Pliva Croatia Ltd, Research and Development, Zagreb, Croatia.
Drug Dev Ind Pharm. 2011 Dec;37(12):1402-14. doi: 10.3109/03639045.2011.580350. Epub 2011 Jun 27.
The aim of this research was to design a controlled release, spray dried, mupirocin calcium-loaded microparticles (MP) with acrylic polymer and assess the influence of a feed solvent at preselected drug:polymer proportions (1:5 and 2:1 (w/w)) on the performance and stability of the prepared MP.
Physicochemical properties of MP were assessed using modulated differential scanning calorimetry (MDSC), and thermogravimetric analyses (TGA), Fourier transformed infrared spectroscopy (FTIR) and X-ray analyses and were correlated with drug release. Morphology and particle size were determined using low-angle laser light scattering and a scanning electron microscope. A time-kill assay was conducted on two strains of Staphylococcus aureus to evaluate the antimicrobial activity of MP.
The MP formed solid dispersions without apparent drug crystallization. Drug-polymer miscibility, morphology, drug release and consequently antimicrobial activity were dependent on drug loading (DL) and the used solvent. The superior control of drug release from MP was achieved for the higher DL (2:1 (w/w) drug:polymer proportion) using solvents in the following order: methanol ≈ methanol:ethanol (50:50, w/w) > isopropanol:acetone (40:60, w/w). Moreover, a time-kill assay performed on S. aureus (ATCC 29213) and methicillin-resistant S. aureus strains confirmed the prolonged release and preservation of antimicrobial activity of the microencapsulated drug. The physical aging of the solid dispersion after 10 months of storage had negligible impact on the MP performance.
Acrylic-based MP were confirmed as suitable microcarriers for prolonged drug release using a well-established spray drying technique, while solvent influence was strongly related to the DL employed.
本研究旨在设计一种载有莫匹罗星钙的丙烯酸聚合物控释喷雾干燥微球（MP），并评估在预选药物：聚合物比例（1:5 和 2:1（w/w））下，进料溶剂对所制备 MP 的性能和稳定性的影响。
使用调制差示扫描量热法（MDSC）和热重分析（TGA）、傅里叶变换红外光谱（FTIR）和 X 射线分析评估 MP 的物理化学性质，并将其与药物释放相关联。使用低角度激光光散射和扫描电子显微镜测定形态和粒径。对两种金黄色葡萄球菌菌株进行时间杀伤试验，以评估 MP 的抗菌活性。
MP 形成了无明显药物结晶的固体分散体。药物-聚合物的混溶性、形态、药物释放以及抗菌活性取决于药物载药量（DL）和所用溶剂。使用溶剂的顺序为：甲醇≈甲醇：乙醇（50:50，w/w）>异丙醇：丙酮（40:60，w/w），对于较高的 DL（2:1（w/w）药物：聚合物比例），可以更好地控制药物从 MP 中的释放。此外，对金黄色葡萄球菌（ATCC 29213）和耐甲氧西林金黄色葡萄球菌菌株进行的时间杀伤试验证实，微囊化药物的释放时间延长且保持了抗菌活性。经过 10 个月的储存后，固体分散体的物理老化对 MP 的性能几乎没有影响。
基于丙烯酸的 MP 被证实是一种适合于使用成熟的喷雾干燥技术延长药物释放的微载体，而溶剂的影响与所使用的 DL 密切相关。
