Cirri Marzia, Mennini Natascia, Nerli Giulia, Rubia Jessica, Casalone Enrico, Melani Fabrizio, Maestrelli Francesca, Mura Paola
Department of Chemistry, University of Florence, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy.
Department of Biology, University of Florence, Via Madonna del Piano 6, 50019 Sesto Fiorentino, Italy.
Pharmaceutics. 2021 Nov 13;13(11):1923. doi: 10.3390/pharmaceutics13111923.
Cefixime (CEF) is a cephalosporin included in the WHO Model List of Essential Medicines for Children. Liquid formulations are considered the best choice for pediatric use, due to their great ease of administration and dose-adaptability. Owing to its very low aqueous solubility and poor stability, CEF is only available as a powder for oral suspensions, which can lead to reduced compliance by children, due to its unpleasant texture and taste, and possible non-homogeneous dosage. The aim of this work was to develop an oral pediatric CEF solution endowed with good palatability, exploiting the solubilizing and taste-masking properties of cyclodextrins (CDs), joined to the use of amino acids as an auxiliary third component. Solubility studies indicated sulfobutylether-β-cyclodextrin (SBEβCD) and Histidine (His) as the most effective CD and amino acid, respectively, even though no synergistic effect on drug solubility improvement by their combined use was found. Molecular Dynamic and H-NMR studies provided insight into the interactions of binary CEF:His and ternary CEF:His:SBEβCD systems used to prepare CEF solutions, which resulted stable and maintained unchanged antimicrobial activity during the two-weeks-use in therapy. The ternary solution was superior in terms of more tolerable pH (5.6 vs. 4.7) and better palatability, being resulted completely odorless by a panel test.
头孢克肟（CEF）是世界卫生组织儿童基本药物示范清单中包含的一种头孢菌素。液体制剂被认为是儿科用药的最佳选择，因为其易于给药且剂量适应性强。由于CEF的水溶性极低且稳定性差，它仅以口服混悬剂粉末形式提供，这可能会导致儿童依从性降低，因为其质地和味道不佳，且可能存在剂量不均匀的情况。这项工作的目的是开发一种具有良好适口性的儿科口服CEF溶液，利用环糊精（CDs）的增溶和掩味特性，并结合使用氨基酸作为辅助第三成分。溶解度研究表明，磺丁基醚-β-环糊精（SBEβCD）和组氨酸（His）分别是最有效的CD和氨基酸，尽管未发现它们联合使用对提高药物溶解度有协同作用。分子动力学和H-NMR研究深入了解了用于制备CEF溶液的二元CEF:His和三元CEF:His:SBEβCD系统的相互作用，该溶液在治疗两周使用期间稳定且抗菌活性保持不变。三元溶液在更可耐受的pH值（5.6对4.7）和更好的适口性方面更具优势，经小组测试结果完全无味。
