Blasi Paolo, Schoubben Aurélie, Giovagnoli Stefano, Perioli Luana, Ricci Maurizio, Rossi Carlo
Department of Chemistry and Technology of Drugs, University of Perugia, Perugia, Italy.
AAPS PharmSciTech. 2007 May 11;8(2):Article 37. doi: 10.1208/pt0802037.
The aim of this work was to provide an understanding of the interaction occurring between ketoprofen and poly(lactic-co-glycolic acid) (PLGA) that leads to polymer plasticization. Experimental glass transition temperature (Tg) values were fitted with the theoretical ones predicted by the Fox and Gordon-Taylor/Kelley-Bueche equations. PLGA films containing different amounts of ketoprofen (KET) were prepared by solvent casting and characterized by scanning electron microscopy, differential scanning calorimetry, and Fourier transform infrared spectroscopy (FTIR). Differential scanning calorimetry evidenced that KET acted as a plasticizer in a similar biphasic way in both end-capped and uncapped PLGA. At KET contents of 20% to 35%, depending on the investigated polymer, the Tg was around 23 degrees C. Higher KET amounts did not lower further the Tg, and the excess of drug was found to crystallize into the polymeric matrix. Experimental Tg's deviated negatively from the predicted ones probably because of hydrogen bonding. The FTIR spectra of the films, loaded with different amounts of KET, showed a shift to higher wavenumbers for the peaks at 1697 and 1655 cm(-1) confirming the presence of some interactions, probably hydrogen bonds between the ketoprofen carboxylic group and the PLGA carbonyl groups along the polymer backbone. The hydrogen bonding between KET and PLGA is probably responsible for KET plasticizing effect. KET behaving as a lubricant may disrupt polymer chain-chain interactions, removing additional barriers to bond rotation and chain mobility.
这项工作的目的是了解酮洛芬与聚乳酸-乙醇酸共聚物(PLGA)之间发生的相互作用,这种相互作用会导致聚合物增塑。将实验测得的玻璃化转变温度(Tg)值与由福克斯方程以及戈登-泰勒/凯利-比彻方程预测的理论值进行拟合。通过溶液浇铸法制备了含有不同量酮洛芬(KET)的PLGA薄膜,并通过扫描电子显微镜、差示扫描量热法和傅里叶变换红外光谱(FTIR)对其进行表征。差示扫描量热法证明,在封端和未封端的PLGA中,KET均以类似的双相方式起到增塑剂的作用。根据所研究的聚合物不同,当KET含量为20%至35%时,Tg约为23摄氏度。更高的KET含量并未进一步降低Tg,且发现过量的药物在聚合物基质中结晶。实验测得的Tg值可能由于氢键作用而与预测值呈负偏差。不同KET含量薄膜的FTIR光谱显示,1697和1655 cm⁻¹处的峰向更高波数移动,这证实了存在一些相互作用,可能是酮洛芬羧基与聚合物主链上PLGA羰基之间形成了氢键。KET与PLGA之间的氢键作用可能是KET增塑作用的原因。KET作为润滑剂可能会破坏聚合物链间的相互作用,消除键旋转和链迁移的额外障碍。