Ravina-Eirin Elena, Gomez-Amoza J L, Martínez-Pacheco Ramón
Departamento de Farmacia y Tecnología Farmacéutica, Universidad de Santiago de Compostela , Santiago de Compostela , Spain.
Drug Dev Ind Pharm. 2015 Jun;41(6):1000-5. doi: 10.3109/03639045.2014.922572. Epub 2014 May 30.
The objective of this study is to evaluate the dissolution of a poorly soluble drug (prednisolone) from different sized matricial particles (from <250 to >1500 µm) with two drug contents (10% or 20%) obtained by hot melt extrusion using the hyperbranched polyesteramide Hybrane S1200 (water-soluble and with a Tg of 45 °C) as the carrier. X-ray diffraction, differential scanning calorimetry and SEM studies permit us to conclude that in 10% prednisolone extrudate, the drug is mainly dispersed within the carrier, whereas in those containing 20% an important fraction of the drug remains in a crystalline state and is accumulated on the surface of the extrudates. On particles proceeding from 10% drug extrudate, the drug dissolution rate is very high and slightly dependant on particle size and in all cases, higher than the pure micronized drug. However, on particles proceeding from 20% prednisolone extrudate particle size have a major effect on drug dissolution rate, attributable to higher proportions of crystalline drug accumulated on the surface, hindering polymer dissolution. Thus, the reduction of the particle size after extrudate grinding creates new surfaces from inside, that leads to strong increments on prednisolone dissolution rate, and becomes higher than the pure micronized drug one when the particle size is <250 µm.
本研究的目的是评估难溶性药物（泼尼松龙）从不同尺寸（小于250至大于1500 µm）的基质颗粒中溶出的情况，这些颗粒具有两种药物含量（10%或20%），通过热熔挤出法制备，使用超支化聚酯酰胺Hybrane S1200（水溶性，玻璃化转变温度为45 °C）作为载体。X射线衍射、差示扫描量热法和扫描电子显微镜研究使我们得出结论，在10%泼尼松龙挤出物中，药物主要分散在载体内，而在含有20%药物的挤出物中，有相当一部分药物仍处于结晶状态，并积聚在挤出物表面。对于由10%药物挤出物制成的颗粒，药物溶出率非常高，且对粒径的依赖性较小，在所有情况下均高于纯微粉化药物溶出率。然而，对于由20%泼尼松龙挤出物制成的颗粒，粒径对药物溶出率有重大影响，这归因于表面积累的结晶药物比例较高，阻碍了聚合物的溶解。因此，挤出物研磨后粒径的减小会从内部产生新的表面，这导致泼尼松龙溶出率大幅提高，当粒径小于250 µm时，溶出率高于纯微粉化药物溶出率。
