Kislalioglu M S, Khan M A, Blount C, Goettsch R W, Bolton S
College of Pharmacy, University of Rhode Island, Kingston 02881.
J Pharm Sci. 1991 Aug;80(8):799-804. doi: 10.1002/jps.2600800820.
Ibuprofen:Eudragit coprecipitates were prepared in 10:3 ratios and their physical properties and related dissolution characteristics were determined. The Eudragit polymers used for the studies were three anionics (Eudragit L100, Eudragit L100-55, and Eudragit S-100), one anionic:cationic mixture used in a 1:1 ratio (Eudragit S100 + E100), and four zwitterionics (Eudragits RL 100, RS 100, RSPM, and RLPM). Physical characterizations were made using qualitative and quantitative X-ray diffractometry, IR spectrophotometry, and differential scanning calorimetry (DSC). Except for Eudragit S100 + E100 coprecipitates, no sizeable interaction at a molecular level was detected between the drug and the polymer. The crystalline structure of the drug was slightly modified in the coprecipitates. Regardless of the lack of interaction, dissolution of ibuprofen was retarded from all the coprecipitates studied (except Eudragit L100), especially in the pH 6.8 to 7.5 media in which the drug is freely soluble. The dissolution rate constants of the coprecipitates, calculated using Higuchi equation, demonstrated that dissolution decreased in the order of anionics greater than zwitterionic greater than anionic + cationic mixtures. The data obtained suggest that the release mechanisms involved are the swelling and slower dissolution of the polymer matrix relative to precipitated ibuprofen. The coprecipitates possess improved flow properties compared with ibuprofen with the exception of Eudragit RLPM and Eudragit RSPM. Eudragit coprecipitates can be useful tools in preparing ibuprofen sustained-release tablets. The coprecipitation technique used is simple and minimizes the use of organic solvents.
以10:3的比例制备了布洛芬与丙烯酸树脂共沉淀物,并测定了它们的物理性质和相关的溶出特性。用于该研究的丙烯酸树脂聚合物有三种阴离子型(丙烯酸树脂L100、丙烯酸树脂L100 - 55和丙烯酸树脂S - 100)、一种以1:1比例使用的阴离子型与阳离子型混合物(丙烯酸树脂S100 + E100)以及四种两性离子型(丙烯酸树脂RL 100、RS 100、RSPM和RLPM)。使用定性和定量X射线衍射法、红外分光光度法和差示扫描量热法(DSC)进行了物理表征。除了丙烯酸树脂S100 + E100共沉淀物外,未检测到药物与聚合物之间在分子水平上有显著相互作用。在共沉淀物中,药物的晶体结构略有改变。尽管缺乏相互作用,但在所研究的所有共沉淀物(除丙烯酸树脂L100外)中,布洛芬的溶出均受到延迟,尤其是在pH 6.8至7.5的介质中,该药物在其中可自由溶解。使用Higuchi方程计算的共沉淀物的溶出速率常数表明,溶出度降低的顺序为阴离子型大于两性离子型大于阴离子型 + 阳离子型混合物。所获得的数据表明,涉及的释放机制是聚合物基质相对于沉淀的布洛芬的溶胀和较慢的溶解。除了丙烯酸树脂RLPM和丙烯酸树脂RSPM外,共沉淀物与布洛芬相比具有改善的流动性。丙烯酸树脂共沉淀物可作为制备布洛芬缓释片的有用工具。所采用的共沉淀技术简单,且最大限度地减少了有机溶剂的使用。