Heterogeneous hydroxypropylation for the preparation of hydroxypropyl carrageenan and its application in Plant-Based hard capsules

Plant-based hard capsules hold promise as medicinal excipients; however, the widely used gelling agent κ-carrageenan (κ-C) suffers from limitations such as poor aqueous solubility, and high dissolution temperature, which hinder the dissolution performance of the capsules. To overcome these drawbacks...

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Main Authors: Zi-Yun Zhou, Mi Zhang, Yu-Cheng Yang, Pei-Yong Liu, Yi Chen, Bing-De Zheng, Na Zhang, Xue-Qin Zhang, Jing Ye, Mei-Tian Xiao
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Carbohydrate Polymer Technologies and Applications
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666893925001306
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author Zi-Yun Zhou
Mi Zhang
Yu-Cheng Yang
Pei-Yong Liu
Yi Chen
Bing-De Zheng
Na Zhang
Xue-Qin Zhang
Jing Ye
Mei-Tian Xiao
author_facet Zi-Yun Zhou
Mi Zhang
Yu-Cheng Yang
Pei-Yong Liu
Yi Chen
Bing-De Zheng
Na Zhang
Xue-Qin Zhang
Jing Ye
Mei-Tian Xiao
author_sort Zi-Yun Zhou
collection DOAJ
description Plant-based hard capsules hold promise as medicinal excipients; however, the widely used gelling agent κ-carrageenan (κ-C) suffers from limitations such as poor aqueous solubility, and high dissolution temperature, which hinder the dissolution performance of the capsules. To overcome these drawbacks, we employed an industrially scalable heterogeneous hydroxypropylation method to modify κ-C. This process involves adjusting reaction parameters, including ethanol concentration, alkalization conditions and etherification conditions, to optimize the molar substitution degree (MS) and gel strength of the resulting hydroxypropylated carrageenan (HPC). Structural analysis using techniques such as FTIR spectroscopy, 1HNMR spectra and 13C NMR spectra confirmed the incorporation of hydroxypropyl groups into the κ-C backbone. Kinetic studies revealed that the hydroxypropylation reaction follows second-order kinetics with respect to propylene oxide, with an activation energy of 47.51 kJ/mol. Compared to κ-C, HPC exhibits improved water solubility, dissolving readily at lower temperatures, and demonstrates a lower gel-sol transition temperature, which facilitates easier processing. Tests show that capsules made from HPC exhibit a faster disintegration rate in pH 6.8 phosphate buffer compared to those made from κ-C and demonstrate an enhanced dissolution profile. These findings demonstrate a promising strategy to address the intrinsic limitations of κ-C and advance the development of plant-based hard capsules.
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spelling doaj-art-b6f7473f3ca74bf3abafc8036cbda5dd2025-08-20T02:39:35ZengElsevierCarbohydrate Polymer Technologies and Applications2666-89392025-06-011010079210.1016/j.carpta.2025.100792Heterogeneous hydroxypropylation for the preparation of hydroxypropyl carrageenan and its application in Plant-Based hard capsulesZi-Yun Zhou0Mi Zhang1Yu-Cheng Yang2Pei-Yong Liu3Yi Chen4Bing-De Zheng5Na Zhang6Xue-Qin Zhang7Jing Ye8Mei-Tian Xiao9College of Chemical Engineering, Huaqiao University, Xiamen, Fujian, 361021, PR China; Xiamen Engineering and Technological Research Center for Comprehensive Utilization of Marine Biological Resources, Xiamen, 361021, PR ChinaCollege of Chemical Engineering, Huaqiao University, Xiamen, Fujian, 361021, PR China; Xiamen Engineering and Technological Research Center for Comprehensive Utilization of Marine Biological Resources, Xiamen, 361021, PR ChinaCollege of Chemical Engineering, Huaqiao University, Xiamen, Fujian, 361021, PR China; Xiamen Engineering and Technological Research Center for Comprehensive Utilization of Marine Biological Resources, Xiamen, 361021, PR China; Corresponding authors.Jiangsu Lefan capsule ltd co., Zhengjiang, Jiangsu, 212028, PR ChinaGreenfresh (Fujian) Foodstuff Co., Ltd., Zhangzhou, Fujian, 363199, PR ChinaCollege of Chemical Engineering, Huaqiao University, Xiamen, Fujian, 361021, PR China; Xiamen Engineering and Technological Research Center for Comprehensive Utilization of Marine Biological Resources, Xiamen, 361021, PR ChinaCollege of Chemical Engineering, Huaqiao University, Xiamen, Fujian, 361021, PR China; Xiamen Engineering and Technological Research Center for Comprehensive Utilization of Marine Biological Resources, Xiamen, 361021, PR ChinaCollege of Chemical Engineering, Huaqiao University, Xiamen, Fujian, 361021, PR China; Xiamen Engineering and Technological Research Center for Comprehensive Utilization of Marine Biological Resources, Xiamen, 361021, PR ChinaCollege of Chemical Engineering, Huaqiao University, Xiamen, Fujian, 361021, PR China; Xiamen Engineering and Technological Research Center for Comprehensive Utilization of Marine Biological Resources, Xiamen, 361021, PR ChinaCollege of Chemical Engineering, Huaqiao University, Xiamen, Fujian, 361021, PR China; Xiamen Engineering and Technological Research Center for Comprehensive Utilization of Marine Biological Resources, Xiamen, 361021, PR China; Corresponding authors.Plant-based hard capsules hold promise as medicinal excipients; however, the widely used gelling agent κ-carrageenan (κ-C) suffers from limitations such as poor aqueous solubility, and high dissolution temperature, which hinder the dissolution performance of the capsules. To overcome these drawbacks, we employed an industrially scalable heterogeneous hydroxypropylation method to modify κ-C. This process involves adjusting reaction parameters, including ethanol concentration, alkalization conditions and etherification conditions, to optimize the molar substitution degree (MS) and gel strength of the resulting hydroxypropylated carrageenan (HPC). Structural analysis using techniques such as FTIR spectroscopy, 1HNMR spectra and 13C NMR spectra confirmed the incorporation of hydroxypropyl groups into the κ-C backbone. Kinetic studies revealed that the hydroxypropylation reaction follows second-order kinetics with respect to propylene oxide, with an activation energy of 47.51 kJ/mol. Compared to κ-C, HPC exhibits improved water solubility, dissolving readily at lower temperatures, and demonstrates a lower gel-sol transition temperature, which facilitates easier processing. Tests show that capsules made from HPC exhibit a faster disintegration rate in pH 6.8 phosphate buffer compared to those made from κ-C and demonstrate an enhanced dissolution profile. These findings demonstrate a promising strategy to address the intrinsic limitations of κ-C and advance the development of plant-based hard capsules.http://www.sciencedirect.com/science/article/pii/S2666893925001306Plant-based hard capsulesCarrageenanHydroxypropylationHeterogeneousSolubility
spellingShingle Zi-Yun Zhou
Mi Zhang
Yu-Cheng Yang
Pei-Yong Liu
Yi Chen
Bing-De Zheng
Na Zhang
Xue-Qin Zhang
Jing Ye
Mei-Tian Xiao
Heterogeneous hydroxypropylation for the preparation of hydroxypropyl carrageenan and its application in Plant-Based hard capsules
Carbohydrate Polymer Technologies and Applications
Plant-based hard capsules
Carrageenan
Hydroxypropylation
Heterogeneous
Solubility
title Heterogeneous hydroxypropylation for the preparation of hydroxypropyl carrageenan and its application in Plant-Based hard capsules
title_full Heterogeneous hydroxypropylation for the preparation of hydroxypropyl carrageenan and its application in Plant-Based hard capsules
title_fullStr Heterogeneous hydroxypropylation for the preparation of hydroxypropyl carrageenan and its application in Plant-Based hard capsules
title_full_unstemmed Heterogeneous hydroxypropylation for the preparation of hydroxypropyl carrageenan and its application in Plant-Based hard capsules
title_short Heterogeneous hydroxypropylation for the preparation of hydroxypropyl carrageenan and its application in Plant-Based hard capsules
title_sort heterogeneous hydroxypropylation for the preparation of hydroxypropyl carrageenan and its application in plant based hard capsules
topic Plant-based hard capsules
Carrageenan
Hydroxypropylation
Heterogeneous
Solubility
url http://www.sciencedirect.com/science/article/pii/S2666893925001306
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