• Journal of Pharmaceutical Investigation
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• 제35권5호
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• pp.369-373
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• 2005

The objectives of the current work is to understand the factors impacting the formulation and performance of a Carbopol mucoadhesive buccal delvery system for a model peptide drug, $[D-Ala{^2},\;D-Leu{^5}]$enkephalin (DADLE, Mw=569.7) with comparable chemical and enzymatic stability. Specifically, in vitro buccal DADLE delivery from the cross-linked poly(acrylic acid) (PAA) hydrogel system was characterized. In addition, the influences of several penetration enhancers on the ex vivo buccal absorption of DADLE were also studied. In this study, the PAA hydrogels generally swell to 100% of their original weight in the phosphate pH 7.4 buffer. The water penetration into the PAA hydrogel occurred based on a zero-order kinetics for the first 60 min and steadily decreased afterwards. From the release study, it can be seen that the initial DADLE release was so rapid and the rate of release of DADLE decreased as the time elapsed. The porcine buccal tissue was found to be permeable to DADLE with a flux value of $0.07%/cm{^2}/hr({\pm}0.01\;SD)$. From the ex vivo diffusion study, it was found that sodium taurodihydrofusidate showed a greater degree of enhancement compared to the phospholipids with an Enhancement Ratio (ER) of 8.7 compared to 2.7 and 1.9 for didecanoylphosphatidylcholine and lysophosphatidylcholine, respectively. The work encompassed within this paper has demonstrated the feasibility of using the PAA hydrogel delivery system with its good mucoadhesive properties for the buccal delivery of peptides.

• Journal of Pharmaceutical Investigation
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• 제26권2호
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• pp.137-144
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• 1996

The study was carried out for the preparation and evaluation of a buoyant hydrogel matrix (BHM), which is buoyant in a neutral or in pH 2.0 buffer solution, by the aspects of buoyancy, swelling, and drug release. Physical mixtures of HPC and CP in various molar ratio were employed as a mucoadhesive polymer which swells and controls the rate of drug release. Anhydrous citric acid and sodium bicarbonate in the molar ratio of 1:3 were employed as effervescing agents which provide a buoyancy for the mucoadhesive polymeric matrix. The buoyancy in vitro was expressed as both floating time$(T_{fl})$ and surfing time$(T_{sf})$, which are the time required for floating from the bottom to the surface of the medium and the time to keep the floated state at the surface of medium during release studies, respectively. A close relationship was observed between the buoyancy and the amount of effervescing agent added. $T_{fl}$ of the buoyant hydrogel matrices were decreased to about 10 seconds linearly with increasing the amount of effervescing agent in the range of 5 to 15%. $T_{sf}$ of the buoyant hydrogel matrices were varied from 1 to 3 hr depending on the amount of effervescing agent. The swelling was observed by changes in diameter of the buoyant hydrogel matrices in distilled water or acidic buffer solution, resulted in dependences on pH and the amount of effervescing agents. The release of hydrochlorothiazide from the buoyant hydrogel matrices were followed by apparent zero-order kinetics, while the buoyant hydrogel matrices were floated at the surface and maintaining their swollen shapes.

• Journal of Pharmaceutical Investigation
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• 제36권2호
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• pp.83-87
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• 2006

Poly(acrylic acid) (PAA) was identified to possess good mucoadhesive properties ensuring its application to extend the retention times of the formulations at the oral cavity, intended route of administration using the polymer. In the noncross-linked state, PAA will swell and become eroded owing to the presence of salivary flow from the site of application. The formation of cross-links between the polymer chains will allow swelling but prevents the erosion of the dosage form. In the current study, cross-linking was achieved by esterification of the PAA chains with sucrose. The density of crosslinking was modified by changing sucrose concentration and the duration of cure time. The cross-linking density of the polymer hydrogel was assessed by equilibrium swelling studies. The mucoadhesion testing method allowed a comparative study of the hydrogels prepared. An inverse relationship between equilibrium swelling and peak detachment force showed that increased PAA chain density per unit area enhanced the mucoadhesive interaction.

• Archives of Pharmacal Research
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• 제26권8호
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• pp.659-665
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• 2003

We have studied the effect of rhEGF on the buccal mucosal ulcer healing. rhEGF was rapidly degraded upon incubation with the hamster buccal mucosal homogenates; The degradation of rhEGF was significantly inhibited by sodium lauryl sulfate (SLS). Eudispert hv hydrogel and Polycarbophil 974P hydrogel were prepared for rhEGF delivery and their mucoadhesiveness was measured by the $Instron^R$ method. The mucoadhesive force of Eudispert hv was significantly greater than that of Polycarbophil 974P. Moreover, rhEGF in Eudispert hv hydrogel remained stable for about 2 months. To evaluate the ulcer healing effect of rhEGF, the buccal mucosal ulcer was induced in golden hamsters using acetic acid. At 24 h after administration of rhEGF/Eudispert hv hydrogel, the ulcerous area was decreased compared with rhEGF solution and, as a result, the curative ratio was $36.8\pm5.68$%. By the addition of SLS (0.5%) to Eudispert hv hydrogel, the curative ratio increased 1.5 times. The mechanism of the action was probably due to a combination of protection of the drug against proteases present in mucosa and prolongation of the release of rhEGF from the formulation at the site of action.

• 폴리머
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• 제36권2호
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• pp.182-189
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• 2012

본 연구에서는 전자빔을 이용하여 폴록사머 하이드로젤을 제조하여 구강 점막부착성 약물전달체로서의 특성을 평가하고자 하였다. 온도감응성을 나타내는 폴록사머 고분자의 말단에 가교반응을 위한 비닐기를 도입한 후, 방사선 가교반응을 이용하여 하이드로젤을 제조하였다. 점착성 향상을 위한 첨가제로 점착성 고분자인 카보폴을 첨가하여 하이드로젤을 제조하였고, 카보폴이 점막부착성과 서방성 방출에 미치는 영향을 알아보았다. 결과적으로, 폴록사머 고분자의 말단 개질과 카보폴의 첨가에 의해 하이드로젤의 기계적 물성과 점막부착성이 향상되었고, 약물방출실험 결과 약물이 방출되는 속도가 지연되는 결과를 확인하였다.

• Bulletin of the Korean Chemical Society
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• 제35권8호
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• pp.2391-2399
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• 2014

Novel dual responsive pectin hydrogels composed from poly(acrylamidoglycolic acid-co-vinylcaprolactam)/Pectin (PAV-PC) and also PAV-PC hydrogels are used as templates for the production of silver nanoparticles. 5-Fluorouracil is an anticancer drug and has been loaded in situ into PAV-PC hydrogels. Structure and morphology characterization of PAV-PC hydrogels were investigated by fourier transform infrared spectroscopy, differential scanning calorimetry, thermo gravimetric analysis, X-ray diffraction studies, scanning electron microscopy and transmission electron microscopy. The results revealed a molecular level dispersion of the drug in PAV-PC hydrogels. In vitro release of 5-fluorouracil from the PAV-PC hydrogels has been carried out in GIT fluids as well as in various temperatures. 5-Fluorouracil released from PAV-PC hydrogels was 50% at pH 1.2, and 85% at pH 7.4 within 24 h. The release profile was characterized with PAV-PC hydrogels and initial burst effect was significantly reduced in two buffer media (1.2 and 7.4), followed by a continuous and controlled release phase, the drug release mechanism from polymer was due to Fickian diffusion. In situ fabrication of silver nanoparticles inside the hydrogel network via the reduction of sodium borohydrate by PAV-PC chains led to hydrogel nanocomposites. The diameter of the nanocomposites was about 50-100 nm, suitable for uptake within the gastrointestinal tract due to their nanosize range and mucoadhesive properties. These nanocomposite PAV-PC hydrogels showed strong antimicrobial activity towards Bacillus subtilis (G+ve) and Escherichia coli (G-ve).