JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2018
·
IF 2.297
Wenhao Xu,Ying Sun,Liping Du,Yulia S. Chistyachenko,Alexandr V. Dushkin,Weike Su
Valsartan has been used for the treatment of hypertension disease. However, the oral bioavailability of valsartan has been reported to be only ∼23%, accompanied with high permeability and poor aqueous solubility. The object of this research was to prepare solid dispersions of valsartan with an inorganic (CaCO 3 ) and organic base ( N -methyl- d -glucamine) in an effort to increase the aqueous solubility and dissolution rate of the drug. The as-prepared solid dispersions of valsartan were prepared in an environmentally friendly manner using CaCO 3 and MG and a roll mill. The physicochemical properties were studied in the solid state using DSC , PXRD and IR. Furthermore, the solubility of valsartan increased 46-fold in solid dispersion with CaCO 3 and 9-fold in solid dispersion with MG. More than 95% of valsartan in solid dispersions was found to be released in simulated intestinal fluid, whereas only 35% was found to be released using pure valsartan within the same time interval. Storage tests showed that the as-prepared solid dispersions were equally stable compared to pure valsartan at 40 °C. Potentially, the synthesized solid dispersions of valsartan with enhanced solubility and dissolution rates may represent promising formulations for improving the overall oral bioavailability of the drug in clinical applications.
研究领域:
药剂学
·
药物化学
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DOI
高影响因子
Pharmaceutics
·
2021
·Vol. 14
·期 1
·23
·
IF 6.321
Chenxin Duan,Wenwen Liu,Yunwen Tao,Feifei Liang,Yanming Chen,Xinyi Xiao,Guisen Zhang,Yin Chen,Chao Hao
Palbociclib (PAL) is an effective anti-breast cancer drug, but its use has been partly restricted due to poor bioavailability (resulting from extremely low water solubility) and serious adverse reactions. In this study, two cocrystals of PAL with resorcinol (RES) or orcinol (ORC) were prepared by evaporation crystallization to enhance their solubility. The cocrystals were characterized by single crystal X-ray diffraction, Hirshfeld surface analysis, powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, Fourier transform infrared and scanning electron microscopy. The intrinsic dissolution rates of the PAL cocrystals were determined in three different dissolution media (pH 1.0, pH 4.5 and pH 6.8), and both cocrystals showed improved dissolution rates at pH 1.0 and pH 6.8 in comparison to the parent drug. In addition, the cocrystals increased the solubility of PAL at pH 6.8 by 2–3 times and showed good stabilities in both the accelerated stability testing and stress testing. The PAL-RES cocrystal also exhibited an improved relative bioavailability (1.24 times) than PAL in vivo pharmacokinetics in rats. Moreover, the in vitro cytotoxicity assay of PAL-RES showed an increased IC50value for normal cells, suggesting a better biosafety profile than PAL. Co-crystallization may represent a promising strategy for improving the physicochemical properties of PAL with better pharmacokinetics.Keywords:palbociclib;cocrystal;Hirshfeld surface;solubility;dissolution rate;physical stability
研究领域:
药学
·
化学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
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2017
·
IF 3.756
Yu Huang,Jin-Mei Li,Zhi-Hui Lai,Jun Wu,Tong-Bu Lu,Jia-Mei Chen
Both cocrystal and nanocrystal technologies have been widely used in the pharmaceutical development for poorly soluble drugs. However, the synergistic effects due to the integration of these two technologies have not been well investigated. The aim of this study is to develop a nano-sized cocrystal of phenazopyridine (PAP) with phthalimide (PI) to enhance the release rate and oral bioavailability of PAP. A PAP–PI nano-cocrystal with particle diameter of 21.4 ± 0.1 nm was successfully prepared via a sonochemical approach and characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and dynamic light scattering (DLS) analysis. An in vitro release study revealed a significant release rate enhancement for PAP–PI nano-cocrystal as compared to PAP–PI cocrystal and PAP hydrochloride salt. Further, a comparative oral bioavailability study in rats indicated significant improvement in C max and oral bioavailability (AUC 0 − ∞ ) by 1.39- and 2.44-fold, respectively. This study demonstrated that this novel nano-cocrystal technology can be a new promising option to improve release rate and absorption of poorly soluble compounds in the pharmaceutical industry.
研究领域:
药剂学
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药物递送
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纳米医学
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药物代谢
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晶体工程
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2021
·Vol. 22
·期 2
·928
·
IF 5.924
Muhammad Inam,Lu Liu,Jian-Wei Wang,Ka-Xi Yu,Chi-Uyen Phan,Jie Shen,Wen-Hua Zhang,Guping Tang,Xiurong Hu
Puerarin (PUE) is a Chinese traditional medicine known to enhance glucose uptake into the insulin cells to downregulate the blood glucose levels in the treatment of type II diabetes. Nevertheless, the bioavailability of pristine PUE is limited due to its poor solubility and low intestinal permeability. In this work, we demonstrate that the solubility of PUE can be significantly enhanced via its co-crystallization with L-Proline (PRO). Two crystalline phases, namely, the solvate-free form [PUE][PRO] (I) and the solvated form [PUE]2[PRO]∙EtOH∙(H2O)2(II) are isolated. These two phases are characterized by single-crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), Fourier-transformed infrared (FT-IR) spectra, nuclear magnetic resonance (NMR), and thermogravimetric analysis in association with differential scanning calorimetry (TGA-DSC). The solubility and dissolution rate of bothIandIIin water, gastrointestinal tract at pH 1.2, and phosphate buffer at pH 6.8 indicates a nearly doubled increase as compared to the pristine PUE. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay of pristine PUE,IandIIagainst murine colon cancer cell lines CT-26 and human kidney cell lines HEK-293 indicated that neither compound exhibits obvious cytotoxicity after 24 h. This work showcases that the readily available and biocompatible PRO can be a promising adjuvant to enhance the physicochemical properties of PUE toward orally administered drug formulation with improved pharmacokinetics.Keywords:puerarin;L-proline;pharmaceutical co-crystal;crystal structure;solubility and dissolution rate;Chinese traditional medicine;Hirschfeld analysis;hydrogen-bonding
研究领域:
药学
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化学
·
生物医学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2025
·
IF 4.7
Xian-Rui Zhang,Xiao-Han Zhang,Xian-Ying Xie,Jia-Yu Luo,Hui-Jun Chen,Lei Gao
To overcome the limitations of diflunisal (DIF) regarding its solubility and dissolution rate, two different ratios of DIF-piperazine (PIP) salts were synthesized using a salt formation strategy via proton transfer crystallization. The resulting DIF-PIP salts were characterized using various techniques, including crystal structure analysis, powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), and Fourier transform infrared (FT-IR) spectroscopy. The results demonstrated a significant enhancement in solubility for both the DIF-PIP (1:1) and DIF-PIP (2:1) salts when compared to the DIF active pharmaceutical ingredient (API), with increases of 56.5-fold and 3.7-fold, respectively. Notably, the DIF-PIP (1:1) salt exhibited exceptional dissolution performance across various media. Specifically, its dissolution rates in water, pH 6.86 buffer, and pH 9.18 buffer increased by 338.5-fold, 104.8-fold, and 1.5-fold, respectively. This superior dissolution performance suggests potential advantages for pharmaceutical applications, particularly its high dissolution rate in water, which could improve the disintegration and dissolution properties of oral tablets. Additionally, we investigated the polymorphic transformation conditions between DIF-PIP (1:1) and DIF-PIP (2:1) salts in detail, providing both theoretical and experimental insights into controlling the physicochemical stability of pharmaceutical formulations during preparation and storage.
研究领域:
药学
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晶体工程
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药物传递
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固态化学
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2015
·
IF 0.476
Yaping Li,Lili Wang,Yanbei Tu,Jin Yan,Kailin Xu,Hui Li
Emodin (EM), with two p K a values (p K a 1 = 8.0 and p K a 2 = 10.9), presents low solubility and dissolution rate, which results in low bioavailability. In this report, two EM sodium salts, C 15 H 9 O 5 − · N a + (EM-1Na) and C 15 H 8 O 5 2− · 2 N a + (EM-2Na), were prepared by adding various amounts of sodium hydroxide . Salt forms were characterized by FT-IR, XRPD, 1 H NMR, DSC , and SEM, as well as solubility and dissolution rate studies in triple-deionized water, buffer at pH 1.2 and pH 6.8, respectively. The aqueous solubility of EM was notably enhanced by more than 20,000 and 50,000 times, corresponding to EM-1Na and EM-2Na. Meanwhile, the dissolution rate exhibited significant enhancement and the dissolution time was shortened. The results showed the dissolution of EM-1Na and EM-2Na was 25 and 35 times greater than EM in 60 min. The results of β-amyloid (Aβ) self-aggregation inhibition and MIC assay did not show apparent difference from those of EM, indicating that the functional groups were not broken down. Moreover, salt formation significantly enhanced the bioavailability of EM, consistent with the ABTS free radical scavenging test results. The significant decrease in IC 50 values in the range of 18,394 μg/mL to 29.07 μg/mL indicated a more effective anti-AD action.
研究领域:
药剂学
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药物化学
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药物递送
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神经科学
·
微生物学
✓ 已验证
DOI
高影响因子
CHEMICAL ENGINEERING SCIENCE
·
2024
·
IF 4.1
Xiaoxiao Liang,Yanru Wu,Yuehua Deng,Xingye Zeng,Shufeng Shan,Yanbin Jiang,Huaiyu Yang
Multi-component crystal based on supramolecular self-assembly is an effective strategy to modify the physicochemical properties of poorly water-soluble drugs. In this study, eight novel multi-component crystals of Osimertinib (AZD) were firstly synthesized under the guidance of theoretical analysis. Five single crystals were successfully obtained, and the AZD-FMS cocrystal shows a distinctive structure wherein free FMS filled in the skeleton, which may be crucial for maintaining morphology. Analysis of crystal structures and Hirshfeld surfaces indicated the involvement of N−H···O and N···H−O hydrogen bonds in the multi-component crystals. Owing to robust intermolecular interactions, multi-component crystals exhibited improved solubility/dissolution rate compared to pure AZD. Multivariate analysis revealed coformers and strong solute–solvent interactions determined the solubility/dissolution rate. Multi-component crystals showed superior stability in solution and low humidity. Moreover, AZD-FSM increased 5.2-fold anti-tumor activity over AZD, which is anticipated to enhance efficacy, reduce drug toxicity, combat drug resistance, and transform from laboratory to clinical application.
研究领域:
药物化学
·
材料科学
·
癌症研究
✓ 已验证
产品关联
DOI
高影响因子
PHARMACEUTICAL CHEMISTRY JOURNAL
·
2024
·Vol. 57
·期 10
·1627-1636
·
IF 0.8
Liu Lang,Ouyang Fenfen,Li Ting,Wen Min,Zha Guodong,Chen Libo,Fu Xue,Zhu Li qing
Celecoxib, the first cyclooxygenase-2 selective nonsteroidal anti-inflammatory drug, has a wide range of pharmacological effects, including anti-inflammatory, antirheumatic and antitumor effects. However, celecoxib’s poor solubility severely limits its clinical application. Thus, a novel ternary solid dispersion system was developed using PVP K30 and hydroxypropyl-β-cyclodextrin (HPβCD) as carrier materials in order to improve its solubility and dissolution behavior. The solid dispersion system was characterized by SEM, XRD, FT-IR, DSC, in vitro dissolution, saturated solubility, and contact angle test; the stability of the samples under extreme environments was investigated as well. The results showed that the novel ternary solid dispersion doped with PVP K30 and HPβCD has enhanced solubility around 6.28-fold, an almost 13.94-fold increase in the dissolution rate (120 min) compared with celecoxib’s active pharmaceutical ingredient. The substantial improvement in its dissolution performance is attributed to the fact that celecoxib is dispersed in the carrier material in an amorphous form and has hydrogen bonding interactions with the carrier materials. In addition, the improvement of wettability is one of the reasons for its increased solubility. In conclusion, the combination of PVP K30 and HPβCD can significantly improve the solubility of celecoxib and this novel solid dispersion system provides new ideas and methods to further improve the solubility of insoluble drugs.
研究领域:
药剂学
·
药物技术
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药物传递
·
材料科学
·
生物药剂学
✓ 已验证
DOI
高影响因子
CHEMICAL ENGINEERING SCIENCE
·
2022
·
IF 4.889
Yuehua Deng,Wenhao Deng,Wenquan Huang,Zhiyong Zheng,Rui Zhang,Shiyuan Liu,Yanbin Jiang
Amorphization technology has been a promising strategy to improve the solubility and dissolution of drugs. This study aims to prepare norfloxacin (NFX) co-amorphous (CA) systems and evaluate the association between molecular descriptors and the formation and physical stability of NFX CAs. The molecular miscibility between NFX and 17 co-former candidates was firstly predicted using Hansen solubility parameters (HSPs) and six NFX CAs were successfully prepared by dry ball mill. Compared with crystalline NFX, four NFX CAs showed enhanced solubility (up to 2.50-fold) and dissolution rates. NFX CAs exhibited excellent physical stability under dry conditions. According to the quantitative calculations of Pearson correlation coefficient and Ridge regression, molecular descriptors have a great effect on NFX CA formation with structural parameters (Weight, VDW_vol, VDW_area, Rings) stronger than miscibility parameter Δ δ ¯ and p K a. These molecular descriptors corresponding to π···π interactions, molecular miscibility and ionic interactions are also responsible for physical stability. The results demonstrate that NFX CA can be stably formed if the co-former has more rings, smaller Δ δ ¯ (less than or close to 5 MPa 0.5 ) and larger Δp K a. This study offers a potential strategy to screen and design a CA system using multivariate data analysis based on theoretical considerations of molecular descriptors.
研究领域:
药学
·
材料科学
·
药物递送系统
·
药剂学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Yan Wang,Xiaodi Yang,Jianguo Luo,Sisi Yi,Tao Guo,Yue Liao,Chao Yu,Xiangjun Zhang
Piroxicam (PX) is a nonsteroidal anti-inflammatory drug (NSAID) commonly associated with gastrointestinal (GI) injuries, including dyspepsia, heartburn, inflammation, bleeding, ulceration, and life-threatening perforation. The β-cyclodextrin (β-CD)-based PX formulation (PX@CD) has been shown to reduce gastric side effects by improving PX’s solubility and dissolution rates. However, the solubility of PX can only be increased to a limited extent by β-CD, due to the low binding constant between PX and β-CD (∼100 M −1 ). As a result, adverse reactions such as epigastric pain and pyrosis are still commonly reported. Cucurbit[7]uril (CB[7]) is a synthetic macrocyclic host compound that binds strongly to various drugs. In this study, we demonstrated that CB[7] forms complexes with PX in the gastric acid environment with a binding constant approximately 70 times higher than that between β-CD and PX. The PX@CB[7] inclusion complexes exhibited rapid dissolution rates in the gastric environment. In addition, PX@CB[7] showed significantly higher oral bioavailability and maximum concentration (C max ) compared to PX and PX@CD (1:2.5), resulting in improved anti-inflammatory effects in both mouse and rat models. Moreover, PX@CB[7] (1:2.5) had the least adhesion to the gastric mucosa and caused the mildest gastric side effects in rat models when compared to PX, PX@CD (1:2.5), and PX@CB[7] (1:1). Lastly, CB[7] demonstrated good oral biocompatibility in a subacute toxicity evaluation study. These findings indicate that CB[7] could be used as an excipient to improve treatment effectiveness and decrease adverse reactions in orally administered formulations with a favorable safety profile.
研究领域:
药学
·
药物递送系统
·
药理学
·
毒理学
✓ 已验证
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）