Rat Palatability Study for Taste Assessment of Caffeine Citrate Formulation Prepared via Hot-Melt Extrusion Technology

Developing a pediatric oral formulation with an age-appropriate dosage form and taste masking of naturally bitter active pharmaceutical ingredients (APIs) are key challenges for formulation scientists. Several techniques are used for taste masking of bitter APIs to improve formulation palatability; however, not all the techniques are applicable to pediatric dosage forms because of the limitations on the kind and concentration of the excipients that can be used. Hot-melt extrusion (HME) technology is used successfully for taste masking of bitter APIs and overcomes some of the limitations of the existing taste-masking techniques. Likewise, analytical taste assessment is an important quality control parameter evaluated by several in vivo and in vitro methods, such as the human taste panel, electrophysiological methods, electronic sensor, and animal preference tests to aid in selecting a taste-masked formulation. However, the most appropriate in vivo method to assess the taste-masking efficacy of pediatric formulations remains unknown because it is not known to what extent the human taste panel/electronic tongue can predict the palatability in the pediatric patients. The purpose of this study was to develop taste-masked caffeine citrate extrudates via HME and to demonstrate the wide applicability of a single bottle-test rat model to record and compare the volume consumed of the taste-masked solutions to that of the pure API. Thus, this rat model can be considered as a low-cost alternative taste-assessment method to the most commonly used expensive human taste panel/electronic tongue method for pediatric formulations.     

枸橼酸咖啡因联合正压通气对新生儿呼吸窘迫患儿铁蛋白及Clara细胞分泌蛋白的影响

摘要 目的：探讨枸橼酸咖啡因联合正压通气对新生儿呼吸窘迫患儿铁蛋白及Clara细胞分泌蛋白的影响。方法：选取我院2016年1月到2021年1月共收治的82例新生儿呼吸窘迫患儿作为研究对象,所有患儿均需要机械通气治疗,将所有患儿随机分为观察组与对照组,每组41例。对照组患儿应用无创正压通气治疗,对照组患儿应用枸橼酸咖啡因联合无创正压通气治疗,对比两组患儿的住院时间、给氧时间和机械通气时间,治疗前后的呼吸功能指标与血气指标,治疗前后的SF、CC16表达水平以及两组患儿治疗过程中出现的用药不良反应和并发症情况。结果：观察组患儿的住院时间、给氧时间、机械通气时间明显低于对照组,组间对比,差异具有统计学意义（P＜0.05）;两组患儿治疗前P/F值、PaO₂、PaCO₂和pH值表达水平对比无明显差异（P＞0.05）,治疗24 h后,两组患儿pH值对比无明显差异（P＞0.05）,与对照组相比,观察组P/F值、PaO₂水平显著升高,PaCO₂水平显著降低（P＜0.05）;两组患儿治疗前SF、CC16水平对比无明显差异（P＞0.05）,治疗后两组患者SF、CC16表达水平均降低,且观察组显著低于对照组（P＞0.05）;观察组患儿并发症及不良反应发生总计11例,发生率为26.83,显著低于对照组的22例（53.66%）（P＜0.05）。结论：枸橼酸咖啡因联合正压通气比单一正压通气治疗新生儿呼吸窘迫效果更好,能够缩短患儿的住院时间和通气时间,减轻家属压力,同时能够提升患儿的氧合效率和血气指标,改善铁蛋白及Clara细胞分泌蛋白水平,降低并发症发生率,安全性好,值得临床应用推广。