Biorelevant in vitro assessment of dissolution and compatibility properties of a novel paediatric hydrocortisone drug product following exposure of the drug product to child-appropriate administration fluids

Wollmer, Erik; Neal, Greg; Whitaker, Martin J.; Margetson, Daniel N.; Klein, Sandra

doi:10.1016/j.ejpb.2018.10.022

Cited by 16 publications

(20 citation statements)

References 19 publications

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“…In a previous study in Europe, under the agreed EMA Paediatric Investigation Plan (PIP -EMEA 001283-PIP01-12) the compatibility of the hydrocortisone granules with artificial milk, whole milk and breast milk was assessed. Results from this study indicated that compared to administration with drinking water, in vivo hydrocortisone exposure in neonates, infants and pre-school children is unlikely to be affected by co-administration with milk and the composition of milk co-administered with the hydrocortisone granules (11). To ensure the safety and efficacy of the hydrocortisone granules after co-administration with soft food and drink matrices commonly used to assist in the administration of pediatric medicines, the FDA requested proof of compatibility with soft food matrices and administration fluids that are commonly used in the US.…”

Section: Introductionmentioning

confidence: 85%

“…In a previous study, typical dosing conditions, i.e. co-administration of the granules with water, breast milk and formula milk for children pre-weaning have been studied (11). This study focused on age-groups that are typically weaned, i.e.…”

Section: Age Groups To Be Addressedmentioning

confidence: 99%

“…Thus, non-pharmacopoeial test equipment would have been required for performing the experiments. However, since the objective was to run the experiments under standardized test conditions and to make the results comparable to those from the first part of the study (11), experiments were performed with the Mini-Paddle apparatus using a media volume of 200 or 195 ml, respectively. Where necessary, i.e.…”

Section: Dissolution and Solubility Studymentioning

confidence: 99%

“…Alternatively, they can be placed on a dry spoon and administered into the patient's mouth. Immediately after administration, the granules should be washed down with fluid, preferably drinking water, or for younger patients, breast or artificial milk (11). However, particularly when developing oral formulations for pediatric use, besides safety and efficacy, acceptability of the drug product is an important aspect to consider (13).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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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Section: Introductionmentioning

confidence: 85%

Section: Age Groups To Be Addressedmentioning

confidence: 99%

Section: Dissolution and Solubility Studymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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“…Pertama, dapat digunakan metode kristalisasi. Metode ini didasarkan pada perbedaaan daya kelarutan (126)(127)(128)(129)(130) antar zat yang dimurnikan dengan zat lain dalam suatu pelarut tertentu. Ada beberapa syarat suatu pelarut dapat dipakai dengan proses ekstraksi yaitu ada perbedaan kelarutan yang besar antara zat yang dimurnikan dengan zat pengotor, mudah di pisahkan dari kristal, dan tidak mudah bereaksi dengn kristal.…”

Section: Pendahuluanunclassified

Studi Termodinamika Transpor Ionik Natrium Klorida Dalam Air dan Campuran Tertentu

Hidayati¹,

Zainul²

2019

Preprint

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Natrium klorida dikenal dengan garam dapur. Senyawa ini memiliki rumus NaCl dan larut dalam air. Natrium klorida merupakan senyawa yang berwujud padat bentuk kristal dan berwarna putih. Natrium klorida merupakan senyawa ionik karena adanya ikatan antara logam natrium dengan non logam klorin. Natrium klorida, didalam air dapat terion menjadi ion ion penyusunnya. Penulisan review ini bertujuan untuk menganalisis interaksi molekul pada NaCl yang dilarutkan dalam air. Metode yang digunakan dalam menganalisis interaksi molekul adalah dengan permodelan menggunakan aplikasi ChemDraw 3D. Sedangkan untuk parameter mobilitas ion, konduktivitas, viskositas, dan konduktivitas molar digunakan perhitungan dan data dari salah satu jurnal yang telah di review. Penggunaan ChemDraw 3D dan ChemDraw 2D sebagai langkah untuk menganalisis atom atom penyusun NaCl beserta molekul dan pergerakan molekulnya. Hasil yang didapatkan yaitu struktur natrium klorida dengan analisis molekular 2D dan 3D. Analisis jari-jari natrium klorida pada Chemdraw 3D didapatkan sebesar 2,530A, dan jari jari atom natrium dan klor masing-masingnya sebesar 1.287A dan 1.688A. Setelah dilakukan optimasi MMFF94, didapatkan energi sterik sebesar 0.00073874 kcal/mol dan energi molekul bergerak dalam 30 interaksi atomnya adalah 101,4 kcal/mol. Natrium klorida mempunyai beberapa sifat termokimia dalam fasa padat pada tekanan 1 atm dan suhu 25°C ΔGf° 411.2, kj/mol, ΔHf° -384.1S° 72.1 dan C 50.5. Mobilitas ion natrium sebesar 5,19 m2s-1V-1 dan mobilitas ion klorin bernilai 7,91 m2s-1V-1.

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Vehicles for Drug Administration to Children: Results and Learnings from an In-Depth Screening of FDA-Recommended Liquids and Soft Foods for Product Quality Assessment

et al. 2022

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Purpose Mixing with liquids or soft foods is a common procedure to improve acceptability of oral medicines in children but may affect drug stability and the in vivo performance of the administered drug product. The aim of the present study was to obtain an overview of the variability of critical attributes of commonly used vehicles and to identify which vehicle characteristics need to be considered when developing in vitro methods for evaluating product quality. Methods One product of each vehicle listed in the FDA draft guidance “Use of Liquids and/or Soft Foods as Vehicles for Drug Administration” was analyzed with regard to composition, calorific content and physicochemical properties. Results The studied vehicles show wide variability, both in composition and physicochemical properties. No correlation was observed between vehicle composition and physicochemical properties. Comparison of results of the present study with previously published data also provided variability in physicochemical properties within individual vehicle types. Conclusions To identify acceptable (qualified) vehicles for global drug product labeling, it is important that the vehicles selected for in vitro compatibility screening reflect the variability in composition and essential physicochemical properties of the vehicles recommended on the product label, rather than relying on results obtained with a single vehicle of each type. Future activities will focus on the development of standardized dosing vehicles that can represent key vehicle characteristics in all their variability to ensure reliable risk assessment.

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Biorelevant in vitro assessment of dissolution and compatibility properties of a novel paediatric hydrocortisone drug product following exposure of the drug product to child-appropriate administration fluids

Cited by 16 publications

References 19 publications

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

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

Studi Termodinamika Transpor Ionik Natrium Klorida Dalam Air dan Campuran Tertentu

Vehicles for Drug Administration to Children: Results and Learnings from an In-Depth Screening of FDA-Recommended Liquids and Soft Foods for Product Quality Assessment

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