Yuliandra Yori, Zaini Erizal, Syofyan Syofyan, Pratiwi Wenny, Putri Lidiya Novita, Pratiwi Yuti Sahra, Arifin Helmi
Department of Pharmacology & Clinical Pharmacy, Faculty of Pharmacy, Andalas University, Padang 25163, Indonesia.
Department of Pharmaceutics, Faculty of Pharmacy, Andalas University, Padang 25163, Indonesia.
Sci Pharm. 2018 Jun 4;86(2):23. doi: 10.3390/scipharm86020023.
Ibuprofen is classified as a BCS class II drug which has low solubility and high permeability. We conducted the formation of the cocrystalline phase of ibuprofen with coformer nicotinamide to increase its solubility. The purpose of this study was to characterize the solid state of cocrystalline phase of ibuprofen-nicotinamide, determine the solubility, and evaluate its in vivo analgesic activity. The cocrystal of ibuprofen-nicotinamide was prepared by a slow evaporation method. The solid-state characterization was conducted by powder X-ray diffraction (PXRD) analysis, differential thermal analysis (DTA), and scanning electron microscopy (SEM). To investigate the in vivo analgesic activity, 28 male Swiss-Webster mice were injected with acetic acid 0.5% following oral administration of intact ibuprofen, physical mixture, and its cocrystalline phase with nicotinamide (equivalent to 26 mg/kg ibuprofen). The number of writhes was counted, and pain inhibition was calculated. All data were analyzed with one-way ANOVA followed by Duncan's Multiple Range Test (95% confidence interval). The results revealed that a new cocrystalline phase was successfully formed. The solubility testing showed that the cocrystal formation enhanced the solubility significantly as compared with the physical mixture and intact ibuprofen. A significant increase in the analgesic activity of cocrystal ibuprofen-nicotinamide was also confirmed.
布洛芬被归类为生物药剂学分类系统（BCS）的II类药物，其溶解度低但渗透性高。我们通过布洛芬与共形成剂烟酰胺形成共晶相来提高其溶解度。本研究的目的是表征布洛芬 - 烟酰胺共晶相的固态，测定其溶解度，并评估其体内镇痛活性。布洛芬 - 烟酰胺共晶通过缓慢蒸发法制备。通过粉末X射线衍射（PXRD）分析、差示热分析（DTA）和扫描电子显微镜（SEM）进行固态表征。为了研究体内镇痛活性，28只雄性瑞士韦伯斯特小鼠在口服完整布洛芬、物理混合物及其与烟酰胺的共晶相（相当于26mg/kg布洛芬）后注射0.5%的醋酸。记录扭体次数并计算疼痛抑制率。所有数据采用单因素方差分析，随后进行邓肯多重范围检验（95%置信区间）。结果表明成功形成了一种新的共晶相。溶解度测试表明，与物理混合物和完整布洛芬相比，共晶的形成显著提高了溶解度。布洛芬 - 烟酰胺共晶的镇痛活性也得到了显著提高。
