SEPARATION AND PURIFICATION TECHNOLOGY
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2024
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IF 8.1
Longping Jiang,Wenqian Chen,Limin Zhou,Li Xu,Feiqiang He,Jerry Y.Y. Heng,Hamza Shehzad,Jinbo Ouyang
The study of crystal growth and regeneration mechanisms is of great significance for controlling the morphology of crystals. Through the investigation of the recovery and regrowth processes of crystals, we have revealed the regeneration mechanism of aceclofenac (ACF) crystals and the influence of hydroxypropyl methylcellulose (HPMC) on the regeneration of ACF crystals. Firstly, ACF crystal regeneration experiments were conducted in acetone (ACT) and methyl acetate (MA), and it was found that the broken crystals could be successfully regenerated and restored to their original morphology, the regenerated ACF crystals in MA exhibited a larger aspect ratio. Secondly, the crystals obtained from the two solvents were placed in different solvents for regrowth, and it was shown that solvent was a key factor influencing the aspect ratio of ACF crystals. Additionally, HPMC was used to regulate the crystal morphology , it was found that the best effect was achieved when the mass fraction of HPMC was 0.5%, resulting in a regenerated crystal with an aspect ratio of only 2.19. Molecular simulation results indicated that the interaction between the radial (1 1 0) crystal facet and the solvent was weaker than that with the axial (1 0 -1) crystal facet, leading to a higher radial growth rate and a larger aspect ratio of the crystal. However, after adding HPMC, the interaction between HPMC and the radial (1 1 -1) and (1 1 0) crystal facets became stronger. HPMC selectively adsorbed on these two crystal facets, ultimately resulting in crystals with a smaller aspect ratio. The research findings of this study will provide theoretical basis for solving the problem of difficult morphology control due to crystal fragmentation in the pharmaceutical industry production process.
研究领域:
药学
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晶体工程
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产品关联
DOI
高影响因子
International Journal of Nanomedicine
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2020
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IF 5.115
Chen Jianxian,Kalsoom Saleem,Muhammad Ijaz,Masood Ur-Rehman,Ghulam Murtaza,Mulazim Hussain Asim
Aim Chronic use of oral nonsteroidal anti-inflammatory drugs (NSAIDs) is commonly associated with gastric irritation and gastric ulceration. Therefore, the aim of study was to develop a novel oral drug delivery system with minimum gastric effects and improved dissolution rate for aceclofenac (ACF), a model BCS class-II drug.Methods Self-emulsifying drug delivery systems (SEDDS) were formulated to increase the solubility and ultimately the oral bioavailability of ACF. Oleic acid was used as an oil phase, Tween 80 (T80) and Kolliphor EL (KEL) were used as surfactants, whereas, polyethylene glycol 400 (PEG 400) and propylene glycol (PG) were employed as co-surfactants. Optimized formulations (F1, F2, F3 and F4) were analyzed for droplet size, poly dispersity index (PDI), cell viability studies, in vitro dissolution in both simulated gastric fluid and simulated intestinal fluid, ex vivo permeation studies and thermodynamic stability.Results The optimized formulations showed mean droplet sizes in the range of 111.3 ± 3.2 nm and 470.9 ± 12.52 nm, PDI from 244.6 nm to 389.4 ± 6.51 and zeta-potential from −33 ± 4.86 mV to −38.5 ± 5.15 mV. Cell viability studies support the safety profile of all formulations for oral administration. The in vitro dissolution studies and ex vivo permeation analysis revealed significantly improved drug release ranging from 95.68 ± 0.02% to 98.15 ± 0.71% when compared with control. The thermodynamic stability studies confirmed that all formulations remain active and stable for a longer period.Conclusion In conclusion, development of oral SEDDS might be a promising tool to improve the dissolution of BCS class-II drugs along with significantly reduced exposure to gastric mucosa.
研究领域:
药剂学
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药物化学
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胃肠病学
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DOI
高影响因子
INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
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2024
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IF 3.8
Longping Jiang,Mengmeng Wang,Wenqian Chen,Limin Zhou,Li Xu,Hamza Shehzad,Jinbo Ouyang
Aceclofenac (ACF) is a kind of antipyretic, analgesic, and antiarthritic drug, which is clinically suitable for the treatment of rheumatoid arthritis. However, the morphology of ACF produced in the crystallization process is easily regulated by different solvents, which has a significant effect on the powder properties of the ACF crystals. Therefore, the study of crystal habits is needed for producing ACF with a better performance. In this study, the effects of different solvents on the growth of the ACF crystal were studied by analyzing the morphology of ACF in various solvents and comprehensive simulation calculations. It was found that the ACF crystals in ethanol (EAL) and acetonitrile (ACE) were quadrangular in shape. In methyl acetate (MA), acetone (ACT), and n-propanol (NPL), the lateral aspect of the (101̅) facet is clearly prominent. More interestingly, pentagonal crystals are found only in methanol (MEL), and the (002) facet eventually disappears as they grow. Through molecular dynamics simulations, we have found that the attachment energy Eatt of crystal facets, the Connolly surface coefficient R, and solvent effects Es are the main factors influencing the growth of ACF crystals. The competitive adsorption of ACF and solvent molecules onto crystal facets accounts for morphology change during the growth process. By establishing a strong link between experimental observations and simulation results, this study favors the morphology control of the ACF crystal.
研究领域:
药物化学
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晶体学
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计算化学
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DOI
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
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2026
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IF 4.7
Chenyu Wu,Chang Zhang,Chuxin Liao,Lin Lyv,Lingyun Chen,Fengfeng Wang,Zhengzheng Zhou
Polymorphic cocrystallization substantially enhances the solubility of aceclofenac, a BCS Class II non-steroidal anti-inflammatory drug with poor aqueous solubility. Three novel cocrystals, including aceclofenac-isonicotinamide form I (2:1, ACE-ISO I), aceclofenac-isonicotinamide form II (1:1, ACE-ISO II), and aceclofenac-ethenzamide (1:1, ACE-ETH), were synthesized and characterized by X-ray diffraction, thermal analysis, and spectroscopy to confirm their distinct crystalline structures and phase purity. ACE-ISO II cannot be obtained as a high purity sample due to thermodynamic instability, thus comprehensive physicochemical property evaluation was not performed. Equilibrium solubility tests showed aceclofenac solubilities of 0.116 ± 0.001 μg/mL (pH 1.2), 29.717 ± 0.393 μg/mL (water), and 1260.055 ± 53.970 μg/mL (pH 6.8). In contrast, ACE-ISO I exhibited solubilities of 0.203 ± 0.003 μg/mL, 408.236 ± 9.877 μg/mL, and 1443.445 ± 22.178 μg/mL, while ACE-ETH showed 0.673 ± 0.019 μg/mL, 40.626 ± 0.526 μg/mL, and 2227.213 ± 71.773 μg/mL, respectively. Thermodynamic solubility measurements confirmed ACE-ISO I’s marked improvement, with values of 630.967 ± 5.778 μg/mL (pH 1.2), 3171.085 ± 63.309 μg/mL (water), and 7736.409 ± 415.720 μg/mL (pH 6.8), while ACE-ETH showed moderate enhancements. Both cocrystals displayed pH-dependent solubility behavior. Intrinsic dissolution rate tests highlighted ACE-ISO I’s superior performance (39.83 ± 0.17 μg/cm²/min) compared to aceclofenac (16.63 ± 0.06 μg/cm²/min) and ACE-ETH (31.55 ± 0.13 μg/cm²/min). The substantial solubility and dissolution improvements of ACE-ISO I, driven by strong intermolecular interactions and polymorphic stability, position it as a promising candidate for optimizing aceclofenac formulations in pharmaceutical development.
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产品关联
DOI
高影响因子
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