Nasal administration of Carbamazepine using chitosan microspheres: In vitro/in vivo studies
Nasal administration of Carbamazepine using chitosan microspheres: In vitro/in vivo studies
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DOI：
10.1016/j.ijpharm.2005.09.013
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发表时间：
2006-01-03
影响因子：
5.8
通讯作者：
Giunchedi, P
中科院分区：
文献类型：
--
作者：
Gavini, E;Hegge, AB;Giunchedi, P
鼻腔途径既用于局部治疗，最近又用于全身给药以及肽和疫苗的输送。在本研究中，使用由盐酸壳聚糖（CH）或谷氨酸壳聚糖（CG）构成的微球对卡马西平（CBZ）的鼻腔给药进行了研究。还制备了空白微球作为比较。使用喷雾干燥技术生产微球，并对其形态（扫描电子显微镜，SEM）、药物含量、粒径（激光衍射法）和热行为（差示扫描量热法，DSC）进行表征。在磷酸盐缓冲液（pH 7.0）中进行体外药物释放研究。使用根据体外研究结果选择的含有壳聚糖谷氨酸的微粒在绵羊身上进行体内测试。将结果与单独鼻腔施用CBZ（原料）后获得的结果进行比较。为了评价体内数据，使用非配对t检验进行统计分析。喷雾干燥是制备CBZ负载微球的良好技术。与 CBZ 原料相比，将药物装载到聚合物网络中总是会导致溶出速率增加。使用壳聚糖谷氨酸获得的微球在体外和体内均具有最佳性能。与鼻腔给药纯药物相比，他们增加了血清中的药物浓度（微球和纯药物分别为 800 ng/ml 和 25 ng/ml）。所得结果表明壳聚糖谷氨酸微球中CBZ的负载增加了通过鼻子吸收的药物量。 (c) 2005 Elsevier B.V. 保留所有权利。
The nasal route is used both for local therapies and, more recently, for the systemic administration of drugs, as well as for the delivery of peptides and vaccines. In this study the nasal administration of Carbamazepine (CBZ) has been studied using microspheres constituted by chitosan hydrochloride (CH) or chitosan glutamate (CG). Blank microspheres were also prepared as a comparison. The microspheres were produced using a spray-drying technique and characterized in terms of morphology (scanning electron microscopy, SEM), drug content, particle-size (laser diffraction method) and thermal behaviour (differential scanning calorimetry, DSC). In vitro drug release studies were performed in phosphate buffer (pH 7.0). In vivo tests were carried out in sheep using the microparticles containing chitosan glutamate, chosen on the basis of the results of in vitro studies. The results were compared to those obtained after the nasal administration of CBZ (raw material) alone. For the evaluation of in vivo data statistical analysis was carried out using the unpaired t-test.Spray-drying was a good technique of preparation of CBZ-loaded microspheres. The loading of the drug into the polymeric network always led to an increase in the dissolution rate compared to CBZ raw material. The microspheres obtained using chitosan glutamate had the best behaviour both in vitro and in vivo. They increased the drug concentration in the serum when compared to the nasal administration of the pure drug (C,, 800 and 25 ng/ml for microspheres and pure drug, respectively). The results obtained indicate that the loading of CBZ in chitosan glutamate microspheres increases the amount of the drug absorbed through the nose. (c) 2005 Elsevier B.V. All rights reserved.