JOURNAL OF APPLIED POLYMER SCIENCE
·
2019
·Vol. 136
·期 24
·47662
·
IF 2.188
Yulong Xu,Kaili Li,Yong Liu,Yan An,Changmin Xing
Black plaster is a traditional Herbal medicine with a long history; it is usually used in paste form. In this study, a black plaster/poly(ethylene glycol) (PEG) composite fiber was prepared by a novel upward melt electrospinning method. Scanning electron microscopy results show that the black plaster composite fiber has good morphology and uniform diameter. Thermogravimetric analysis results indicate that the heating temperature in the electrospinning process does not damage the composition of the black plaster, and drug components are effectively retained in the black plaster. Drug dissolution results show that the dissolution of poorly water-soluble Draconis Sanguis in both pure black plaster fibers and composite fibers are significantly higher than that in traditional bulk black plasters. When the PEG content in the composite fiber is 85 wt %, the drug dissolution amount of Draconis Sanguis in the black plaster composite fiber is the highest. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136 , 47662.
研究领域:
材料科学
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中药学
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制药工程
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产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Wei Gu,Qinfu Zhao,Ye He,Shengyu Wang,Yuanqi Yang,Yian Li,Shuaipeng Feng,Siling Wang
Mesoporous carriers have gained significant attention for enhancing the solubility and bioavailability of Biopharmaceutics Classification System (BCS) Class II drugs. However, the contribution of mesoporous carriers with varying morphologies to the physical stability of these drugs is not well-defined. In this work, mesoporous carbon nanoparticles (MCN) and hollow carbon mesoporous nanoparticles (HMC) were prepared, while the weakly acidic Indomethacin (IMC) and alkaline Celecoxib (CXB) were incorporated into these carriers in the amorphous state by the solvent evaporation method. Notably, HMC demonstrated superior drug loading efficiencies (approximately 43 %) for both IMC and CXB owning to its hollow structure. The mesoporous drug loading systems significantly enhanced dissolution rates in comparison with both self-made amorphous drugs and raw drugs. Furthermore, under accelerated and long-term storage conditions, the mesoporous carriers effectively prevented drugs loaded from crystallization, maintaining constant dissolution profiles for over 12 months. Intriguingly, CXB exhibited a slower rate of crystallization after loading into the mesoporous carriers, likely due to the formation of hydrogen bonds between the carbonaceous carrier material and the amino groups of CXB. Compared with loaded drugs, the self-made amorphous drugs exhibited a crystallinity increase beyond 60 % within the initial month. Collectively, these findings highlighted the potential of mesoporous carbon carriers to elevate the dissolution behaviors of BCS Class II drugs while preserving the physical stability of the loaded amorphous drugs.
研究领域:
药剂学
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材料科学
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产品关联
DOI
PubMed
高影响因子
DRYING TECHNOLOGY
·
2023
·
IF 3.3
Yanchao Li,Haosen Zhang,Tianwei Zhang,Tao Liu
This study aimed to produce nanoparticles with reduced crystallinity by using a combination method. The effect of solid-state transition (different drying processes) coupled with particle size reduction (homogenization) on drug dissolution was systematically investigated. Meloxicam, indomethacin and naproxen with different X-ray diffraction crystal intensity (relative high, medium and low) were selected as models. All drugs were first processed with and without polyvinylpyrrolidone (PVP) to obtain solid dispersions and then high pressure homogenization was used to produce nanosuspensions. Changes of particle morphology might be an important factor to improve the nanosizing efficiency. The smallest particle size (188 nm) could be obtained by using freeze-dried naproxen coupled with PVP after 20 homogenization cycles. Dissolution rates of processed indomethacin and meloxicam without PVP were found similar to their raw drugs. However, significant dissolution improvements were found after homogenization (higher than nanocrystals). Dissolution values of three drug nanoparticle achieved by using PVP dispersions were all higher than 83%. For naproxen, although nanosized solid dispersion possessed the smallest size and amorphous state, its dissolution curve was comparable to the larger sized nanocrystals. It was inferred that the relatively low crystal intensity of the initial compound could be the reason. Nanosuspensions of indomethacin and meloxicam prepared by using the two-step method showed optimized dissolution compared to their nanocrystals and amorphous solid dispersions.
研究领域:
药剂学
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材料科学
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产品关联
DOI
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2020
·
IF 5.88
Qiankun Jiang,Lingqiong Wu,Yue Zheng,Xiaojie Xia,Ping Zhang,Tong Lu,Jing Li
To combine the advantages of micelles and biomimetic silica materials, biomimetic micellar mesoporous silica xerogel (BM-SX) was initially established, biomimetic silica xerogel (B-SX) was also studied as control and nitrendipine (NDP) was taken as model drug. The content mainly focused on drug dissolution, systemic stability and cellular transmembrane transport of NDP loaded B-SX and NDP loaded BM-SX. With extra mesopores formed due to HPMC E50 micelles, the mean pore diameter, surface area and pore volume of BM-SX were all larger than B-SX. After loading NDP into the two carriers, crystal NDP changed to amorphous phase, leading to enhanced NDP dissolution. BM-SX presented superior abilities not only for its higher drug dissolution compared to B-SX but also for its capacity in remaining high amorphous drug phase and therefore no drug dissolution reduction can be observed. The dynamic contact angle result confirmed the strong power of HPMC E50 micelles in maintaining amorphous NDP in the carrier to improve high systemic stability. Both B-SX and BM-SX could increase drug absorption permeability and exert function as drug efflux inhibitor to inhibit the efflux effect of p-gp drug pump and promote NDP absorption and transport, and BM-SX was superior owing to micelles in the system.
研究领域:
药剂学
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材料科学
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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
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2016
·
IF 3.994
Qiao Xing,Jia Song,Xiuhua You,Dongling Xu,Kexin Wang,Jiaqi Song,Qin Guo,Pengyu Li,Chuanbin Wu,Haiyan Hu
Drug solubility and lymphatic transport enhancements are two main pathways to improve drug oral bioavailability for microemulsions . However, it is not easy to have both achieved simultaneously because excipients used for improving lymphatic transport were usually insufficient in forming microemulsions and solubilizing drugs. Our research is to explore whether ethyl oleate , an oil effective in developing microemulsions with desired solubilizing capability, could increase bioavailability to a higher extent by enhancing lymphatic transport. As a long-chain oil, ethyl oleate won larger microemulsion area than short-chain tributyrin and medium-chain GTCC. In contrast, long-chain soybean oil failed to prepare microemulsions. The solubility of piroxicam in ethyl oleate microemulsions (ME-C) increased by about 30 times than in water. ME-C also won significantly higher AUC 0−t compared with tributyrin microemulsions (ME-A) and GTCC microemulsions (ME-B). Oral bioavailability in ME-C decreased by 38% after lymphatic transport was blocked by cycloheximide , severer than those in ME-A and ME-B (8% and 34%). These results suggest that improving lymphatic transport and solubility simultaneously might be a novel strategy to increase drug oral bioavailability to a higher extent than increasing solubility only. Ethyl oleate is a preferred oil candidate due to its integrated advantages of high solubilizing capability, large microemulsion area and effective lymphatic transport.
研究领域:
药剂学
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药物代谢动力学
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生物医学工程
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2023
·
IF 5.8
Qiang Huang,Zhiren Zou,Xiaobo Li,Qinwen Xiao,Guang Liang,Wenqi Wu
The drug-amino acid co-amorphous systems and amorphous solid dispersions (ASDs) are promising methods to address the poor water solubility of poorly water-soluble drugs. However, some amino acids might not be perfect co-formers for co-amorphous systems, and the relatively low drug-loading of many ASDs is one of the main disadvantages of ASDs. Thus, poly- l -lysine and polyglutamic acid were selected as the co-formers, ball milled with basic mebendazole, neutral tadalafil and acidic valsartan at different weight ratios (from 3:1 to 1:3) to prepare poly (amino acid)-based ASDs, aiming to combine the advantages of co-amorphous systems (high drug-loading) and ASDs (relatively high T g and high physical stability). All the mixtures were converted into amorphous after milling. The powder dissolution studies showed that drug-poly (amino acid) ASDs improved the dissolution rate of the drug in different ways and to different degrees. Moreover, the two poly (amino acid)s enhanced the physical stability of amorphous drugs. It is worthy to mention that the salt formation between the drug and the poly (amino acid) does not necessarily mean better performance compared to non-salt forming systems, and salt formation is also not a prerequisite for the formation of promising drug-poly (amino acid) ASDs.
研究领域:
药剂学
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材料科学
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生物化学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2023
·
IF 15.1
Gang Wei,Yubin Yao,Hongbo Zhang,Wenguo Cui,Yong Lu
Organic drug small molecules with rigid π-electron conjugated structures have relatively strong dipole–dipole and π-π stacking interactions causing the drug aggregation in solution, the efficacy of which is limited. In this study, molecular aggregation was inhibited by increasing the spacing of organic molecules to more than 7 Å. Thiol-polyhedral olisesquioxane (POSS-SH) with eight active sites was selected as a stabilizer to increase the molecular spacing through a large number of density functional theory (DFT). After non-pharmacologically acting amino/hydroxyl groups in poorly soluble drugs was double-bonded with acryloyl chloride. The drugs were modified by POSS-SH through “click chemistry” to increase molecular spacing, so as to prevent π - π stacking and charge transfer. DFT and spectroscopic property studies showed that the molecular spacing of the drug modified by POSS-SH exceeded 8.063 Å, the increased spacing effectively inhibited the H- or J-aggregation then increasing the solubility of poorly soluble molecules to greater than 6.24 g/100 g (H 2 O). The introduction of POSS-SH improved the solubility of insoluble molecules and so the therapeutic effects exerted by POSS-SH-modified hybrid molecules on cells were superior to the unmodified drug. Improving the solubility of insoluble drugs through POSS-SH may represent an important breakthrough in small-molecule drug research and development.
研究领域:
药学
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材料科学
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有机化学
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产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
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2023
·
IF 4.6
Zhiren Zou,Qiang Huang,Xiaobo Li,Xianzhi Liu,Lina Yin,Yunjie Zhao,Guang Liang,Wenqi Wu
Co-amorphous systems have been proven to be a promising strategy to address the poor water solubility of poorly water-soluble drugs. Generally, the initial dissolution behaviors after co-amorphous system preparation and the potential recrystallization during storage are used to evaluate the performance of co-amorphous systems. However, this study reveals that decreased dissolution and unexpected increased dissolution were observed during storage though the co-amorphous systems maintained amorphous form. Three drugs (valsartan, tadalafil, mebendazole) and three co-formers (arginine, tryptophan, biotin) were used to prepare co-amorphous systems and the samples were stored for different times. After stored for 80 d, most of the co-amorphous systems maintained amorphous form, however, decreased and increased intrinsic dissolution rates (IDRs) were both observed in these non-recrystallized co-amorphous systems. The moisture changes of the systems during storage and the possible drug-co-former molecular interactions showed no effect on the dissolution changes, while phase separation might play a role in it. In conclusion, more attention should be paid to the dissolution changes of co-amorphous systems during storage. Focusing on the initial dissolution behaviors after sample preparation and the physical recrystallization during storage is not enough for the development of co-amorphous systems in future.
研究领域:
药剂学
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药物化学
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产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2022
·Vol. 23
·期 7
·1-10
·
IF 4.026
Lv Jianhua,Ou Xiaoyu,Fang Yaru,Wu Mi,Zheng Fanghao,Shang Lei,Lei Kaijun,Liu Yunen,Zhao Yan
Deep eutectic solvents (DESs) based on choline chloride (C) and l -(+)-tartaric acid diethyl ester (L) were prepared and used in transdermal drug delivery system (TDDS). The internal chemistry structure including the formation and changes of hydrogen bonds of choline chloride and l -(+)-tartaric acid diethyl ester DES was characterized via attenuated total reflection Fourier transform infrared (ATR-FTIR) and 1 H nuclear magnetic resonance ( 1 H NMR) spectroscopy. The stoichiometric ratio of choline chloride to l -(+)-tartaric acid diethyl ester as well as water content affected the viscosity, glass transition temperature ( T g ), and drug solubility of the DES. The viscosity and glass transition temperature of the DES (CL14) prepared at the ratio of 1:4 of choline chloride to l -(+)-tartaric acid diethyl ester were 1.19 Pa·s and − 44.01°C, respectively, and decreased to 0.10 Pa·s and − 55.31°C when 10% water (CL1410) was added. Taking diclofenac diethylamine (DDEA), the nonsteroidal anti-inflammatory drug as model, drug solubility was as high as 60 mg/ml and 250 mg/ml in CL14 and CL1410, respectively. The cumulative amount of DDEA was 4.63 ± 2.67 μg/cm 2 and 15.27 ± 4.63 μg/cm 2 for CL14 and CL1410, respectively, at 8 h. The mechanism of percutaneous permeability by the DES may be the disturbance of stratum corneum (SC) lipids as well as changes in the protein conformations. CL14 and CL1410 were also verified as low-cytotoxic and nonirritant. Therefore, the DESs studied are promising to be used in drug solubilization enhancement and transdermal drug delivery system. Graphical abstract
研究领域:
药剂学
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生物医学工程
·
化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Shuai Zhang,Jiaxu Wu,Peng Sun,Liang Fang
Novel hydroxyphenyl adhesives (HP-PSAs) could significantly increase drug solubility and control drug release through a doubly ionic hydrogen bond (DIH bond) in the patch. However, chemical penetration enhancers (CPEs) always destroy the performance of most adhesives. As a result, this work investigated the stability of both the HP-PSA features and the DIH bond under the interference of the CPEs. Donepezil (DON) was chosen as the model drug, and CPEs with hydroxyl, carboxyl, amido, and ester groups were selected as model CPEs. Unlike the commonly used neutral H-bond, the DIH bond between DON and the HP-PSA was still stable under the interference of the CPEs, resulting in the 2–3-fold drug solubility in the HP-PSA, which was higher than that in the nonfunctional PSA, which reduced the drug crystallization risk and the difficulty of formulation design. FT-IR, 1H NMR, XPS, dynamic simulation, and molecular docking revealed the mechanism of the stability feature of both the DIH bond and the high drug solubility of the HP-PSA, which was that the formed neutral H-bond interaction caused by CPEs is weaker than that of the DIH bond between DON and the HP-PSA. Furthermore, the drug release, skin permeation, and CPE release study showed that the newly formed weak H-bond and strong ionic H-bond interaction promoted or controlled both DON and CPE release, respectively, thereby influencing drug skin permeation, which provided a theoretical basis for drug release regulation. To summarize, besides the reversible, strong features of the DIH bond in our previous study, the stability of the interaction made the HP-PSA’s high drug solubility potential to be applied in the TDDS.
研究领域:
药学
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材料科学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2023
·Vol. 24
·期 7
·1-12
·
IF 3.3
Lv Jianhua,Wu Pan,Fang Yaru,Zhang Wenchang,Liu Dongwen,Wu Mi,Shang Lei,Li Huaiguo,Zhao Yan
By selecting L-arginine as the hydrogen bond acceptor (HBA) and 2-hydroxypropyl-β-cyclodextrin (2HPβCD) as the hydrogen bond donor (HBD), deep eutectic solvents (DESs) with various water content were prepared at the 4:1 mass ratio of L-arginine to 2HPβCD with 40 to 60% of water, and were studied for its application in transdermal drug delivery system (TDDS). The hydrogen bond networks and internal chemistry structures of the DESs were measured by attenuated total reflection Fourier transform infrared (ATR-FTIR) and 1 H-nuclear magnetic resonance spectroscopy ( 1 H-NMR), which demonstrated the successful synthesis of DESs. The viscosity of DES was decreased from 10,324.9 to 3219.6 mPa s, while glass transition temperature (Tg) of the DESs was increased from − 60.8 to − 51.4 °C, as the added water was increased from 45 to 60%. The solubility of ibuprofen, norfloxacin, and nateglinide in DES with 45% of water were increased by 79.3, 44.1, and 3.2 times higher than that in water, respectively. The vitro study of transdermal absorption of lidocaine in DESs showed that the cumulative amounts of lidocaine reached 252.4 µg/cm 2 , 226.1 µg/cm 2 , and 286.1 µg/cm 2 at 8 h for DESs with 45%, 50%, and 60% of water, respectively. The permeation mechanism of DES with lower content of water (45%) was mainly by changing the fluidization of lipids, while changing the secondary structure of keratin in stratum corneum (SC) at higher water content (50% and 60%). These nonirritant and viscous fluid like DESs with good drug solubility and permeation enhancing effects have broad application prospect in the field of drug solubilization and transdermal drug delivery system. Graphical Abstract
研究领域:
药剂学
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药物递送系统
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药物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Veterinary Science
·
2025
·
IF 2.9
Yanling Sun,Yanan Mao,Xin He,Xinghua Zhao
The aim of this study was to prepare polymeric micelles composed of enrofloxacin (ENR) and methoxy poly (ethylene glycol)-poly(lactide) (mPEG-PLLA) using a solvent evaporation method to overcome the solubility-limited oral bioavailability of ENR. The formulation was optimized using a Box–Behnken design (BBD) to obtain ENR polymeric micelles (ENR-m) with high drug loading (DL, %) and entrapment efficiency (EE, %). The physicochemical properties, in vitro drug release, pharmacokinetics, and antibacterial efficacy were evaluated in comparison to pure ENR. ENR-m was successfully prepared and demonstrated satisfactory drug loading (68.38 ± 0.22%), entrapment efficiency (88.40 ± 0.91%), particle size (PS) (133.67 ± 3.10 nm), and polydispersity index (PDI) (0.13 ± 0.03). The ENR-m also exhibited excellent stability under environmental conditions (40°C and 75% relative humidity (RH)). In vitro release of ENR from micelles was accelerated in a PBS solution. A pharmacokinetic study on beagles revealed that the oral bioavailability of ENR-m was enhanced by approximately 1.60-fold compared to pure ENR (p < 0.01) and by 1.66-fold compared to commercially available tablets of ENR (p < 0.01). The antibacterial activity of ENR-m against Escherichia coli (E. coli) and Salmonella typhi (S. typhi) was stronger than that of pure ENR.
研究领域:
药剂学
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药理学
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微生物学
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高分子科学
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药物传递
✓ 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）