Combined Use of Cyclodextrins and Amino Acids for the Development of Cefixime Oral Solutions for Pediatric Use

Abstract

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 1H-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.

Design, Evaluation and Comparison of Nanostructured Lipid Carriers and Chitosan Nanoparticles as Carriers of Poorly Soluble Drugs to Develop Oral Liquid Formulations Suitable for Pediatric Use

“…The drug concentration to be loaded was determined considering its solubility in the formulation (see Section 3.1) and its minimum inhibitory concentration (MIC) necessary to exploit its antimicrobial activity. In a previous study [42], we found that the MIC of CEF against Escherichia coli is <0.5 µg/mL. Thus, even the lowest drug concentration used for NLCs loading (0.1 mg/mL) was more than 20 folds higher than its MIC value.…”

Palatability and Stability Studies to Optimize a Carvedilol Oral Liquid Formulation for Pediatric Use

“…One limitation of this study is that the human taste panel was conducted in healthy adults rather than children (who represent the target population) for a subsequent extrapolation of the results. As it is mentioned, for ethical reasons, conducting a clinical trial in children is quite complex [ 19 ].…”

“…Nevertheless, authorities recommend conducting palatability assessments involving children whenever feasible. When such assessments with children are not possible, taste screening by adult panels can serve as an alternative method, with the results examined for their applicability to children [ 19 ]. At this stage of development, we deemed an initial screening by an adult testing panel to be acceptable.…”

Investigation of the Affinity of Ceftobiprole for Selected Cyclodextrins Using Molecular Dynamics Simulations and HPLC

“…This me the covalent bonding structure has to be explicitly known before starting the sim however, most researchers perform their MD studies only with the neutral, nonform of the drug, which consequently limits the applicability of the obtained re pure aqueous, non-buffered solutions. A noteworthy exception was the recent w Cirri et al [13], who observed that the potential energies of the interaction betwe β-CD and cefixime differ by 75 kJ/mol (17.9 kcal/mol) depending on whether the…”