A Biopredictive In Vitro Approach for Assessing Compatibility of a Novel Pediatric Hydrocortisone Drug Product within Common Pediatric Dosing Vehicles
Open accessAbstract
Purpose: The objective of the present work was to screen whether a novel pediatric hydrocortisone granule formulation can be co-administered with common food matrices and liquids. Methods: Pediatric hydrocortisone granules were studied using a biopredictive in vitro approach. Experiments included an in situ chemical compatibility study of active ingredient and drug product with liquid dosing vehicles and soft foods commonly ingested by infants, pre-school- and school children. Drug solubility and stability experiments in the different vehicle types and, drug release/dissolution experiments mimicking age-related pediatric gastric conditions after administering the hydrocortisone granules together with the dosing vehicles and after different exposure/mixing times were performed. Results: In the simulated dosing scenarios applied in dissolution experiments, in vitro dissolution in gastric conditions was rapid and complete. Results of the chemical compatibility/stability studies indicated that mixing with the different dosing vehicles studied should not be an issue regarding drug degradation products. Conclusions: A novel in vitro approach ensuring a proper risk assessment of the use of dosing vehicles in the administration of pediatric dosage forms was established and applied to a novel pediatric hydrocortisone drug product. The studied dosing vehicles were shown to not alter performance of the drug product and are thus considered suitable for administration with hydrocortisone granules.
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The increased absorption delay at higher hydrocortisone doses can be explained by the low aqueous solubility of hydrocortisone (0.35-0.40 mg/mL).
“The increased absorption delay at higher doses can be explained by the low aqueous solubility of hydrocortisone (0.35–0.40 mg/mL) [29].”
From A quantitative modeling framework to understand the physiology of the hypothalamic-pituitary-adrenal axis and interaction with cortisol replacement therapy (2024) · cites this paper as [29]
The Introduction (page unavailable) reports aqueous solubility of 0.35–0.40 mg/mL, supporting the quoted value. It does not attribute increased absorption delay at higher doses to that solubility; instead, the Introduction and Results and Discussion say solubility should not be an issue across the pediatric doses studied. (LLM, conf=0.88)
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Bindellini, D., Michelet, R., Aulin, L. B. S., Melin, J., Neumann, U., Blankenstein, O., Huisinga, W., Whitaker, M. J., Ross, R., & Kloft, C. (2024) · Journal of Pharmacokinetics and Pharmacodynamics · doi:10.1007/s10928-024-09934-7 · Cited by 4 · see citing works
“The increased absorption delay at higher doses can be explained by the low aqueous solubility of hydrocortisone (0.35–0.40 mg/mL) [ 29].”
InfluentialSelf-citation
- Authors
- Wollmer, E., Karkossa, F., Freerks, L., Hetberg, A.-E., Neal, G., Porter, J., Whitaker, M. J., Margetson, D., & Klein, S.
- Affiliations
- Universität Greifswald (DE)
- Diurnal (United Kingdom) (GB)
- Corresponding author
- Klein, Sandra
- Venue
- Pharmaceutical Research
- Published
- 2020-09-24
- Volume
- 37
- Issue
- 10
- Pages
- 203-203
- ISSN
- 0724-8741 (ISSN-L)
- 1573-904X
- PMC
- PMC7511475
- OpenAlex
- W3088441571
- Cited by
- 30
- References
- 22
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 5 · 2023: 2 · 2022: 3 · 2021: 11
- FWCI
- 3.83
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Pharmaceutical Research (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by)
- Funders
- Universität Greifswald
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Physical Sciences › Chemistry › Analytical Chemistry › Analytical Methods in Pharmaceuticals
- Keywords
- cortisol, food compatibility, chemical compatibility, drug stability, drug solubility, in vitro dissolution, gastric diseases, pediatric formulations, drug release
- MeSH terms
- Administration, Oral, Child, Child, Preschool, Drug Compounding, Drug Stability, Pharmaceutical Preparations, Food, Humans, Hydrocortisone, Infant, Pediatrics, Solubility, Food-Drug Interactions, Drug Liberation, In Vitro Techniques
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