Department of Materials Science and Metallurgy, University of Cambridge, Cambridge, UK.
Ashland Specialties Ireland Ltd., National Science Park, Building V, Dublin Road, Petitswood, Mullingar, Co. Westmeath, Ireland.
Pharm Res. 2023 Jul;40(7):1697-1707. doi: 10.1007/s11095-022-03228-8. Epub 2022 Apr 26.
This paper investigates drug release from a novel series of mPEG-functionalised PLLA polymers whose individual components (PEG and PLLA) have regulatory FDA approval. Two processing methods were explored to understand their effect on the morphology and drug release profiles of the polymers, with and without mPEG functionalisation. In the first method the polymer and Propranolol.HCl drug powders were mixed together before injection moulding. In the second method, supercritical CO was used to mix the polymer and drug before injection moulding. When non-functionalised PLLA was processed through injection moulding alone, there were no signs of polymer-drug interaction, and the drug was confined to crystals on the surface. This resulted in up to 85 wt% burst release of propranolol.HCl after one day of incubation. By contrast, injection moulding of mPEG-functionalised polymers resulted in the partial dissolution of drug in the polymer matrix and a smaller burst (50 wt% drug) followed by sustained release. This initial burst release was completely eliminated from the profile of mPEG-functionalised polymers processed via supercritical CO. The addition of mPEG facilitated the distribution of the drug into the bulk matrix of the polymer. Paired with supercritical CO processing, the drug release profile showed a slow, sustained release throughout the 4 months of the study.
本文研究了一系列新型 mPEG 功能化 PLLA 聚合物的药物释放情况，这些聚合物的单体成分（PEG 和 PLLA）均获得了美国 FDA 的监管批准。本文探索了两种加工方法，以了解它们对聚合物形态和药物释放曲线的影响，这些聚合物有无 mPEG 功能化。在第一种方法中，聚合物和盐酸普萘洛尔药物粉末在注塑前混合在一起。在第二种方法中，超临界 CO 用于在注塑前混合聚合物和药物。当非功能化 PLLA 单独通过注塑加工时，没有聚合物-药物相互作用的迹象，药物被限制在表面的晶体上。这导致在孵育一天后，盐酸普萘洛尔的突释高达 85wt%。相比之下，mPEG 功能化聚合物的注塑加工导致药物部分溶解在聚合物基质中，突释（50wt%药物）较小，随后是持续释放。通过超临界 CO 加工的 mPEG 功能化聚合物的药物释放曲线完全消除了这种初始突释。mPEG 的添加促进了药物在聚合物基质中的分布。与超临界 CO 加工相结合，药物释放曲线在 4 个月的研究期间显示出缓慢、持续的释放。
