Prodduturi Suneela, Manek Rahul V, Kolling William M, Stodghill Steven P, Repka Michael A
Food and Drug Administration, Division of Pharmaceutical Analysis, St. Louis, Missouri 63101, USA.
J Pharm Sci. 2005 Oct;94(10):2232-45. doi: 10.1002/jps.20437.
Poly(ethylene oxide) (PEO) was used to prepare thin polymer films containing clotrimazole (CT) utilizing hot-melt extrusion (HME) technology. Films containing PEOs of two different molecular weights and the drug were investigated for solid-state characteristics, moisture-sorption, bioadhesivity, mechanical properties, release characteristics, and physical and chemical stability of the drug within the HME films. The solid-state characterization of the drug and the polymer were performed utilizing differential scanning calorimetry and X-ray diffractometry. A Texture analyzer was utilized to study the bioadhesive and mechanical properties of the HME films. Physical and chemical stability of the films, stored at 25 degrees C/60% RH, was studied for up to 12 months. XRD profiles indicated that the drug was physically unstable (recrystallization of the drug occurred) after storage for 3 months at 25 degrees C/60% RH. Based on the DSC studies, it has been proposed that the recrystallization of the drug may be due to the folding (due to HME) and unfolding (upon storage) of the linear PEO chains. Desirable bioadhesive, mechanical, and thermoplastic properties of PEO qualify it as a promising and potential drug carrier. However, further investigation is necessary to enhance the physical stability of these PEO-drug systems.
聚环氧乙烷（PEO）被用于利用热熔挤出（HME）技术制备含有克霉唑（CT）的聚合物薄膜。研究了含有两种不同分子量的PEO以及药物的薄膜的固态特性、吸湿性能、生物黏附性、机械性能、释放特性以及药物在HME薄膜中的物理和化学稳定性。利用差示扫描量热法和X射线衍射法对药物和聚合物进行固态表征。使用质地分析仪研究HME薄膜的生物黏附性和机械性能。对在25℃/60%相对湿度下储存长达12个月的薄膜的物理和化学稳定性进行了研究。X射线衍射图谱表明，在25℃/60%相对湿度下储存3个月后，药物在物理上不稳定（发生了药物重结晶）。基于差示扫描量热法研究，有人提出药物的重结晶可能是由于线性PEO链的折叠（由于HME）和解折叠（储存时）。PEO具有理想的生物黏附性、机械性能和热塑性，使其成为一种有前途和潜力的药物载体。然而，有必要进一步研究以提高这些PEO-药物系统的物理稳定性。
