Preparation of zolmitriptan-chitosan microparticles by spray drying for nasal delivery

被引:81
作者
Alhalaweh, Amjad [1 ]
Andersson, Staffan [1 ]
Velaga, Sitaram P. [1 ]
机构
[1] Lulea Univ Technol, Dept Hlth Sci, S-97187 Lulea, Sweden
关键词
Nasal delivery; Spray drying; Mucoadhesive; Zolmitriptan; Chitosan; GLASS-TRANSITION TEMPERATURE; MICROSPHERES; RELEASE; PERMEABILITY; ABSORPTION; TRANSPORT; CARRIER; DESIGN; LIQUID; SYSTEM;
D O I
10.1016/j.ejps.2009.07.003
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:206 / 214
页数:9
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