JOURNAL OF THE CHINESE CHEMICAL SOCIETY
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2023
·Vol. 70
·期 4
·956-966
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IF 1.8
Muhammad Inam,Chi Uyen Phan,Jian-Wei Wang,Muhammad Jamshed,Xiurong Hu,Guping Tang
Drug solubility plays a significant role in the development of drug formulation. The objectives of this work are to improve the solubility and dissolution rate of vortioxetine (VT) by preparing its inclusion complexes (ICs) with β-Cyclodextrin (β-CD) and γ-Cyclodextrin (γ-CD). The ICs were prepared in 1:1 M ratio via recrystallization method and characterized by P-XRD, FT-IR, 1 H NMR, 2D NOESY, and DSC. Further, the crystal structure of VT-β-CD was analyzed by SC-XRD. P-XRD data obtained for ICs describe the crystalline pattern. The DSC analysis shows change in the thermal behavior of VT, CDs and ICs. FT-IR analysis shows shifting of frequencies in ICs when compared with the pristine VT drug and CDs. The 2D NOESY in DMSO-d 6 indicates weak interaction between the VT and CD molecules. The crystal structure of VT-β-CD consists of one guest VT, one host CD, and nine water molecules in the crystal lattice. The solubility of ICs was significantly improved in distilled water, pH 1.2 acidic, and phosphate buffer pH 6.8 medium, as compared with the solubility of the pristine VT drug. The in vitro dissolution rate of ICs in different dissolution media was investigated, which was higher than that of the commercial product of VT.
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
MOLECULES
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2019
·Vol. 24
·期 9
·1770
·
IF 3.06
Cuiyan Han,Haitao Huang,Yan Dong,Xiaoyu Sui,Baiyu Jian,Wenquan Zhu
Mesoporous carriers have been extensively applied to improve the dissolution velocity and bioavailability of insoluble drugs. The goal of this work was to compare the drug-loading efficiency (LE) and drug-dissolution properties of mesoporous silica nanoparticles (MSN) and mesoporous carbon nanoparticles (MCN) as drug vectors oral delivery of water-insoluble drugs. For this purpose, MSN and MCN with similar particle size, surface area, and mesoporous diameter were prepared to precisely evaluate the effects of different textures on the drug-loading and dissolution behavior of insoluble drugs. Carvedilol (CAR), a Bio-pharmaceutic Classification System (BCS) class II drug, was loaded in the MSN and MCN by the solvent adsorption method and solvent evaporation method with different carrier–drug ratios. The carboxylated MCN (MCN–COOH) had a higher LE for CAR than MSN for both the two loading methods due to the strong adsorption effect and π–π stacking force with CAR. In vitro drug dissolution study showed that both MSN and MCN-COOH could improve the dissolution rate of CAR compared with the micronized CAR. In comparison to MSN, MCN-COOH displayed a slightly slower dissolution profile, which may be ascribed to the strong interaction between MCN-COOH and CAR. Observation of cell cytotoxicity and gastrointestinal mucosa irritation demonstrated the good biocompatibility of both MSN and MCN–COOH. The present study encourages further research of different carriers to determine their potential application in oral administration.Keywords:mesoporous silica;mesoporous carbon;carvedilol;in vitro dissolution;water–insoluble drug
研究领域:
药剂学
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生物医学工程
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材料科学
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产品关联
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
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2022
·
IF 2.65
Mingyi Sun,Yaolei Li,Ying Wang,Huimin Wu,Jing Liu,Longtai You,HuLinyue Peng,Huating Huang,Hongyu Jin,Xiaoxu Dong,Changhai Qu,Xingbin Yin,Jian Ni
At present, several experiments have been carried out to study the changes in total arsenic content of realgar and its prescription, but few researches on its form and valence. We evaluated the change in arsenic species concentration in realgar from the perspective of absorption by using an in vitro dissolution study, an in vivo unidirectional intestinal perfusion study, transmembrane transport in Caco-2 cells, and a pharmacokinetic study in rats. In the gastrointestinal tract, arsenic species are mainly present inorganic forms of AsIII and AsV. The cumulative dissolution rates of soluble arsenic in 4 h artificial gastric fluid and 8 h artificial intestinal fluid were 21.99% and 59.20%, respectively. The values of soluble arsenic in realgar in the duodenum, jejunum, and ileum of rats were 5.4 × 10−3, 6.1 × 10−3 and 5.8 × 10−3 cm/min, respectively. In the process of small intestine perfusion, the AsIII of realgar was partially converted into AsV in the duodenum and jejunum. As the transport time increased, the transmembrane transport rate and value of soluble arsenic in realgar were increased in Caco-2 cells, and it also suggested that arsenic species may be passively transported across the Caco-2 cell monolayer. The Cmax and AUC (0-24) of AsIII, AsV, and DMA in plasma of realgar were 41.26 ng L−1/343.977 ng h mL−1, 21.626 ng L−1/47.310 ng h mL−1, and 2.372 ng L−1/30.429 ng h mL−1, respectively. Tmax and MRT (0-∞) of AsIII, AsV, and DMA were 2.571 h/9.649 h, 0.393 h/2.790 h, and 3.143 h/23.145 h, respectively. It is hoped to provide a basis for clarifying the arsenic species in realgar.
研究领域:
药学
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毒理学
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药理学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2023
·
IF 4.9
Fulong Man,Yinqian Yang,Haisheng He,Jianping Qi,Wei Wu,Yi Lu
In vitro dissolution that predicts the in vivo performance of solid preparations is extremely important in formulation optimization. Fraction absorbed (Fa) has been used to screen in vitro dissolution protocols based on the idea of in vitro–in vivo correlation (IVIVC) but failed to increase the success rate due to the inaccuracy of the Fa. The essence of IVIVC is the correlation between in vitro dissolution and in vivo dissolution. We tried to establish in vitro dissolution protocol via similarity with in vivo dissolution using aripiprazole (APZ) as a model drug. Hybrid APZ crystals (APZ-HCs) were prepared by physically embedding aggregation-caused quenching (ACQ) fluorophores inside the lattice to measure the in vivo dissolution. The process did not change the physicochemical properties and crystallinity of APZ. The fluorophore illuminated APZ crystals but was quenched upon dissolution of APZ-HCs in aqueous media, enabling monitoring intact APZ-HCs in real-time. The good correlation between fluorescent quenching and dissolution of APZ-HCs justified reliable quantification of intact APZ crystals. The residual percentage of fluorescence intensity in rats treated by APZ-HCs was recorded with time, which was converted to in vivo dissolution by the difference from 100%. The in vivo dissolution was validated with the Fa. The in vitro dissolution profile of APZ was set up via a similarity factor larger than 50 in comparison with the in vivo dissolution. The study provides a novel idea and method to establish in vitro dissolution protocol.
研究领域:
药剂学
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药物递送系统
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药学
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产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
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2020
·
IF 4.902
Junqiu Zhai,Zhanlun Ou,Liuting Zhong,Yu-e Wang,Li-Ping Cao,Shixia Guan
The glucagon-like peptide-1 receptor agonist exenatide (EXT) is an effective treatment for type 2 diabetes. However, this peptide has a short biological half-life and the delayed release characteristic of current formulations limit its clinical application. Herein, we prepared EXT-loaded inside-porous poly(d,l-lactic-co-glycolic acid (PLGA) microspheres with outside layers (EXT-PMS) using a W1/O/W2 emulsion method with a microfluidic technique and its fabrication and formulation conditions were systematically investigated. In vitro dissolution experiments showed that the PLGA concentration, proportion of drug and oil phase, and the number and size of pores strongly affected the release behaviors of EXT-PMS. In vitro, the optimized EXT-PMS with large internal pores exhibited rapid and stable release without a lag phase. In a rat model, subcutaneous administration of the product yielded plasma concentrations of EXT that was sustained for 30 days with low burst and no delayed-release effect. The preparation of inside-porous microspheres is lighting up the development of long-acting drug delivery systems for other drugs with favorable release characteristics.
研究领域:
药剂学
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药物递送系统
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生物药剂学
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制药技术
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2020
·
IF 2.734
Rui Bao,Qi-Long Wang,Ran Li,Michael Adu-Frimpong,Elmurat Toreniyazov,Hao Ji,Xi-Ming Xu,Jiang-Nan Yu
6-Shogaol is one component of ginger, which has been described to possess various health-promoting effects including anticancer, antiinflammatory, antioxidant and antiatherogenic. However, poor water solubility has limited the aforementioned health benefits and clinical applications of the drug. Herein, the aforementioned drawback was circumvented by the preparation of 6-shogaol-loaded liposome through thin-film dispersion method with TPGS as the carrier, in comparison with 6-shogaol liposome and free 6-shogaol. Appropriate indices were used for the characterization of the developed liposomes viz., particle size (PS), zeta potential (Z-potential), polydispersity index (PDI), entrapment efficiency (EE) and loading capacity (LC) while their morphologies were observed under the transmission electron microscopy (TEM). In-vitro dissolution investigation showed a substantial improvement in the accumulative release rates of liposomes comparable to the free 6-shogaol. The TPGS-modified 6-shogaol and 6-shogaol liposomes had oral relative bioavailability (RBA) of 580.04% and 281.55%, respectively, with improved t 1/2 , MRT, C max , AUC 0-t and T max . Pertinently, the TPGS coated 6-shogaol liposome may enhance the targeting of the drug to the brain. Therefore, the TPGS coated 6-shogaol liposome could potentially improve oral bioavailability of lipophilic drug in-vivo . More importantly, the results of tissue distribution investigation suggest that TPGS coated 6-shogaol liposome may act as promising carrier for brain delivery in future.
研究领域:
药剂学
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药理学
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纳米技术
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药物递送系统
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）