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A Biopredictive In Vitro Approach for Assessing Compatibility of a Novel Pediatric Hydrocortisone Drug Product within Common Pediatric Dosing Vehicles.

ABSTRACT: 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. Graphical abstract.

SUBMITTER: Wollmer E

PROVIDER: S-EPMC7511475 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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A Biopredictive In Vitro Approach for Assessing Compatibility of a Novel Pediatric Hydrocortisone Drug Product within Common Pediatric Dosing Vehicles.

Wollmer Erik E Karkossa Frank F Freerks Lisa L Hetberg Anna-Elena AE Neal Greg G Porter John J Whitaker Martin J MJ Margetson Daniel D Klein Sandra S

Pharmaceutical research 20200924 10

<h4>Purpose</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 32968894

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Project description:BackgroundAmong the most common mucosal viral infections in infants are rotavirus, one of the main causes of severe gastroenteritis in infants and children up to 5 years, and respiratory syncytial virus (RSV), one of the leading causes of lower respiratory tract infections. Both human milk and bovine milk derived factors may provide protection against mucosal viral infections. More recently, a similar activity of milk derived proteins was suggested for SARS-CoV-2. The goal of the current study was to test antiviral activity of the bovine milkfat globule membrane (MFGM) against rotavirus, RSV and SARS-CoV-2 and to further characterize MFGM-enriched whey to identify which components in MFGM-enriched whey may contribute to the inhibitory activity.MethodsThe effects of MFGM-enriched whey, its whey protein isolate counterpart (WPI, obtained from the same production process) and a conventional whey protein concentrate (WPC) on rotavirus (strains Wa and SA114F), RSV (strain RSV-A2) and SARS-CoV-2 (Alpha variant) infectivity were determined using MA104 cells, human alveolar basal epithelial (A549) cells and monkey kidney (Vero E6) cells, respectively. The compounds were characterized in detail by LC-MS/MS and 31P-NMR to determine protein and phospholipid composition, respectively.ResultsRelative to its WPI counterpart, MFGM-enriched whey demonstrated a dose-dependent inhibition for both rotavirus and RSV whereas for SARS-CoV-2 inhibition was only observed at the highest concentration tested. Label-free quantification (LFQ) and intensity based absolute quantification (iBAQ) of identified proteins revealed a clear difference between MFGM-enriched whey and its controls including enrichment of known MFGM proteins and non-MFGM proteins that are enriched simultaneously, some of which have previously been demonstrated to display anti-viral activity. Although not completely absent from other whey protein preparations, MFGM-enriched whey had the highest specific and total phospholipid levels.ConclusionMFGM-enriched whey displayed antiviral activity against multiple viruses of clinical importance. This study provides insights into the active components in MFGM-enriched whey and may contribute to previous clinical observations with MFGM-enriched formula demonstrating reduced respiratory and gastrointestinal infections in formula fed infants.

Dataset Information

A Biopredictive In Vitro Approach for Assessing Compatibility of a Novel Pediatric Hydrocortisone Drug Product within Common Pediatric Dosing Vehicles.

Publications

A Biopredictive In Vitro Approach for Assessing Compatibility of a Novel Pediatric Hydrocortisone Drug Product within Common Pediatric Dosing Vehicles.

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