Galdón Eduardo, Millán-Jiménez Mónica, Mora-Castaño Gloria, de Ilarduya Antxon Martínez, Caraballo Isidoro
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Universidad de Sevilla, 41012 Seville, Spain.
Departament d'Enginyeria Química, Universitat Politècnica de Catalunya (ETSEIB), 08028 Barcelona, Spain.
Pharmaceutics. 2021 Jul 10;13(7):1057. doi: 10.3390/pharmaceutics13071057.
A biodegradable copolyester, poly(butylene succinate--ε-caprolactone) (PBS_CL), was used for first time as an excipient for pharmaceutical dosage forms using direct compression and hot processing techniques (ultrasound-assisted compression (USAC) and hot melt extrusion (HME)). Robust binary systems were achieved with hot processing techniques, allowing a controlled release of the drug. With only 12% / of PBS_CL, controlled release forms were obtained using USAC whereas in HME over 34% / of excipient is necessary. Amounts over 23% / allowed a long-extended release for more than 72 h following diffusional kinetic. Thanks to the high melting point of theophylline and the physicochemical properties of PBS_CL selected and synthesized, the structure of the excipient inside the USAC tablets and HME filaments corresponds to a continuum medium. A percolation threshold around 23% / was estimated, which agrees with a continuum percolation model. The polymer shows a high excipient efficiency value using HME and USAC. A nanostructured matrix with wall thicknesses lower than 0.1 µm was obtained. This leads to a very effective coating of the drug particles by the excipient, providing a slow and reproducible release. The present study therefore supports the use of PBS_CL, for the preparation of controlled release dosage forms using hot processing techniques.
一种可生物降解的共聚酯，聚（丁二酸丁二醇酯 - ε - 己内酯）（PBS_CL），首次被用作药物剂型的辅料，采用直接压片和热加工技术（超声辅助压片（USAC）和热熔挤出（HME））。通过热加工技术实现了稳定的二元体系，使药物能够控释。仅使用12%的PBS_CL，采用USAC就能获得控释剂型，而在HME中则需要超过34%的辅料。超过23%的用量在扩散动力学作用下可实现长达72小时以上的长效释放。由于茶碱的高熔点以及所选择和合成的PBS_CL的物理化学性质，USAC片剂和HME长丝内部辅料的结构对应于连续介质。估计渗滤阈值约为23%，这与连续渗滤模型相符。该聚合物在使用HME和USAC时表现出较高的辅料效率值。获得了壁厚低于0.1 µm的纳米结构基质。这导致辅料对药物颗粒的包覆非常有效，从而实现缓慢且可重现的释放。因此，本研究支持使用PBS_CL通过热加工技术制备控释剂型。
