RUSSIAN JOURNAL OF GENERAL CHEMISTRY
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2024
·Vol. 94
·期 1
·170-183
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IF 0.9
Li T.,Fu X.,Wang Y.,Ouyang F.,Liu L.,Wen M.,Zha G.,Zhu L.
Abstract Celecoxib (CXB) is a nonsteroidal anti-inflammatory drug (NSAID). However, the application of CXB has been compromised by its poor aqueous solubility and low oral bioavailability. We developed a series of ternary solid dispersions (SDs) of CXB to increase its solubility. In this study, the polymers were screened to determine that they have the potential to increase the solubility of CXB in the solution. A hydrophilic polymer-hydroxypropyl methylcellulose (HPMC) and a surfactant Tween80 were employed as matrix respectively in the optimized formulations. Experimental data revealed that CXB was molecularly distributed within all dispersions in amorphous form by using Differential Scanning Calorimetry (DSC), Polarizing Light Microscopy (PLM), and X-ray powder diffraction (XRD). Fourier Transform Infrared Spectroscopy (FTIR) results showed that the characteristic peaks of CXB have shifted. Compared with pure CXB, the addition of excipients can reduce the contact angle, and improve the solubility of CXB. Ternary SDs were dissolved in PBS (pH 6.8) and formed drug-carrying nanoparticles. In vitro dissolution results indicated that the dissolution amount of HPMC-CXB 5 : 1 SD (32.08±1.56% for 120 min) was higher than pure CXB (3.09±0.29%). In particular, the greatest dissolution enhancement was obtained from the test of which the result was HPMC/Tween80-CXB 3 : 2 : 1 SD (44.12±2.01% for 120 min). This study showed that ternary SDs could be a promising strategy for improving CXB dissolution.
研究领域:
药剂学
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药物化学
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DOI
高影响因子
FLAVOUR AND FRAGRANCE JOURNAL
·
2016
·Vol. 32
·期 2
·102-111
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IF 1.693
Zujin Yang,Liyun Huang,Xingdong Yao,Hongbing Ji
Estragole (ES) has multiple biological activities and is widely used in food preservation. However, the applications of ES are limited because of its low water solubility and high volatility nature. In this paper, the β-cyclodextrin (β-CD) inclusion complex of ES was prepared by a co-precipitation method with the aim of enhancing its thermal stability and realize its controlled release. Solubility experiments were performed to evaluate the effect of β-CD on ES aqueous solubility. Release experiments of ES from its inclusion complexes were carried out at different temperatures with a relative humidity (RH) and Avrami's equation was used to analyse the release data. The antimicrobial activity of the free and included ES was also examined. The results indicated that the host–guest interactions played a crucial role in enhancing the properties of ES. The inclusion complex was investigated using physico-chemical techniques such as Fourier transform infrared spectroscopy (FTIR), thermal analysis (TGA and DSC), 1H and 2D nuclear magnetic resonance (NMR). The inclusion processes between β-CD and ES were simulated using the semi-empirical PM3 and ONIOM [B3LYP/6-31g(d):PM3] methods. Copyright © 2016 John Wiley & Sons, Ltd.
研究领域:
食品科学
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药物化学
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分子生物学
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DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2022
·
IF 5.062
Guan-Lan Huang,Ling Yang,Bo-Ying Ren,Xin-Yue Lv,Ling-Yi Song,Xia-Lin Dai,Jia-Mei Chen
Vemurafenib (VEM) is a first-line drug for the treatment of metastatic melanoma with BRAF V600 mutation, which was developed in the form of amorphous solid dispersion to overcome the defects of poor aqueous solubility and oral absorption. However, the oral dose of VEM is still very high; besides, the poor stability of amorphous form may increase the risks in drug effectiveness and safety. Herein, we attempted to provide a solution to these issues based on cocrystallization strategy. Three cocrystalline forms involving VEM and D / L / dl -camphorsulfonic acid with stoichiometric ratio of 1:1 were synthesized and characterized by powder X-ray diffraction analysis, 1 H nuclear magnetic resonance, thermal analyses and Fourier transform infrared spectroscopy . The in vitro evaluations show that all of the cocrystalline forms demonstrate improved hygroscopicity and stability compared to amorphous VEM; especially, the cocrystalline form with dl -camphorsulfonic acid exhibits much better tabletability and apparent solubility than all of other forms. Pharmacokinetic tests reveal that all the cocrystallized products show significantly enhanced C max and AUC 0-t values compared to the amorphous form. Therefore, the newly discovered cocrystalline forms of VEM are expected to overcome the issues of poor solubility and oral absorption and provide great potential for the development of improved preparations of the drug.
研究领域:
药物化学
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药剂学
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肿瘤学
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DOI
高影响因子
DALTON TRANSACTIONS
·
2023
·Vol. 52
·期 36
·12909-12917
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IF 4
Xiao-Hui Dong,Zhi-Gang Li,Dong-Yan Bian,Tian-Meng Guo,Zi-Ying Li,Wei Li,Hongpeng He
Metal–organic frameworks (MOFs) have shown significant potential for drug delivery applications. However, there remains a scarcity of comprehensive research addressing the influence of surface properties of MOFs on drug release kinetics and drug solubility. This study focuses on examining the influence of MOFs hydrophilicity and hydrophobicity on the controlled release and solubility of drugs. To achieve this, we prepared drug-loaded nanoparticles through in situ synthesis and created a drug-MOF co-amorphous system using the ball milling technique. Under neutral conditions, the hydrophilic MOF-based drug delivery system demonstrated a comparatively slower drug release profile than its hydrophobic counterpart. This observation suggests that the hydrophilic system holds promise in mitigating drug side effects by enabling improved control over drug release. The implementation of hydrophobic MOFs in co-amorphous systems yields a more pronounced effect on enhancing solubility compared to hydrophilic MOFs. This study offers valuable insights for achieving optimal drug release kinetics and solubility by delicately manipulating surface properties of MOFs.
研究领域:
药剂学
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材料科学
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DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2024
·
IF 4.5
Xuehan Wang,Juan Xu,Ting Wang
At present, contraceptive drugs such as Drospirenone (DROP) encounter challenges stemming from their abbreviated half-life and constrained efficacy. Therefore, the imperative arises to formulate innovative strategies that not only prolong the duration of action but also enhance the overall effectiveness of these drugs. This study introduces a two-step delivery system designed to overcome the limitations associated with DROP applications. Initially, a Drospirenone liposome (LIP/DROP) complex was meticulously prepared. Subsequently, this complex was immobilized within a cellulose-based hydrogel, constructed from aldehyde-replaced oxidized regenerated cellulose (AC) and chitosan (CS), employing Schiff base reaction crosslinking. The encapsulation efficiency achieved an impressive 84.9% (±0.73), accompanied by an 878-fold increase in solubility. Notably, each 0.35 g of the hydrogel demonstrated the capacity to load 96.48 mg of DROP. TEM was used to observe the particle size and morphology of LIP/DROP. SEM and FTIR were employed to investigate the structure and surface morphology of the prepared hydrogel and AC. The properties of the hydrogel related to the application of drug delivery, including swelling, mechanical, bacterial inhibition, and cytotoxicity were meticulously investigated. Moreover, the drug release rate of the prepared LIP hydrogel was assessed over 400 h (9%–40%), demonstrating its potential for sustained release of DROP. These improvements in solubility and stability offer promise for expanding the utilization of DROP in contraceptive applications.
研究领域:
药剂学
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材料科学
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药物递送
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产品关联
DOI
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2019
·
IF 2.367
Yu-Jiao Xie,Qi-Long Wang,Michael Adu-Frimpong,Jian Liu,Kang-Yi Zhang,Xi-Ming Xu,Jiang-Nan Yu
Isoliquiritigenin (ISL) possesses a variety of pharmacological activities amid poor solubility in water which has restricted its clinical application. In this study, isoliquiritigenin-loaded F127/P123 polymeric micelles (ISL-FPM) were successfully prepared and evaluated in vitro and in vivo. The particle size, polydispersity index, and zeta potential of the selected formulation were 20.12 ± 0.72 nm, 0.183 ± 0.046, and −38.31 ± 0.33 mV, respectively, coupled with high encapsulation efficiency of 93.76 ± 0.31%. Drug-loading test showed the solubility of ISL after formulating into micelles was 232 times higher than its intrinsic solubility. Moreover, critical micelle concentration (CMC) was tested with fluorescence probe method and turned out to be quite low, which implied high stability of ISL-FPM. Release profile in HCl (pH 1.2), double distilled water, and PBS (pH 7.4) of ISL-FPM reached over 80%, while free ISL was around 40%. Pharmacokinetic research revealed that formulated ISL-FPM significantly increased bioavailability by nearly 2.23-fold compared to free ISL. According to the results of in vitro antioxidant activity, scavenging DPPH activity of ISL was significantly strengthened when it was loaded into polymeric micelles. Altogether, ISL-FPM can act as a promising approach to improve solubility as well as enhance bioavailability and antioxidant activity of ISL.
研究领域:
药剂学
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药物化学
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DOI
PubMed
高影响因子
JOURNAL OF INCLUSION PHENOMENA AND MACROCYCLIC CHEMISTRY
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2019
·Vol. 94
·期 1
·85-94
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IF 1.429
Li Shuhan,Tang Yue,Zhang Xinru,Dou Yushun,Shen Xiangchun
This research is to study on preparation and characterization of diclofenac sodium β-cyclodextrin (DS-β-CD) inclusion complex eye drops in order to improve the solubility of diclofenac sodium (DS) and reduce the irritation of DS eye drops in the market. First, DS-β-CD inclusion complex was prepared by co-precipitation method and then mixed with excipients to prepare inclusion complex eye drops. Finally, instruments were used to determine the basic properties of eye drops and animal experiments were used to investigate the irritation of the DS-β-CD inclusion complex eye drops. The drug content, the encapsulation efficiency and the yield of DS-β-CD inclusion complex were respectively 17.11, 84.20 and 60.00%. And the DS-β-CD inclusion complex was identified by FTIR, DSC, XRD and 1 HNMR. The solubility of the inclusion complex was 20 times more than DS. The pH value, the osmotic pressure, the viscosity and the drug content of the eye drops were respectively 7.20, 298 mosmol/kg, 4.88 mPa s and 97.98%. In brief, DS-β-CD inclusion complex eye drops had stable properties, high solubility and the test items met the requirements. The eye drops were almost non-irritating, significantly reducing the irritation of the original prescription (P < 0.01).
研究领域:
药剂学
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药物化学
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产品关联
DOI
高影响因子
POULTRY SCIENCE
·
2024
·
IF 3.8
Jianting Gao,Yingsai Fan,Chenyue Lu,Xinghua Zhao,Xin He
ABSTRACT Baicalein ( BAI ) is a natural flavonoid with antioxidant, antitumor and antibacterial properties. However, the bioavailability of BAI was limited due to low solubility. This study aims to improve the solubility of BAI through the amorphous solid dispersion ( ASD ) and evaluate changes in its pharmacokinetics and pharmacodynamics in Taihang chickens. Polyethylene caprolactam-polyvinyl acetate-polyethylene glycol grafted copolymer ( Soluplus ) was chosen as the carrier, and ASD was prepared by rotary evaporation and was characterized by powder X-ray diffractions ( PXRD ), differential scanning calorimetry (DSC ) and fourier transform infrared spectroscopy (FT-IR ). In vitro dissolution assays were used to screen the optimal ratio of drug to carrier, in vivo pharmacokinetic assays were conducted to investigate the promoting effect on the absorption. In addition, the effects of ASD on the growth performance, meat quality, antioxidant capacity and intestinal flora were investigated. ASD (1:9 and 2:8) did not exhibit crystal diffraction peaks of BAI in PXRD or endothermic peaks in DSC, indicating the successful preparation of ASD. The results of in vitro dissolution assay showed that the cumulative dissolution rate of ASD (2:8) within 600 min was 52.67%, which was 7.84-fold higher than BAI. The pharmacokinetic results showed that the peak concentration ( C max ) and the area under the drug-time curve ( AUC 0∼24 ) of ASD (2:8) was (5.20 ± 0.82) μg/mL and (17.03 ± 0.67) μg·h/mL, which was 1.91 and 2.64-fold higher than BAI, respectively. Dietary supplementation of BAI and ASD could increase average daily gain ( ADG ), while decrease feed conversion ratio ( FCR ), but there was no significant difference ( P > 0.05). The drip loss of BAIASD group was lower than BAI group ( P < 0.05). In addition, the antioxidant capacity of Taihang chickens were enhanced, the diversity and the abundance of beneficial bacteria was improved. Results of BAI upon the dietary supplementation tested in Taihang chickens, after preparation of ASD, indicating a superior enhancement effect in growth performance, meat quality, antioxidant capacity and intestinal flora due to an improved solubility and optimized bioavailability.
研究领域:
药理学
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动物营养学
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食品科学
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产品关联
DOI
PubMed
高影响因子
Journal of Pharmaceutical Innovation
·
2025
·Vol. 20
·期 2
·1-10
·
IF 2.7
Liu Jie,Liu Qingyue,Zhang Zhi,Yang Wenzhi,Li Haiying
Purpose Bezafibrate (BZF), a fibrates lipid-lowering drug, is primarily used in clinical practice for hyperlipidemia with significantly elevated triglycerides (TG). Its effect on reducing TG is more pronounced than that of statins, compensating for the shortcomings of statin medications. However, BZF is a BCS class II drug due to its low solubility in water and its poor oral bioavailability. To enhance the solubility and bioavailability of BZF, a co-amorphous complex comprising BZF and a hydrotrope was prepared. Methods Arginine (Arg) was selected as a hydrotrope for BZF. The BZF-Arg co-amorphous complex was prepared by the freeze-drying method and characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC). Moreover, the complex was evaluated by stability test, in vitro release experiment and pharmacokinetic study. Results The characterization results demonstrated that the formation of hydrogen bonds between BZF and Arg, and the crystalline state of the drug was transformed into the amorphous state in the BZF-Arg complex. Moreover, the complex exhibited good stability and better release in vitro. The pharmacokinetic study revealed that the peak concentration (C max ) and the area under the curve (AUC 0→36 ) of the BZF-Arg complex were significantly improved compared to those of the BZF suspension, following the relative bioavailability of 255%. Conclusion BZF-Arg co-amorphous complex prepared by the combination of hydrotropy and solid dispersion technique provides a promising strategy for enhancing the solubility and bioavailability of BZF. Graphical
研究领域:
药剂学
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药物化学
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DOI
高影响因子
SAUDI PHARMACEUTICAL JOURNAL
·
2019
·
IF 3.643
Hao Liu,Wenmei Zhao,Qi Hu,Ling Zhao,Yumeng Wei,Chao Pi,Yuhan Yang,Xuerong Yang,Hang Yuan,Yuhan Zhang,Kunyan Qu,Xinyu Shi,Yao Huang,Houyin Shi
Dihydromyricetin (DHM) is a natural dihydroflavonol compound with quite a number of important pharmacological properties. However, its low solubility in water and poor stability in aqueous environment, have compromised drug efficacy of DHM, thus hindering its clinical use. The present study was to develop DHM-loaded gastric floating sustained-release tablet (DHM-GFT) to improve the bioavailability of DHM. DHM-GFT was prepared via powder direct compression. The formulation of tablet was optimized in terms of the floating ability and drug release rate. The optimized DHM-GFT exhibited short floating lag time of less than 10 s and long floating duration of over 12 h in acidic medium. It had a 12-hour sustained release of DHM, which proved its potential to develop as a twice-a-day dosing preparation. The physicochemical properties of DHM-GFT well satisfied the pharmacopoeial requirements. In addition, the results from pharmacokinetic studies demonstrated that, DHM-GFT could considerably prolong the in vivo residence time of drug and improve the bioavailability via good gastric floating ability and sustained drug release when compared to DHM powder. Therefore, DHM-GFT is promising to promote the application of DHM and merits studies for further development.
研究领域:
药剂学
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药物开发
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药代动力学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2019
·
IF 4.213
Jian Liu,Qilong Wang,Michael Adu-Frimpong,Qiuyu Wei,Yujiao Xie,Kangyi Zhang,Chunmei Wei,Wen Weng,Hao Ji,Elmurat Toreniyazov,Ximing Xu,Jiangnan Yu
Isoliquiritigenin (ISL) has a great variety of pharmacological effects especially liver cancer therapy, but its poor solubility, bioavailability and liver targeting have limited its clinical use. In order to solve the aforementioned shortcomings, the TPGS-modified proliposomes loaded with ISL (ISL-TPGS-PLP) was prepared in this study. ISL-TPGS-PLP was fabricated via thin-film dispersion method and was characterized by the appearance, particle size, zeta potential and morphology. HPLC was used to evaluate entrapment efficiency (EE), in vitro release and stability of ISL-TPGS-PLP single or combined while appropriate physicochemical parameters were measured with DLS . Meanwhile, the pharmacokinetics and tissue distribution were also studied after oral administration. The results demonstrated that ISL-TPGS-PLP had a mean size of 23.8 ± 0.9 nm , high EE of 97.33 ± 0.40%. More importantly, nearly 90% ISL was released from ISL-TPGS-PLP within 24 h while only 50% was released from ISL suspension. In the pharmacokinetics study, the area under the curve (AUC 0-24h) of ISL-TPGS-PLP was 1.53 times higher than that of ISL suspension. The Tissue distribution study showed that the ISL released from ISL-TPGS-PLP was higher in the liver than the free ISL suspension. Altogether, ISL-TPGS-PLP could ameliorate the ISL solubility, bioavailability and liver targeting ability, suggesting that ISL-TPGS-PLP could serve as a promising nanocarrier for liver cancer therapy.
研究领域:
药剂学
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肿瘤学
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DOI
PubMed
高影响因子
Artificial Cells Nanomedicine and Biotechnology
·
2018
·
IF 3.026
Pinggang Ding,Hongxue Shen,Jianan Wang,Jianming Ju
The aim of this study was to prepare two novel magnolol (MO)-loaded binary mixed micelles (MO-M) using biocompatible copolymers of Soluplus (SOL) and Solutol® HS15 (HS15), SOL and d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS), to improve magnolol’s poor solubility and its oral bioavailability. The organic solvent evaporation method was used to obtain two MO-M by optimization; one was prepared by using SOL and HS15 (MO-H), and the other was prepared by using SOL and TPGS (MO-T). The entrapment efficiency (EE%) and drug loading (DL%) of MO-T were 94.61 ± 0.91% and 4.03 ± 0.19%, respectively, and the MO-H has higher EE% and DL% (98.37 ± 1.23%, 4.12 ± 0.16%). TEM results showed that the morphology of MO-M was homogeneous and was spherical in shape. The dilution stability of MO-M did not undergo significant changes. Permeability of MO-M across a Caco-2 cell monolayer was enhanced in Caco-2 cell transport models. The pharmacokinetics study showed that the relative oral bioavailability of MO-T and MO-H increased by 2.39- and 2.98-fold, respectively, compared to that of raw MO. This indicated that MO-H and MO-T could promote absorption of MO in the gastrointestinal tract. Collectively, the mixed micelles demonstrated greater efficacy as a drug delivery system. The development of these novel mixed micelles is valuable for resolving the poor solubility and bioavailability of drugs.
研究领域:
药剂学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）