Preparation of zolmitriptan-chitosan microparticles by spray drying for nasal delivery
Preparation of zolmitriptan-chitosan microparticles by spray drying for nasal delivery
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DOI：
10.1016/j.ejps.2009.07.003
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发表时间：
2009-10-08
影响因子：
4.6
通讯作者：
Velaga, Sitaram P.
中科院分区：
文献类型：
--
作者：
Alhalaweh, Amjad;Andersson, Staffan;Velaga, Sitaram P.
本研究的目的是使用喷雾干燥制备粘膜粘附干粉的抗偏头痛药物，佐米曲坦，结合天然聚合物，壳聚糖，用于鼻腔给药。研究了壳聚糖的种类、分子量和配比对粉末和颗粒特性的影响。制备含有不同比例壳聚糖的溶液并喷雾干燥。采用高效液相色谱法测定药物的化学稳定性和含量。还测定了微粒的形态和尺寸范围。采用热分析法（DSC/MDSC和TGA）、粉末X射线衍射（PXRD）和傅里叶变换红外光谱（FT-IR）进行固态分析。研究了药物释放曲线，并使用达到最大溶液浓度所需的时间（Tmax）进行比较。该药物是化学稳定的，在微粒中的载量为93-105%。微粒是球形的，具有窄的尺寸分布，与制剂无关。对于含有少于90%（w/w）壳聚糖的制剂，观察到相分离，而与类型无关。相反，在含有90%（w/w）壳聚糖的制剂中，药物以分子形式分散。FT-IR研究表明，对应于分子间氢键的谱带更宽，更分散时佐米曲坦是无定形的。药物和壳聚糖之间形成氢键也被观察到。Tmax随着壳聚糖比例的降低而增加，并且在含有90%（w/w）壳聚糖的制剂中与壳聚糖的分子量成比例。喷雾干燥是制备用于鼻腔应用的佐米曲坦和壳聚糖的粘膜粘附干粉的合适技术。壳聚糖的性质和组成影响药物的分散和释放。(C)2009 Elsevier B. V.保留所有权利。
The objective of this study was to use spray drying to prepare mucoadhesive dry powders of the antimigraine drug, zolmitriptan, in combination with the natural polymer, chitosan, for nasal administration. The effect of type, molecular weight, and proportion of chitosan on the powder and particle characteristics was also studied. Solutions containing different proportions of chitosans were prepared and spray dried. The chemical stability and content of the drug were determined by HPLC. The morphology and size range of the rnicroparticles were also determined. Solid-state analysis was undertaken using thermal methods (DSC/MDSC and TGA), powder X-ray diffraction (PXRD), and Fourier transform infra-red spectroscopy (FT-IR). The drug release profiles were investigated and the time required to reach maximum solution concentrations (T-max) was used for comparison. The drug was chemically stable, with a 93-105% loading in the microparticles. The microparticles were spherical with a narrow size distribution, irrespective of the formulation. Phase separation was observed for formulations containing less than 90% (w/w) chitosan, irrespective of the type. In contrast, in the formulation containing 90% (w/w) chitosan, the drug was molecularly dispersed. FT-IR studies showed that the bands corresponding to intermolecular hydrogen bonding were broader and more diffuse when zolmitriptan was amorphous. The formation of a hydrogen bond between drug and chitosans was also observed. T-max increased as the proportion of chitosan decreased, and was proportional to the molecular weight of the chitosan in the formulation containing 90% (w/w) chitosan. Spray drying is a suitable technique for making mucoadhesive dry powders of zolmitriptan and chitosan for nasal application. The dispersion and release of the drug was affected by the properties and composition of the chitosan. (C) 2009 Elsevier B.V. All rights reserved.