Jelvehgari Mitra, Atapour Fatemeh, Nokhodchi Ali
Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
Arch Pharm Res. 2009 Jul;32(7):1019-28. doi: 10.1007/s12272-009-1707-y. Epub 2009 Jul 31.
The present research work compares the effect of microsphere preparation technique on micromeritics and release behaviors of theophylline microspheres. Microspheres were prepared by oil-in oil (O(1)/O(2)) emulsion solvent evaporation method (ESE) using different ratios of anhydrous theophylline to cellulose acetate butyrate (CAB). Cyclohexane was used as non-solvent to modify the ESE technique (MESE method) and the effect of non-solvent volume on properties of microspheres was investigated. The obtained microspheres were analyzed in terms of drug content, particle size and encapsulation efficiency. The morphology of microsphere was studied using scanning electron microscope. The solid state of microspheres, theophylline and CAB were investigated using X-ray, FT-IR and DSC. The drug content of microspheres prepared by MESE method was significantly lower (15.54% +/- 0.46) than microspheres prepared by ESE method (41.08 +/- 0.40%). The results showed that as the amount of cyclohexane was increased from 2 mL to 6 mL the drug content of microspheres was increased from 15.54% to 28.71%. Higher encapsulation efficiencies were obtained for microspheres prepared by ESE method (95.87%) in comparison with MESE method (64.71%). Mean particle size of microsphere prepared by ESE method was not remarkably affected by drug to polymer ratio, whereas in MSES method when the volume of cyclohexane was increased the mean particle size of microsphere was significantly decreased. The ratio of drug to polymer significantly changed the rate of drug release from microspheres and the highest drug release was obtained for the microsphere with high drug to polymer ratio. The amount of cyclohexane did not significantly change the drug release. Although, x-ray showed a small change in crystallinity of theophylline in microspheres, DSC results proved that theophylline in microspheres is in amorphous state. No major chemical interaction between the drug and polymer was reported during the encapsulation process.
本研究工作比较了微球制备技术对茶碱微球的粉体学性质和释放行为的影响。采用油包油（O(1)/O(2)）乳液溶剂蒸发法（ESE），使用不同比例的无水茶碱与醋酸丁酸纤维素（CAB）制备微球。以环己烷作为非溶剂对ESE技术进行改进（MESE法），并研究了非溶剂体积对微球性质的影响。对所得微球进行药物含量、粒径和包封率分析。使用扫描电子显微镜研究微球的形态。利用X射线、傅里叶变换红外光谱（FT-IR）和差示扫描量热法（DSC）研究微球、茶碱和CAB的固态。MESE法制备的微球的药物含量（15.54%±0.46）显著低于ESE法制备的微球（41.08±0.40%）。结果表明，随着环己烷用量从2 mL增加到6 mL，微球的药物含量从15.54%增加到28.71%。与MESE法（64.71%）相比，ESE法制备的微球具有更高的包封率（95.87%）。ESE法制备的微球的平均粒径受药物与聚合物比例的影响不显著，而在MSES法中，当环己烷体积增加时，微球的平均粒径显著减小。药物与聚合物的比例显著改变了微球的药物释放速率，药物与聚合物比例高的微球药物释放量最高。环己烷的用量未显著改变药物释放。尽管X射线显示微球中茶碱的结晶度有微小变化，但DSC结果证明微球中的茶碱处于非晶态。在包封过程中未报道药物与聚合物之间有主要的化学相互作用。
