Department of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine.
An-Najah National University Hospital, Nablus, Palestine.
BMC Pharmacol Toxicol. 2024 Oct 9;25(1):75. doi: 10.1186/s40360-024-00799-7.
Oral dose formulations must be soluble in gastrointestinal fluids for systemic absorption. The solubility of meloxicam was determined in 16 different age-specific simulated gastric and intestinal media that mirrored the microenvironments in pediatrics and adults.
The solubility of meloxicam in the 16 different age-specific simulated gastric and intestinal biorelevant media was assessed using the standard US pharmacopeial method. The molecular descriptors of meloxicam were used to assess its intestinal permeability.
Meloxicam exhibited low solubility in the age-specific simulated gastric media for fasted and fed states and in pediatrics and adults. Similarly, meloxicam exhibited low solubility in the age-specific simulated media that mirrored neonates fed cow milk-based formula. On the other hand, meloxicam exhibited high solubility in the rest of the age-specific pediatric and adult intestinal media that simulated the fasted and fed states. The pediatric-to-adult solubility ratios were outside the 80-125% range in 7 (58.3%) and was borderline in 1 (8.3%) out of the 12 calculated ratios. These findings indicated that the solubility of meloxicam showed clinically significant differences in 8 (66.7%) of the compared media.
Meloxicam exhibited low solubility in the age-specific simulated gastric media and high solubility in the simulated intestinal media for adults and pediatrics. Moreover, the pediatric-to-adult solubility ratios may have clinically significant implications. These differences can be translated into a higher likelihood of failing to demonstrate bioequivalence of different formulations containing meloxicam and variabilities in the performance of these formulations.
口服剂型必须在胃肠道液中溶解才能被全身吸收。本研究旨在测定美洛昔康在儿科和成人不同年龄段模拟胃和肠生物相关介质中的溶解度。
采用美国药典标准方法测定美洛昔康在 16 种不同年龄段模拟胃和肠生物相关介质中的溶解度。利用美洛昔康的分子描述符评估其肠道通透性。
美洛昔康在禁食和进食状态下以及儿科和成人的特定年龄段模拟胃液中的溶解度均较低。同样，美洛昔康在模拟新生儿食用基于牛乳配方的特定年龄段模拟介质中的溶解度也较低。另一方面，美洛昔康在其余模拟禁食和进食状态的儿科和成人特定年龄段的模拟肠介质中具有较高的溶解度。在计算的 12 个比值中，有 7 个（58.3%）比值超出 80-125%的范围，有 1 个（8.3%）比值接近该范围。这些发现表明，在 8 种（66.7%）比较介质中美洛昔康的溶解度存在临床显著差异。
美洛昔康在特定年龄段的模拟胃液中的溶解度较低，在成人和儿科的模拟肠介质中的溶解度较高。此外，儿科到成人的溶解度比值可能具有临床意义。这些差异可能导致含有美洛昔康的不同制剂生物等效性失败的可能性增加，以及这些制剂性能的变异性。
