release fertilizer and oral drugs. Therefore, it is of great significance to design and prepare KGM/XG plural gels with appropriate intensity and swelling behavior and to investigate their release behavior as as a carrier for slow-release fertilizer and oral drugs.In this work, a series of KGM/XG plural gels were prepared under 0.2~2.0 wt % of total polysaccharides concentration and different KGM/XG mass ratio. Texture Profile Analysis (TPA) and rheological tests (RDA) were used to study the strength of KGM/XG plural gels. The results showed that the KGM/XG plural gel prepared under the conditions of 1.0 wt % of total polysaccharides concentration and KGM/XG mass ratio 1∶1 exhibited a strong synergism, leading to high intensity; and its three-dimentional network maintained relative stableness under certain pressure and temperature. The studies on the their swelling behaviors in different aqueous media indicated that the KGM/XG plural gels are sensitive to pH of the media. The swelling of the plural gel was restrained under acidic condition of pH?6.0; on the other hand, the swelling ratio increased with a raising pH in alkali aqueous media of pH 6.0~8.0, and reached its maximum at pH 8.0.Based on the above results, the drug-loading KGM/XG plural gels were prepared using one of the most important nitrogenous fertilizers, urea, an anti-Parkinson's disease drug Laevodopa (L-Dopa) and an anti-colitis drug 4-aminosalicylic acid (4-ASA) as model drugs, respectively. Their properties, release behavior and mechanism were investigated under different pH and temperatures. The results are as follows:(a) The urea/KGM/XG plural gels possess the similar properties to KGM/XG plural gel. The KGM/XG plural gels embedding L-Dopa or 4-ASA exibit high intensity and low swelling ratio due to the hydrogen bonds interaction between L-Dopa or 4-ASA and polysaccharides. This phenomenon is particularly obvious when the drug loading amounts are 25.0 mg/g. This effect is propitious to suppress the drug release from the plural gel, thus realizating slow-release and control-release.(b) The urea release from the urea/KGM/XG plural gels is controlled by its swelling behavior in neutral water. Raising temperature will accelerate the collapse of the plural gel, so as to accelerate and increase the mass release ratio. The release behavior of the urea/KGM/XG plural gel strongly depends on the pH values of the media. The pH of aqueous medium had a great influence on the release behavior of urea from the plural gel. In alkaline medium, the release of urea will be accelerated and the accumulative release amount of urea will increase remarkably. On the contrary, the acidic medium will make the release of urea repressed, so that the slow release of urea from the plural gel within a relatively long time can be realized.(c) The drugs release behaviors from the L-Dopa/KGM/XG plural gels and 4-ASA/KGM/XG plural gels in vitro were highly pH sensitive. The accumulative release amount of L-Dopa and of 4-ASA reached 13.21 % and 7.38% respectively in the first 3 h under pH 1.0 aqueous medias simulating the gastric juice; the accumulative release amount reached 53.53 % and 76.62 % for L-Dopa and 63.00 % and 68.04 % for 4-ASA under pH 6.8 and pH 7.4 buffer solutions. Thus, the KGM/XG plural gels embedding L-Dopa or 4-ASA can reduce first pass effect; decrease the times for oral drugs and the toxic side-effects of L-Dopa and 4-ASA, slow-release targeting of drugs in coloncan be realized.(d) Rigter-Peppas model was adopted to analyse the release data of L-Dopa/KGM/XG plural gels and 4-ASA/KGM/XG plural gels to elucidate the drugs release mechanism. The models indicated similar fitting to the L-Dopa experimental data and release parameter n ? 0.45, thus, the release of L-Dopa followed Fickian diffusion mechanism. The n value of 4-ASA from the plural gels at pH 1.0 and pH 6.8 were 0.3307 and 0.3959, both beneath 0.45, which indicated Fickian diffusion was also the mechanism of 4-ASA release from the plural gels. However, at pH 7.4, the n value of 4-ASA was 0.5848, representing the drug release from the KGM/XG plural gels followed the anomalous transportation mechanism, which is both the Fick diffusion and polymer chain relaxation contribute to the drugs release.
Keywords/Search Tags:Konjac glucomannan (KGM), xanthan gum (XG), plural gel, urea, laevodopa (L-Dopa), 4-aminosalicylic acid (4-ASA), slow-release
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