Rothen-Weinhold A, Besseghir K, Vuaridel E, Sublet E, Oudry N, Kubel F, Gurny R
University of Geneva, School of Pharmacy, Geneva, Switzerland.
Eur J Pharm Biopharm. 1999 Sep;48(2):113-21. doi: 10.1016/s0939-6411(99)00034-x.
Polylactic acid (PLA) is a biocompatible and biodegradable material with wide utility for many applications, including the design of controlled-release systems for pharmaceutical agents. The factors determining the degradation kinetics of these systems include the composition and the molecular mass of the polymer, the morphology and the structure of the device, and the influence of thermal processes. The processing of the polymer determines the structure and design of the device, and influences to a high degree its morphology, namely its microporous structure, polymeric chain orientation and crystallinity.In this work, we aimed to compare the influence of two different implant manufacturing techniques, extrusion and injection-molding, on the in vitro degradation of the polymeric matrix. Both kinds of implants were loaded with a somatostatin analogue. Decrease in molecular weight, and polydispersity evolution during an accelerated in vitro degradation test were studied by size exclusion chromatography. Morphological changes in the polymeric matrix during degradation were followed after defined time intervals by means of scanning electron microscopy. Crystallinity studies were performed by differential scanning calorimetry and by X-ray analysis. Peptide stability in the polymeric matrix after both manufacturing methods was evaluated. Peptide release profiles, obtained in vitro during a week dissolution test, from both implant samples, were studied. It was shown that both molecular weight and polydispersity decreased after extrusion or injection-molding. This decrease was more pronounced with the latter technique. Crystallinity studies demonstrated that the crystalline network was not destroyed after both manufacturing methods. Peptide release profiles obtained in vitro were in good accordance with scanning electron microscopy. It was found that both manufacturing techniques had to be considered, although the extruded implants degraded more rapidly in vitro than the injection-molded ones.
聚乳酸（PLA）是一种生物相容性和可生物降解的材料，在许多应用中具有广泛用途，包括药物控释系统的设计。决定这些系统降解动力学的因素包括聚合物的组成和分子量、装置的形态和结构以及热过程的影响。聚合物的加工决定了装置的结构和设计，并在很大程度上影响其形态，即其微孔结构、聚合物链取向和结晶度。在这项工作中，我们旨在比较两种不同的植入物制造技术，即挤出和注塑成型，对聚合物基质体外降解的影响。两种植入物都负载了生长抑素类似物。通过尺寸排阻色谱法研究了加速体外降解试验过程中分子量的降低和多分散性的演变。在规定的时间间隔后，通过扫描电子显微镜观察降解过程中聚合物基质的形态变化。通过差示扫描量热法和X射线分析进行结晶度研究。评估了两种制造方法后聚合物基质中肽的稳定性。研究了两种植入物样品在一周溶解试验期间体外获得的肽释放曲线。结果表明，挤出或注塑成型后分子量和多分散性均降低。后一种技术的这种降低更为明显。结晶度研究表明，两种制造方法后结晶网络均未被破坏。体外获得的肽释放曲线与扫描电子显微镜结果吻合良好。结果发现，虽然挤出的植入物在体外比注塑成型的植入物降解得更快，但两种制造技术都必须加以考虑。
