PDF(Pubmed)
Abstract：
Simvastatin (SIM) is widely prescribed to treat hyperlipidemia, despite its limitations, such as a short half-life and low oral bioavailability. To overcome these drawbacks, the development of a controlled-release formulation is desirable. This study aims to develop a microparticulate system based on cellulose acetate (ACT) obtained from Agave sisalana Perrine to promote a controlled SIM release. SIM-loaded microparticles (SMP) were prepared using the solvent emulsification-evaporation method. Several parameters were evaluated, including particle size, surface charge, morphology, encapsulation efficiency, thermochemical characteristics, crystallinity, and in vitro release profile. ACT exhibited favorable flow properties after acetylation, with a degree of substitution values superior to 2.5, as confirmed by both the chemical route and H-NMR, indicating the formation of cellulose triacetate. The obtained SMP were spherical with an average size ranging from 1842 to 1857 nm, a zeta potential of -4.45 mV, and a high SIM incorporation efficiency (98%). Thermal and XRD analyses revealed that SIM was homogeneously dispersed into the polymeric matrix in its amorphous state. In vitro studies using dialysis bags revealed that the controlled SIM release from microparticles was higher under simulated intestinal conditions and followed the Higuchi kinetic model. Our results suggest that ACT-based microparticles are a promising system for SIM delivery, which can improve its bioavailability, and result in better patient compliance.
摘要：
辛伐他汀（SIM）被广泛用于治疗高脂血症，尽管有其局限性,如短半衰期和低口服生物利用度。为了克服这些缺点，控释制剂的开发是合乎需要的。这项研究旨在开发一种基于从龙舌兰获得的醋酸纤维素（ACT）的微粒系统，以促进受控的SIM释放。使用溶剂乳化-蒸发法制备负载SIM的微粒(SMP)。评估了几个参数，包括颗粒大小，表面电荷,形态学,封装效率，热化学特性，结晶度和体外释放曲线。ACT在乙酰化后表现出良好的流动性能，取代度高于2.5，如化学路线和H-NMR所证实，表明三醋酸纤维素的形成。得到的SMP为平均尺寸为1842~1857nm的球形。zeta电位为-4.45mV，和高SIM掺入效率(98%)。热和XRD分析表明，SIM以无定形状态均匀地分散在聚合物基质中。使用透析袋的体外研究表明，在模拟的肠道条件下，微粒的受控SIM释放更高，并遵循Higuchi动力学模型。我们的结果表明，基于ACT的微粒是SIM递送的有前途的系统，可以提高其生物利用度，并导致更好的患者依从性。
