1. 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.
- Author
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Omar SA, Nairat R, Khzimia S, Maqboul I, Jaber M, and Shawahna R
- Subjects
- Humans, Adult, Child, Thiazoles pharmacokinetics, Thiazoles administration & dosage, Thiazoles chemistry, Intestinal Absorption, Thiazines pharmacokinetics, Thiazines administration & dosage, Thiazines chemistry, Age Factors, Intestinal Mucosa metabolism, Gastric Mucosa metabolism, Infant, Newborn, Child, Preschool, Meloxicam pharmacokinetics, Meloxicam chemistry, Meloxicam administration & dosage, Solubility, Anti-Inflammatory Agents, Non-Steroidal administration & dosage, Anti-Inflammatory Agents, Non-Steroidal pharmacokinetics, Anti-Inflammatory Agents, Non-Steroidal chemistry
- 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., (© 2024. The Author(s).)
- Published
- 2024
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