Breitkreutz Jörg, El-Saleh Firas, Kiera Christian, Kleinebudde Peter, Wiedey Wolfgang
Institute of Pharmaceutical Technology and Biopharmaceutics, Westphalien Wilhelms-University, Münster, Germany.
Eur J Pharm Biopharm. 2003 Sep;56(2):255-60. doi: 10.1016/s0939-6411(03)00090-0.
Sodium benzoate is used as a therapeutic agent in the treatment of some rare disorders that predominantly affect children. In preliminary investigations, liquid and semi-solid formulations of sodium benzoate failed because children refuse the oral uptake due to the bad taste of the drug. Recently developed microcapsules with macrogol as a hydrophilic binder raise concern in high-dose treatment regimens because acceptable daily intake limits are exceeded. A novel microcapsule formulation was developed consisting of a lipophilic core with high sodium benzoate load and a saliva-resistant coating. A new powder quality of saturated triglycerides from plant origin was introduced which complies with the Ph. Eur. monograph 'Hard fat'. Sodium benzoate and the triglyceride were mixed and directly extruded at room temperature. The extrudates were spheronized and coated in a fluidized-bed process. The resulting coated granules are small-sized microcapsules and taste neutrally. They can be mixed with food before administration. As the amount of released sodium benzoate is negligible within the first minutes, children do not recognize the bad taste and accept the medication. Recently, sodium benzoate in this novel formulation has been designated by the European Community as an orphan drug in the treatment of non-ketotic hyperglycinemia.
苯甲酸钠被用作治疗某些主要影响儿童的罕见疾病的治疗剂。在初步研究中，苯甲酸钠的液体和半固体制剂失败了，因为儿童由于药物的不良味道而拒绝口服。最近开发的以聚乙二醇作为亲水性粘合剂的微胶囊在高剂量治疗方案中引起了关注，因为超过了可接受的每日摄入量限制。开发了一种新型微胶囊制剂，其由具有高苯甲酸钠负载量的亲脂性核心和抗唾液涂层组成。引入了一种符合欧洲药典专论“硬脂”的植物来源饱和甘油三酯的新粉末质量。将苯甲酸钠和甘油三酯混合并在室温下直接挤出。将挤出物滚圆并在流化床过程中进行包衣。所得的包衣颗粒是小尺寸的微胶囊，味道中性。它们可以在给药前与食物混合。由于在最初几分钟内释放的苯甲酸钠量可以忽略不计，儿童不会察觉到不良味道并接受药物治疗。最近，这种新型制剂中的苯甲酸钠已被欧洲共同体指定为治疗非酮症高甘氨酸血症的孤儿药。
