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Transport Properties of Ibuprofen Encapsulated in Cyclodextrin Nanosponge Hydrogels: A Proton HR-MAS NMR Spectroscopy Study
Published on: August 15, 2016
Model-Supported dissolution methods for Modified-Release Products: Enteric-coated versus extended-release ketoprofen
Mauricio A García1, Jozef Al-Gousous2, Pablo M González3
1Departamento de Farmacia, Escuela de Química y Farmacia, Facultad de Química y de Farmacia, Pontificia Universidad Católica de Chile, Santiago, 7820436, Chile.
International Journal of Pharmaceutics
|March 28, 2025
Summary
Dissolution testing for extended-release (XR) ketoprofen requires high buffer molarity for accurate in vitro-biopredictive results. Low molarity buffers do not fully capture the enhanced buffer capacity of XR dosage forms in vivo.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery Systems
- Physical Chemistry
Background:
- Drug product development faces challenges, with dissolution testing crucial for predicting in vivo performance.
- Poorly soluble ionizable drugs dissolve slower in biorelevant bicarbonate buffers due to a lowered effective pKa (pKa,eff).
- This effect may differ for controlled-release formulations like enteric-coated (EC) and extended-release (XR) dosage forms.
Purpose of the Study:
- To investigate and compare the in vitro dissolution profiles of enteric-coated (EC) and extended-release (XR) ketoprofen formulations.
- To assess the biorelevance of in vitro dissolution data obtained in low molarity buffers mimicking intestinal conditions.
- To elucidate the impact of formulation type and buffer conditions on drug dissolution and in vivo performance.
Main Methods:
- In vitro dissolution studies of EC and XR ketoprofen formulations in low molarity buffers.
- In vivo comparative bioavailability studies to confirm biorelevance.
- Mass/charge balance modeling to gain mechanistic insights into dissolution behavior.
Main Results:
- In vitro dissolution and in vivo absorption of EC tablets were influenced by coating polymer material.
- In vitro dissolution of XR formulations showed formulation-dependent discrepancies in low molarity media, which were not observed in vivo.
- Mechanistic modeling indicated that XR dosage forms exhibit enhanced buffer capacity in vivo due to slower diffusion and high liquid-to-solid ratios, which is not replicated by low molarity in vitro media.
Conclusions:
- Dissolution testing in low molarity buffers may not accurately predict the in vivo performance of XR ketoprofen formulations.
- Performing dissolution experiments at high buffer molarities is recommended to improve the biopredictivity of XR dosage forms.
- Understanding the interplay between formulation design, buffer conditions, and dissolution mechanisms is key for successful drug product development.
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