Curcumin amorphous solid dispersions formed by Eudragit EPO and hydroxypropyl methylcellulose E50 achieve superior analgesic effect

Abstract

Poor solubility of curcumin (Cur) has greatly limited its applications. To establish Cur amorphous solid dispersions (Cur ASDs) with superior analgesic effect, Eudragit EPO (EuD) and hydroxypropyl methylcellulose E50 (HPMC E50) were combined applied. Crystallization inhibition function of HPMC E50 in Cur ASDs was studied by analyzing the viscosity change and glass transition temperature (T_g). Critical micelle concentration and molar solubilization ratio of HPMC E50 were further studied. The hot plate analgesia and acetic acid writhing analgesia were conducted to confirm analgesic effects of Cur ASDs. The addition of HPMC E50 can reduce molecule motion and improve T_g of Cur ASDs, thus enhancing the stability of Cur ASDs. Cur@EuD/HPMC 3:1 with the best solubilization ability exhibited outstanding anti-oxidation ability and the best analgesic effects. The addition of HPMC E50 assisted analgesic effect, highlighting the special advantages of applying HPMC E50 for Cur ASDs formulated by EuD to improve analgesic effect.

Introduction

For most poorly water-soluble nutritions that belong to BCS II and BSC IV classes, the achievement of good bioavailability remains to be a long-sought goal [[1], [2], [3]]. As an effective strategy, amorphous solid dispersions (ASDs) that defined as the dispersion of drug within hydrophilic polymer carrier in an amorphous or molecular state of high energy can obviously increase the solubility and oral bioavailability of poorly water-soluble drug [[4], [5], [6]]. In the current stage, a large number of poorly water-soluble drugs with various medical treatment effects have been studied using ASDs [7,8]. Based on reports, different preparation methods (such as solvent evaporation, spray drying, hot melt extrusion, etc) can be applied to achieve ASDs with intended design for many poorly water-soluble drugs. The polymer used for establishing ASDs is not limited to single polymer, binary polymers or even multiple polymers can undertake the mission to be the excipient for ASDs [9]. The proper introduction of cellulose derivatives can effectively inhibit drug crystallization in ASDs. As hydroxypropyl methyl cellulose (HPMC) belongs to the nonionic surfactant, it is crucial to study its advantages in enhancing drug solubility.

As a popular nutrition component, Curcumin (Cur) belongs to a hydrophobic polyphenol derived from the rhizome of turmeric. Cur can exert functions of anti-oxidation, anti-cancer, and anti-inflammatory effects, etc. In addition, Cur can reduce the risk of kidney disease, cardiovascular disease and thyroid disease due to its excellent anti-oxidation properties [[10], [11], [12]]. It has been reported that Cur can prevent and treat acute kidney injury by modulating the molecular targets of several different cellular signaling pathways [13]. Cur has great value for the treatment and prevention of various diseases. Cur has a high oral safety dose [14,15], while the poor solubility and bioavailability strictly limited its usage [16]. To address this scientific problem, strategies such as micelle, ASDs [14], self-emulsifying and cyclodextrin complexation [17] have been applied. Representative polymers for designing ASDs consist of polyoxyethylene pyrrolidone, Eudragit, and polyethylene glycol [10,18]. As one type of Eudragit, Eudragit EPO (EuD) can be the main excipient for Cur ASDs [19,20], and can effectively enhance Cur solubility.

Pain, known as the fifth vital sign of the human body, is an important reminder of potential or existing damage. Long-term severe pain can seriously affect people’s quality of life. Therefore, the treatment and prevention of pain diseases are global hot topics. Since Cur is effective in treating and preventing pain diseases, our study focused on Cur ASDs to achieve superior analgesic effect. Herein, Cur ASDs were prepared by binary polymers of EuD and HPMC E50. The experiment of moisture uptake study was used to clarify the response of excipient to pH 1.0 hydrochloric acid. The addition of HPMC E50 in excipient was able to increase the viscosity of the system and improved the glass transition temperature (Tg) value of Cur ASDs, thus inhibiting crystallization and maintaining the stability of Cur ASDs. In vitro anti-oxidation assay was conducted to study the importance of HPMC E50 for Cur ASDs to achieve high anti-oxidation ability. Finally, analgesia tests that included the hot plate analgesia and acetic acid writhing analgesia studies were conducted to reveal the functions of HPMC E50 for Cur ASDs formulated by EuD in assisting analgesic effect.

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Materials

Cur (>99.0%) was purchased from meilunbio Co., Ltd. (China). EuD and HPMC E50 were kindly provided by Ashland (USA) and Anhui Shanhe Pharmaceutical Excipients Co., Ltd (China), respectively. Other agents were purchased from Tianjin Damao chemical reagent factory. All animal testing and procedures were approved by the Jinzhou Medical University Experimental animal Ethics Committee (241093).

Hainan Zhao, Xianbao Shi, Ermin Wang, Curcumin amorphous solid dispersions formed by Eudragit EPO and hydroxypropyl methylcellulose E50 achieve superior analgesic effect, Applied Materials Today, Volume 48, 2026, 103113, ISSN 2352-9407, https://doi.org/10.1016/j.apmt.2026.103113.

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