Evaluating Solubility of Celecoxib in Age-Appropriate Fasted- and Fed-State Gastric and Intestinal Biorelevant Media Representative of Adult and Pediatric Patients: Implications on Future Pediatric Biopharmaceutical Classification System.

Prediction of performance of traditional, reformulated, and novel oral formulations in adults and pediatrics is of great importance. This study was conducted to assess solubility of celecoxib in age-appropriate fasted- and fed-state gastric and intestinal biorelevant media, classify celecoxib into biopharmaceutical classification system (BCS), and assess the effects of age-related developmental changes in the composition and volume of gastrointestinal fluids on the solubility and performance of oral formulations containing celecoxib. Solubility of celecoxib was assessed at 37°C in the pH range specified by the BCS-based criteria in 13 age-appropriate biorelevant media reflective of the gastric and proximal small intestinal environment in both fasted and fed states in adults and different pediatric subpopulations. A validated HPLC-UV method was used to quantify celecoxib. Experimental and computational molecular descriptors and in vivo pharmacokinetic data were used to assign the permeability class of celecoxib. Celecoxib belonged to BCS class 2. The pediatric to adult solubility ratios were outside the 80-125% boundaries in 3 and borderline in 1 biorelevant media. Significant age-related variability could be predicted for oral formulations containing celecoxib intended for pediatric use. Findings of this study indicated that the criteria used in the adult BCS might not be directly applied to pediatric subpopulations.

Sub-chronic treatment with high doses of ascorbic acid reduces lead levels in hen eggs intentionally exposed to a concentrated source of lead: a pilot study.

BACKGROUND: Hen eggs contaminated with lead can be harmful to the health of children and adults. The objective of this pilot study was to investigate if sub-chronic treatment with ascorbic acid can reduce lead levels in the different parts of hen eggs after intentionally exposing the laying hens to a concentrated source of lead. METHODS: Clinically normal mixed-breed egg laying hens (n = 18) were used in this pilot study. Hens were exposed to a concentrated source of lead (200 mg/kgbody weight/day lead acetate) for 1 week. Subsequently, egg laying hens were either treated with sub-chronic doses of ascorbic acid (500 mg/kgbody weight/day) or left untreated for 4 weeks. Lead levels were assessed in egg-shell, egg-albumen, and egg-yolk samples using a graphite furnace atomic absorption spectrophotometer. RESULTS: Lead levels increased significantly (p-value < 0.01) from baseline in egg-yolk, egg-albumen, and egg-shell samples following 1 week exposure to lead acetate. Sub-chronic treatment of egg laying hens with high doses of ascorbic acid could bring statistically significant reduction (p-value < 0.01) in lead levels in egg-yolk, egg-albumen, and egg-shell samples after intentional exposure to a concentrated source of lead. CONCLUSIONS: Findings of this pilot study showed that sub-chronic treatment of egg laying hens with ascorbic acid can reduce lead levels in different egg parts after intentional exposure to a concentrated source of lead. Supplementing feedstuffs and water with sources of ascorbic acid could be beneficial in reducing lead levels in hen egg tissues following environmental exposure. Further studies are still required to investigate if ascorbic acid can reduce lead levels in other chicken tissues.