Bogataj M, Mrhar A, Grabnar I, Rajtman Z, Bukovec P, Srcic S, Urleb U
Faculty of Pharmacy, University of Ljubljana, Slovenia.
J Microencapsul. 2000 Jul-Aug;17(4):499-508. doi: 10.1080/026520400405741.
Microspheres containing the mucoadhesive polymer chitosan hydrochloride, with matrix polymer Eudragit RS, pipemidic acid as a model drug and agglomeration preventing agent magnesium stearate were prepared by the solvent evaporation method. The amount of magnesium stearate was varied and the following methods were used for microsphere evaluation: sieve analysis, drug content and dissolution determination, scanning electron microscopy, x-ray diffractometry, DSC and FTIR spectroscopy. The results showed that average particle size decreased with increasing amount of magnesium stearate used for microsphere preparation. This is probably a consequence of stabilization of the emulsion droplets with magnesium stearate. Higher pipemidic acid content in the microspheres was observed in larger particle size fractions and when higher amounts of magnesium stearate were used. It was also found that these two parameters significantly influenced the dissolution rate. The important reason for the differences in drug content in microspheres of different particle sizes is the diffusion of pipemidic acid from the acetone droplets in liquid paraffin during the preparation procedure. The physical state of pipemidic acid changed from crystalline to mostly amorphous with its incorporation in microspheres, as shown by x-ray diffractometry and differential scanning calorimetry. No differences were observed in the physical state of pipemidic acid and in microsphere shape and surface between different size fractions of microspheres, prepared with different amounts of magnesium stearate. Additionally, no correlation between the physical state of the drug in different microspheres and their biopharmaceutical properties was found.
采用溶剂蒸发法制备了含有黏附性聚合物盐酸壳聚糖的微球，基质聚合物为丙烯酸树脂Eudragit RS，以吡哌酸作为模型药物，硬脂酸镁作为抗团聚剂。改变硬脂酸镁的用量，并采用以下方法对微球进行评价：筛分分析、药物含量及溶出度测定、扫描电子显微镜、X射线衍射、差示扫描量热法和傅里叶变换红外光谱法。结果表明，随着用于微球制备的硬脂酸镁用量增加，平均粒径减小。这可能是硬脂酸镁使乳液滴稳定的结果。在较大粒径级分的微球中以及使用较高量硬脂酸镁时，观察到微球中吡哌酸含量较高。还发现这两个参数显著影响溶出速率。不同粒径微球中药物含量存在差异的重要原因是制备过程中吡哌酸从液体石蜡中的丙酮滴中扩散。如X射线衍射和差示扫描量热法所示，吡哌酸掺入微球后，其物理状态从结晶态变为主要为非晶态。在用不同量硬脂酸镁制备的不同粒径级分的微球之间，未观察到吡哌酸的物理状态、微球形状和表面存在差异。此外，未发现不同微球中药物的物理状态与其生物药剂学性质之间存在相关性。
