Mucoadhesive microspheres for nasal administration of an antiemetic drug, metoclopramide: in-vitro/ex-vivo studies
Mucoadhesive microspheres for nasal administration of an antiemetic drug, metoclopramide: in-vitro/ex-vivo studies
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DOI：
10.1211/0022357055623
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发表时间：
2005-03-01
影响因子：
3.3
通讯作者：
Giunchedi, P
中科院分区：
文献类型：
--
作者：
Gavini, E;Rassu, G;Giunchedi, P
制备了用于鼻腔给药止吐药盐酸甲氧氯普胺的微粒给药系统。使用喷雾干燥法获得由海藻酸钠、壳聚糖盐酸盐或两者组成的微球;制备一些批次的无药物微粒作为比较。对微球的形态、体外溶胀行为、粘膜粘附性能和药物释放进行了评价。采用绵羊鼻粘膜进行离体药物渗透试验，并以药物溶液的渗透试验作为对照。在离体渗透试验期间，在鼻粘膜上进行透射电子显微镜（TEM）分析以研究上皮细胞和紧密连接的形态学变化，同时使用光立体显微镜（PM）检查微球形态学的变化。喷雾干燥的微粒具有约3-10 μ m的平均直径（d（vs））。它们表现出良好的体外粘膜粘附特性。体外释放曲线和溶胀行为取决于其组成：药物释放发生在1-3小时。离体研究表明，通过粘膜的药物渗透从基于壳聚糖的微粒是高于从那些由单独的藻酸盐。这可能与壳聚糖的渗透增强特性有关。壳聚糖与海藻酸钠的复合导致药物释放的控制。在渗透试验过程中微球的显微镜观察显示，微粒溶胀和胶凝，保持其形状。暴露于由藻酸盐/壳聚糖组成的微粒后的粘膜的TEM分析显示开放的紧密连接。初步研究表明，海藻酸盐/壳聚糖喷雾干燥微球具有良好的特性，可用作止吐药物的鼻粘膜粘附载体。
Microparticulate delivery systems designed for the nasal administration of an antiemetic drug, metoclopramide hydrochloride, were prepared. Microspheres composed of sodium alginate, chitosan hydrochloride, or both, were obtained using a spray-drying method; some batches of drug-free microparticles were prepared as a comparison. The morphology, in-vitro swelling behaviour, mucoadhesive properties and drug release from microparticles were evaluated. Ex-vivo drug permeation tests were carried out using sheep nasal mucosa; permeation test of the drug solution was peformed as comparison. During ex-vivo permeation tests, transmission electron microscopy (TEM) analyses were carried out on the nasal mucosa to study the morphological changes of epithelial cells and tight junctions, while the change in microsphere morphology was examined using photostereo, microscopy (PM). Spray-dried microparticles had a mean diameter (d(vs)) in the range of about 3-10 mu m. They showed good in-vitro mucoadhesive properties. In-vitro release profiles and swelling behaviour depended on their composition: the drug release occurred in 1-3 h. Ex-vivo studies showed that drug permeation through the mucosa from microparticles based on chitosan was higher than from those consisting of alginate alone. This can be related to the penetration enhancing properties of chitosan. Complexation of chitosan with alginate led to a control of the drug release. Microscopy observation of microspheres during the permeation tests revealed that microparticles swelled and gelled, maintaining their shape. TEM analyses of the mucosa after exposure to the microparticles consisting of alginate/chitosan showed opened tight junctions. This preliminary study shows that alginate/chitosan spray-dried microspheres have promising properties for use as mucoadhesive nasal carriers of an antiemetic drug.