ADVANCED FUNCTIONAL MATERIALS
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2026
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IF 19.9
Shan Wang,Yabing Hua,Jijun Yu,Xudong Dai,Yuhua Ran,Wenpeng Zhang,Yanan Zhai,Zhiping Li,Xiaomei Zhuang,Jing Gao
Thorough understanding and accurate prediction of in vivo drug release are essential for developing long-acting microsphere systems. However, the fate of microspheres after prolonged tissue residence and the regulatory role of physiological factors remain unclear, hindering elucidation of release mechanisms. Herein, the dynamic evolution of microsphere depots and associated microenvironmental changes were studied. Beyond poly(lactic-co-glycolic acid) (PLGA) and API effects, microsphere depot behavior is partly regulated by conserved biological processes, with skeletal muscle and subcutaneous tissue employing distinct adaptive strategies to restore homeostasis. Using these insights, we developed the in vivo release predictive models (IVRPMs) that establish a true IVIVC for naltrexone PLGA microspheres. The IVRPMs demonstrated broad applicability across microspheres with different APIs and PLGA types, and showed promising translational potential in beagle and human studies. This study shifts the research paradigm from “material-dominated release” to “organism-material coevolution”, addressing a key question in depot formulation fate.
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DOI
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
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2021
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IF 3.517
Song Yang,Mengya Hu,Wenqing Liu,Nuohan Hou,Kaidi Yin,Chen Shen,Qing Shang
In this study, a novel PLGA in situ forming implants (ISFIs) were fabricated and methods for testing the in vitro release profiles were also developed. The correlations between in vitro release profiles and in vivo performances (in vitro–in vivo correlation, IVIVC) were also studied. PLGA with different molecular weights were selected as the polymeric matrix. Biocompatible N-methy1-2-pyrrolidone (NMP) or glyceryl triacetate (GTA) were used as the solvents with the ratios of NMP/GTA from 60/40 (vol/vol) to 20/80 (vol/vol). Eprinomectin (EPR) was chosen as the model therapeutic. In vitro release profiles of the EPR-loaded PLGA ISFIs were investigated using various methods (i.e. ‘tubule’ sample-and-separate and dialysis method). Sprague–Dawley rats were used to study the in vivo pharmacokinetics of EPR-loaded PLGA ISFIs. The release data obtained via ‘tubule’ sample-separate method had a good IVIVC (Level A, R2 > 0.99). These results showed that the ‘tubule’ sample-separate method was capable of discriminating the EPR-loaded ISFIs which were equivalent in formulation composition with manufacturing differences. Meanwhile, this method could be used to predict the in vivo performances of ISFIs in the investigated animal model.
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
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
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2022
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IF 5.589
Sicheng Yao,Naiying Chen,Mingming Li,Qiuyue Wang,Xinxing Sun,Xun Feng,Yang Chen
The study aimed to explore the size effect on the in vitro-in vivo correlation (IVIVC) in the oral absorption of andrographolide nanosuspensions (Ag-NS). Ag-NS with controllable particle sizes were prepared by ultrasonic dispersion method, and the formulation and process parameters were optimized through single factor experiments using mean particle size, polydispersity index, and stability as evaluation indicators. The morphology of Ag-NS was observed by scanning electron microscopy (SEM), and the crystalline state of the nanosuspensions was characterized by X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC). The dissolution tests were carried out with the paddle method in two different mediums simulating the pH conditions in intestinal fluid (pH 6.8) and gastric fluid (pH 1.2), respectively. The pharmacokinetic behaviors were investigated in rats after oral administration, and a deconvolution approach was introduced to determine the correlation between in vitro dissolution and in vivo absorption (IVIVC). The formulation with the use of lecithin and PEG-800 as stabilizers showed its potential in the size-controllable preparation of Ag-NS. Via altering the ultrasonication amplitude and time, three Ag-NS suspensions with three particle sizes, i.e., Ag-NS 250 (249.8 ± 1.3 nm), Ag-NS 450 (485.2 ± 3.7 nm), Ag-NS 1000 (1015 ± 36.1 nm) were prepared. Their morphological and crystal characteristics were not changed during the size reduction process, but both of their in vitro dissolution and in vivo absorption were improved. Relatively better IVIVC performance was observed with the in vitro dissolution data at pH 6.8 ( r > 0.9). With the reduction of particle size, the in vivo absorption fraction was more closed to the level of the in vitro dissolution. In conclusion, the decrease in particle size would improve the dissolution and absorption of Ag-NS, and also affect their IVIVC performance. The study would facilitate the design and quality control of Ag-NS in terms of particle size and dissolution specifications.
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
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2023
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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
✓ 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）