Assessing solubility of meloxicam in age-specific gastric and intestinal media relevant to adults and pediatric populations: implications for optimizing dosing in patients for postoperative pain.

IF 2.8 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Sabreen Abu Omar, Rahma Nairat, Sara Khzimia, Iyad Maqboul, Mohammad Jaber, Ramzi Shawahna
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Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

评估美洛昔康在成人和儿童特定年龄段胃肠介质中的溶解度:对优化术后疼痛患者剂量的影响。
背景:口服制剂必须能溶于胃肠液才能被全身吸收。本研究测定了美洛昔康在 16 种不同年龄段的模拟胃肠介质中的溶解度,这些介质反映了儿科和成人的微环境:采用美国药典标准方法评估了美洛昔康在 16 种不同年龄段模拟胃肠生物相关介质中的溶解度。美洛昔康的分子描述符用于评估其肠道渗透性:结果:美洛昔康在特定年龄段的空腹和进食状态的模拟胃介质中,以及在儿科和成人中都表现出较低的溶解度。同样,美洛昔康在与喂食牛乳配方奶的新生儿相似的特定年龄模拟介质中也表现出较低的溶解度。另一方面,美洛昔康在模拟禁食和进食状态的其他特定年龄的小儿和成人肠道培养基中表现出较高的溶解度。在计算出的 12 个溶解度比中,有 7 个(58.3%)小儿与成人的溶解度比不在 80-125% 的范围内,有 1 个(8.3%)小儿与成人的溶解度比处于临界状态。这些结果表明,在 8 种(66.7%)对比介质中,美洛昔康的溶解度显示出显著的临床差异:结论:美洛昔康在成人和儿科特定年龄模拟胃介质中的溶解度较低,而在模拟肠介质中的溶解度较高。此外,小儿与成人的溶解度比可能具有重要的临床意义。这些差异可能导致含有美洛昔康的不同制剂更有可能无法证明其生物等效性,并导致这些制剂的性能出现差异。
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来源期刊
BMC Pharmacology & Toxicology
BMC Pharmacology & Toxicology PHARMACOLOGY & PHARMACYTOXICOLOGY&nb-TOXICOLOGY
CiteScore
4.80
自引率
0.00%
发文量
87
审稿时长
12 weeks
期刊介绍: BMC Pharmacology and Toxicology is an open access, peer-reviewed journal that considers articles on all aspects of chemically defined therapeutic and toxic agents. The journal welcomes submissions from all fields of experimental and clinical pharmacology including clinical trials and toxicology.
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