Mannitol-Coated Hydroxypropyl Methylcellulose as a Directly Compressible Controlled Release Excipient for Moisture-Sensitive Drugs: A Stability Perspective

Christina Yong Xin Kang; Keat Theng Chow; Yuan Siang Lui; Antoine Salome; Baptiste Boit; Philippe Lefevre; Tze Ning Hiew; Rajeev Gokhale; Paul Wan Sia Heng

doi:10.3390/ph17091167

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Mannitol-Coated Hydroxypropyl Methylcellulose as a Directly Compressible Controlled Release Excipient for Moisture-Sensitive Drugs: A Stability Perspective

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Mannitol-Coated Hydroxypropyl Methylcellulose as a Directly Compressible Controlled Release Excipient for Moisture-Sensitive Drugs: A Stability Perspective

Christina Yong Xin Kang, Keat Theng Chow, Yuan Siang Lui, Antoine Salome, Baptiste Boit, Philippe Lefevre, Tze Ning Hiew, Rajeev Gokhale and Paul Wan Sia Heng

Pharmaceuticals (Basel, Switzerland), Vol.17(9), 1167

09/04/2024

DOI: 10.3390/ph17091167

PMCID: PMC11435371

PMID: 39338330

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Abstract

Background/Objectives: Hydroxypropyl methylcellulose (HPMC) is one of the most commonly used hydrophilic polymers in formulations of matrix tablets for controlled release applications. However, HPMC attracts moisture and poses issues with drug stability in formulations containing moisture-sensitive drugs. Methods: Herein, the moisture sorption behavior of excipients and drug stability using aspirin as the model drug in matrix tablets were evaluated, using HPMC and the newly developed mannitol-coated HPMC, under accelerated stability conditions (40 °C, 75% relative humidity) with open and closed dishes. Results: Tablets prepared with mannitol-coated HPMC showed a slower drug degradation rate compared to tablets prepared with directly compressible HPMC. Initial moisture content and hygroscopicity were stronger predictors of drug stability compared to water activity when comparing samples without similar moisture content. In the early stage (day 0 to 30), the aspirin degradation rate was similar in both open and closed conditions, as moisture content is the main degradation contributor. In the later stage (day 30 to 90), aspirin degradation was faster under closed conditions than under open conditions, likely due to autocatalytic effects caused by the volatile acidic by-product entrapped in the closed environment. Conclusions: The findings from this study reinforced the importance of judicious excipient selection based on the understanding of excipient–moisture interactions to maximize the chemical stability of moisture-sensitive drugs. Mannitol-coated HPMC is a promising addition to the formulator’s toolbox for the formulation of controlled release dosage forms by direct compression.

hydroxypropyl methylcellulose

mannitol

co-processed

aspirin

stability

Details

Title: Subtitle: Mannitol-Coated Hydroxypropyl Methylcellulose as a Directly Compressible Controlled Release Excipient for Moisture-Sensitive Drugs: A Stability Perspective
Creators: Christina Yong Xin Kang - National University of Singapore
Keat Theng Chow
Yuan Siang Lui
Antoine Salome
Baptiste Boit - Roquette Frères (France)
Philippe Lefevre - Roquette Frères (France)
Tze Ning Hiew - National University of Singapore
Rajeev Gokhale
Paul Wan Sia Heng - Duke-NUS Medical School
Resource Type: Journal article
Publication Details: Pharmaceuticals (Basel, Switzerland), Vol.17(9), 1167
DOI: 10.3390/ph17091167
PMID: 39338330
PMCID: PMC11435371
NLM abbreviation: Pharmaceuticals (Basel)
ISSN: 1424-8247
eISSN: 1424-8247
Publisher: MDPI
Grant note: This research was funded by Roquette.
Language: English
Date published: 09/04/2024
Academic Unit: Pharmaceutical Sciences and Experimental Therapeutics
Record Identifier: 9984702834202771

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