Department of Pharmaceutical Technology, College of Pharmacy, Tanta University, 4111 Tanta, Egypt.
Department of Pharmaceutical Technology, College of Pharmacy, Tanta University, 4111 Tanta, Egypt.
Int J Pharm. 2019 May 30;563:395-405. doi: 10.1016/j.ijpharm.2019.04.024. Epub 2019 Apr 9.
Fast dissolution of nonsteroidal anti-inflammatory drugs (NSAIDs) is a prerequisite from patient perspective. However, most NSAIDs are slowly dissolving acidic compounds. Caffeine, a commonly used analgesic adjuvant with NSAIDs showed high potential as eutectic co-former for acidic compounds. The study investigated eutectic forming potential of caffeine with meloxicam, aceclofenac and flurbiprofen. Each drug was co-ground with caffeine in various ratios and the products were characterized by thermal analysis to determine the optimum eutectic composition from phase diagram and Tamman's triangle. The optimum systems were subjected to X-ray powder diffraction (XRPD), Fourier-transform infrared (FTIR) and dissolution studies. Co-ground systems at dose ratio were also assessed for drug dissolution and anti-inflammatory effect using carrageenan induced rat paw edema method. Eutexia was confirmed by thermal analysis with the optimum composition being 1:1, 1:1 and 1:2 (NSAID: caffeine) for aceclofenac, flurbiprofen and meloxicam, respectively. Eutexia did not alter FTIR spectra with minor changes being recorded in XRPD patterns. The eutectic systems underwent fast liberation of drugs with fast dissolution being retained even at dose ratios. Dissolution enhancement was associated with enhanced anti-inflammatory response. The study introduced caffeine as eutectic forming analgesic for fixed dose combination with NSAIDs to enhance drug dissolution and anti-inflammatory effect.
快速溶解非甾体抗炎药（NSAIDs）是从患者角度出发的前提条件。然而，大多数 NSAIDs 是缓慢溶解的酸性化合物。咖啡因是一种常用的镇痛辅助剂，与 NSAIDs 结合具有很高的形成共晶的潜力，可作为酸性化合物的共晶形成剂。本研究调查了咖啡因与美洛昔康、醋氯芬酸和氟比洛芬形成共晶的潜力。将每种药物与咖啡因以不同比例共研磨，并通过热分析对产物进行表征，从相图和 Tamman 三角确定最佳共晶组成。对最佳体系进行 X 射线粉末衍射（XRPD）、傅里叶变换红外（FTIR）和溶解研究。还使用角叉菜胶诱导的大鼠足肿胀法评估共研磨系统在剂量比下的药物溶解和抗炎效果。通过热分析证实了共晶，最佳组成分别为 1:1、1:1 和 1:2（NSAID：咖啡因）用于醋氯芬酸、氟比洛芬和美洛昔康。共晶没有改变 FTIR 光谱，XRPD 图谱上只记录了微小的变化。共晶系统迅速释放药物，即使在剂量比下也能保持快速溶解。溶解增强与增强的抗炎反应有关。该研究介绍了咖啡因作为固定剂量组合与 NSAIDs 形成共晶的镇痛剂，以增强药物溶解和抗炎作用。
