Department of Health Sciences, Luleå University of Technology, 97187 Luleå, Sweden.
Eur J Pharm Sci. 2009 Oct 8;38(3):206-14. doi: 10.1016/j.ejps.2009.07.003. Epub 2009 Jul 16.
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 microparticles 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.
本研究的目的是使用喷雾干燥技术制备佐米曲普坦（一种治疗偏头痛的药物）与天然聚合物壳聚糖的鼻用黏附性干粉。还研究了壳聚糖的类型、分子量和比例对粉末和颗粒特性的影响。制备了含有不同比例壳聚糖的溶液并进行喷雾干燥。通过高效液相色谱法（HPLC）测定药物的化学稳定性和含量。还确定了微粒子的形态和粒径范围。使用热分析（DSC/MDSC 和 TGA）、粉末 X 射线衍射（PXRD）和傅里叶变换红外光谱（FT-IR）进行了固态分析。研究了药物释放曲线，并比较了达到最大溶液浓度（T(max)）所需的时间。药物化学性质稳定，微粒子中载药量为 93-105%。微粒子为球形，粒径分布较窄，与配方无关。无论配方如何，当壳聚糖含量低于 90%（w/w）时，均观察到相分离。相比之下，在含有 90%（w/w）壳聚糖的配方中，药物呈分子分散状态。FT-IR 研究表明，当佐米曲普坦为无定形时，对应于分子间氢键的谱带更宽且更弥散。还观察到药物与壳聚糖之间形成氢键。随着壳聚糖比例的降低，T(max)增加，在含有 90%（w/w）壳聚糖的配方中，T(max)与配方中壳聚糖的分子量成正比。喷雾干燥是一种适合制备佐米曲普坦和壳聚糖鼻用黏附性干粉的技术。药物的分散和释放受壳聚糖性质和组成的影响。
