CHINESE JOURNAL OF CHEMICAL ENGINEERING
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2023
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IF 3.8
Kai Ge,Yiping Huang,Yuanhui Ji
The high throughput prediction of the thermodynamic phase behavior of active pharmaceutical ingredients (APIs) with pharmaceutically relevant excipients remains a major scientific challenge in the screening of pharmaceutical formulations. In this work, a developed machine learning model efficiently predicts the solubility of APIs in polymers by learning the phase equilibrium principle and using a few molecular descriptors. Under the few-shot learning framework, thermodynamic theory (Perturbed-Chain Statistical Associating Fluid Theory, PC-SAFT) was employed for data augmentation, and computational chemistry was applied for molecular descriptors screening. The results showed that the developed machine learning model can predict the API-polymer phase diagram accurately, broaden the solubility data of APIs in polymers, and reproduce the relationship between API solubility and the interaction mechanisms between API and polymer successfully, which provided efficient guidance for the development of pharmaceutical formulations.
研究领域:
药学
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化学工程
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材料科学
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计算化学
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机器学习
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DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2024
·
IF 4.4
Li Shuyu,Hao Hongxun,Wu Di,Yu Hui,Zhao Hongtu,Wu Wenbo,Huang Xin,Wang Na,Zhou Lina,Wang Ting
In-situ API crystallization in carrier matrices has attracted extensive attention in recent years for its advantages over traditional preparation processes. However, due to the lack of systemic research on molecular self-assembly behaviors, the products obtained by in-situ crystallization suffer from the problems of polymorphic transformation and drug expulsion during storage, limiting its industrial application. This paper investigates the in-situ sequential crystallization behavior of tristearin (SSS) and fenofibrate (FEN), utilizing SSS as the carrier and FEN as the API. It was found that the behavior of mixed crystallization significantly differs from single-component crystallization, including direct formation of stable form of SSS and the rapid crystallization of FEN. During the crystallization process , the melting FEN promotes the movement of SSS molecules, while the sliding of SSS lamellae, in turn, provides a mechanical stimulus to enhance the nucleation of FEN. Based on the observed synergistic crystallization behavior, the distribution and stability of the API within FEN solid lipid microparticles (SLMs) during storage were evaluated, while also examining the stability variations in SLMs formulated at different cooling rates and drug loading concentrations. The findings indicate that the initial nucleated FEN results in a decrease in the surrounding molten FEN and the irregularity of the SSS lamellas, thereby preventing the remaining molten FEN from achieving complete crystallization within a brief period. Due to the compatibility between FEN and SSS, some SSS may blend with the molten FEN, potentially resulting in further crystallization during storage and consequently increasing the risk of drug expulsion.
研究领域:
药学
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材料科学
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化学
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DOI
PubMed
高影响因子
Current Pharmaceutical Analysis
·
2023
·Vol. 19
·期 6
·511-520
·
IF 0.6
Zhang Mengmeng,Zou Qiaogen
Background: Atopic dermatitis (AD) is an allergic skin disease that can be inherited. Crisaborole is a specific drug developed to deal with this disease. The compounds of 4-(4- Bromo-3-formyl-phenoxy)-benzonitrile and 4-(4-(4-bromo-3-formylphenoxy)-3- formylphenoxy) benzonitrile
are the representative impurities in the synthesis of Crisaborole active pharmaceutical in gradient (API). Owing to the genotoxic impurities that could lead to cancer and gene mutations, it is necessary to develop a simple, efficient, sensitive, and accurate method to detect these impurities.
In this study, the 4-(4-Bromo-3-formyl-phenoxy)-benzonitrile and 4-(4-(4- bromo-3-formylphenoxy)-3-formylphenoxy)benzo- nitrile present in Crisaborole API were detected using UPLC-MS/MS. Methods: The separation was made on a ZORBAX Eclipse XDB-Pheny column (4.6 mm ×75mm, 3.5
μm) with the mobile phase of acetonitrile solution containing 0.1% trifluoroacetic acid (A) and water containing 0.1% formic acid (B) in gradient elution mode. Quantification was performed using positive ion electrospray ionization (ESI), and the contents of two compounds were determined
using the multiple reaction monitoring (MRM) modes. Results: The quantitative analytical method was fully validated with respect to linearity (r > 0.9998), sensitivity, precision, accuracy (the average recovery of two impurities was 84.1% to 90.7%), and robustness. Conclusion:
Three batches of samples were detected by UPLC-MS/MS, indicating that the proposed approach was applicable for the quality evaluation of Crisaborole.
研究领域:
药物分析
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皮肤病学
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毒理学
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DOI
高影响因子
Biomaterials Advances
·
2026
·
IF 6.7
Wenhao Gao,Bingkun Kang,Shiting Xu,Da Zheng,Shuang Lin,Zhihong Liu,Qian Zhang,Hongtao Song
Disrupting intracellular redox homeostasis may modulate the release of molecular patterns associated with tumor damage, contributing to promoting immunogenic cell death (ICD) for immunotherapy. However, tumors typically exhibit an immunosuppressive microenvironment, which can impede the activation of ICD, thereby enabling immune evasion. In this work, without any excipients and carriers, the full active pharmaceutical ingredient (API) nanoparticles (FeV FANPs) are prepared by the assembly of verteporfin (VER) and iron ions (Fe III ) without any carriers, which possess commendable stability and biocompatibility. Intravenously administered FeV FANPs demonstrate rapid binding to endogenous albumin, facilitating prolonged circulation times in the blood and efficient accumulation within tumor tissues through albumin-assisted targeting mechanisms. Subsequently, FeV FANPs exhibit a GSH-responsive release of VER and Fe III , resulting in Fe III -triggered GSH depletion and VER-mediated photodynamic therapy (PDT), which collectively induce intracellular redox imbalances and ferroptosis in tumor cells, thus promoting ICD. FeV FANPs show significant inhibition of both orthotopic and metastatic tumor growth through PDT-amplified immunotherapy, contributing to the advancement of clinically transferable nanoparticles for tumor immunotherapy.
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PubMed
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-14
·
IF 16.6
Fang Fang,Wang Sa,Song Yueyue,Sun Meng,Chen Wen-Cheng,Zhao Dongxu,Zhang Jinfeng
Nanomedicine holds great promise to enhance cancer therapy. However, low active pharmaceutical ingredient (API) loading content, unpredictable drug release, and potential toxicity from excipients limit their translational capability. We herein report a full-API nanodrug composed of FDA-approved 5-aminolevulinic acid (ALA), human essential element Fe 3+ , and natural bioactive compound curcumin with an ideal API content and pH-responsive release profile for continuous spatiotemporal cancer therapy achieved by multi-step tandem endogenous biosynthesis. First, ALA enzymatically converts into photosensitizer protoporphyrin IX (PpIX). Afterward, multiple downstream products including carbon monoxide (CO), Fe 2+ , biliverdin (BV), and bilirubin (BR) are individually biosynthesized through the PpIX-heme-CO/Fe 2+ /BV-BR metabolic pathway, further cooperating with released Fe 3+ and curcumin, ultimately eliciting mitochondria damage, membrane disruption, and intracytoplasmic injury. This work not only provides a paradigm for exploiting diversified metabolites for tumor suppression, but also presents a safe and efficient full-API nanodrug, facilitating the practical translation of nanodrugs.
研究领域:
纳米医学
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癌症研究
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药学
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生物医学工程
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PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2024
·
IF 9.4
Zhijie Yuan,Lingfeng Wang,Mengyuan Wu,Yuchao Niu,Yingshuang Meng,Xuehua Ruan,Gaohong He,Xiaobin Jiang
Active pharmaceutical ingredients (APIs) crystal preparation is a significant issue for the pharmaceutical development attributed to the effect on anti-inflammatory, anti-bacteria, and anti-viral, etc. While, the massive preparation of API crystal with high polymorphism selectivity is still a pendent challenge. Here, we firstly proposed a criterion according to the molecular aggregation, molecular orientation, and hydrogen bond energy between INA molecules from molecular dynamics (MD) simulations, which predicted the hydrogen bond architecture in crystal under different electric fields, hinting the recognition of crystal polymorphism. Then, an electric field governing confined liquid crystallization was constructed to achieve the INA crystal polymorphism screening relying on the criterion. Further, magnifying confined liquid volume by 5000 times from 1.0 μL to 5.0 mL realized the massive preparation of INA crystal with high polymorphic purity (>98.4%), giving a unique pathway for crystal engineering and pharmaceutical industry on the development of innovative and generic API based drugs.
研究领域:
药学
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材料科学
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计算化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
·
2026
·Vol. 115
·期 11
·104488
·
IF 3.9
Yushan Cheng,Hong Shu,Yingjun Zhang,Lina Qin,Rong Chen,Zhenyu Wang
Determining the particle size distribution (PSD) of the active pharmaceutical ingredient (API) in nasal spray suspensions is a challenging task that usually requires the use of morphologically-directed Raman spectroscopy (MDRS). A dissolution-based modeling strategy was established to characterize the entire PSD of starting API in mometasone furoate nasal sprays using dissolution data of finished formulations, whereas MDRS measures API PSD in the final products. A dissolution-PSD model was built in-house to derive the API PSD from the dissolution data of target products, with model parameters estimated using test products with known raw API PSD and dissolution profiles. To obtain representative dissolution data that could better reflect the intrinsic API PSD characteristics of the formulation, different sample pretreatment procedures and dissolution approaches were investigated. The results suggested that the dissolution profile acquired by the paddle method following combined enzymatic hydrolysis and ultrasonication pretreatment was preferable for characterizing the starting API particle size features. Model predictions demonstrated that the commercial Nasonex® displayed a bimodal volume-weighted PSD and a relatively high Dv 90 of 15.8 μm, which differed from previous reports. A modified MDRS was applied for cross-checking, and the modeled Dv 90 was in agreement with the measured results. Cross-validation for the model using five test batches yielded prediction errors mostly <10%, indicating acceptable performance. For nasal suspension products that typically present complex PSD features, the present method may provide a feasible auxiliary tool for guiding formulation screening and optimizing manufacturing parameters in the preliminary development stage.
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JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 6.8
Wenchen Pu,Xianyan Shen,Xin Fan,Yuanyuan Zheng,Xuesha Liu,Jiao Li,Jian-Kang Zhou,Juan He,Rong Wei,Yanqiu Gong,Qingquan Zheng,Yao Luo,Yingli Guo,Min Ai,Yue Ming,Zixia Ye,Yun Zhao,Chun Wang,Yong Peng
Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths globally, and the need for effective systemic therapies for HCC is urgent. Our previous work reveals that Pin1 is a potential anti-HCC target, which regulates miRNA biogenesis and identifies API-1 as a novel Pin1 inhibitor to suppresses HCC. However, a great demand in HCC therapy as well as the limited chemical stability and pharmacokinetic feature of API-1 motivated us to find improved Pin1 inhibitors. Herein, we designed and synthesized diverse 6-O-benzylguanine derivatives and discovered API-32 as a novel Pin1 inhibitor with better stability and pharmacokinetic property over API-1. API-32 directly interacted with the Pin1 PPIase domain to inhibit Pin1 activity. API-32 significantly suppressed the cell proliferation and migration of HCC cells by blocking Pin1’s downstream signal. Moreover, API-32 exhibited an enhanced inhibitory function against the HCC tumor in mice models without obvious toxicity, making it a promising drug candidate for HCC treatment.
研究领域:
肿瘤学
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药理学
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分子生物学
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PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Chen Chen,Xinlu Li,Weixia Zhu,Yu Chen,Jie Tang,Shun Yao
This study aimed to develop a new suppository containing the complex of active pharmaceutical ingredient-ionic liquid (API-IL) and metal organic framework. As two famous drugs with anti-virus activities for the combination therapy of COVID-19, mefloquine (MQ) hydrochloride and artesunate (Art) were combined and then transformed to API-ILs to enhance therapeutic effects. The synthesized [MQ][Art] was characterized using melting point tests, Fourier transform infrared spectrum (FT-IR), proton nuclear magnetic resonance ( 1 H NMR), and mass spectroscopy (MS). Furthermore, [MQ][Art] exhibited improved water solubility, stability and pH values, which promoted treatment effectiveness while minimizing intestinal irritation during administration. Subsequently, [MQ][Art] was incorporated into Zeolitic imidazolate framework-8 (ZIF-8) to further enhance stability and achieve a controlled release effect. Combined with computational studies on interactive energy between ZIF-8 and API-IL, comprehensive characterizations confirmed the successful incorporation of [MQ][Art] on ZIF-8. The preparation method of suppositories was then investigated; among the 9 tested suppository bases, poloxamer-based suppositories demonstrated uniform quality with suitable hardness and melting time while also exhibiting a controlled release effect on [MQ][Art]. After 10 h of cumulative release rate testing reached 90 %. Finally, the poloxamer-based suppository containing [MQ][Art]@ZIF-8 showed good quality uniformity with an average drug content of 11.4 mg per suppository and an average displacement value of 2.59. Besides that, the in vivo release process was detected to demonstrate the effectiveness of the developed system. In conclusion, the combination of API-ILs with ZIF-8 in suppositories designed for COVID-19 treatment enhances therapy effectiveness by improving solubility and stability while also providing controlled release effects on MQ and Art.
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SCIENCE OF THE TOTAL ENVIRONMENT
·
2022
·
IF 10.753
Sathish Sundararaman,J. Aravind Kumar,Prabu Deivasigamani,Yuvarajan Devarajan
Water is one of the important gifts to mankind. In recent days the accessibility of pharmaceuticals in the environment is progressively a worldwide concern. The significant wellspring of these contaminations in water assets is drugs for human use or veterinary medications. Intermediates, active metabolites and raw materials present in water from pharmaceutical industry waste because of incomplete sewage treatment systems . Various pharmaceutical components such as analgesic/antipyretics such as Ibuprofen (57.9–104 ng/L), Diclofenac (17–129 ng/L), antibiotics such as Sulfamethoxazole (28.7–124.5 ng/L), Sulfamethazine (29.2–83.9 ng/L), Azithromycin (10–68 ng/L), psychiatric drug such as Carbamazepine (9.3–92.4 ng/L), stimulants such as caffeine greater than 55 ng/L, antidepressants, antihypertensive, contraceptives etc., are present in water resources and have been detected in mg/L to μg/L range. The synergic effects and ecotoxicological hazard assessment must be developed. Studies demonstrate that these drugs might cause morphological, metabolic and sex alterations on sea-going species, and interruption of biodegradation activities. Hazard analysis and assessments are in progress. However, the conventional effluent treatment methods are not sufficient to remove API (active pharmaceutical ingredients) from this water effectively. There is necessitate for continuous monitoring of the pharmaceutical compounds in aquatic ecosystem to save the environment and living form of lives from health hazards. This work highlights the hazards, environmental assessment and the mitigation measures of pharmaceutical pollutants.
研究领域:
环境科学
·
水资源管理
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毒理学
·
药学
·
生态学
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DOI
PubMed
高影响因子
Frontiers in Chemistry
·
2020
·
IF 3.693
Li He,Lv Kaihe,Huang Xianbin,Lu Zhen,Dong Xiaodong
Nanoscale plugging agent is essential to wellbore stability of troublesome shale formation in the drilling of oil and gas wells. In this paper, polymeric nanospheres (PNS) with a double cross-linked structure were synthesized using monomers of styrene (ST), acrylamide (AM), 2-Acrylamide- 2-methylpropanesulfonic acid (AMPS), and dimethyl diallyl ammonium chloride (DMDAAC). PNS were characterized by FTIR, SEM and TGA. The plugging performance of PNS was analyzed using nitrogen adsorption experiments and SEM. And compatibility with water based drilling fluid (WBM) was studied. Experimental results showed that PNS had a mean particle size of 133 nm, and could retain about half of the original size after high temperature treatment under 150–200°C. TGA showed that the initial decomposition temperature of PNS is around 315°C. After plugging by PNS, both the specific surface area and pore volume of the shale cuttings decreased substantially compared with those of shale samples treated with water. Thus, PNS was thermal stable in WBM under high temperature and could effectively plug shale pores. Besides, PNS was beneficial to reduce both API and HTHP fluid loss of WBM.
研究领域:
材料科学
·
化学工程
·
石油工程
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2021
·
IF 4.539
Ming Lei,Weian Huang,Jinsheng Sun,Zixuan Shao,Yong Ouyang,Qiaorong Han
Developing drilling fluid materials from modified biomass to meet drilling and environmental requirements has always been of concern. This paper reports for the first time the use of polyampholyte hydrophobically modified by epoxidized soybean oil (ESO), as a potential shale inhibitor. It (AADE) was prepared by micellar polymerization of acrylamide (AM), 2-acrylamide-2-methylpropanesulfonic acid (AMPS) and methacrylatoethyl trimethyl ammonium chloride (DMC) with pre-prepared ESO-derived methacrylate monomer (ESO-MA). Its molecular structure was confirmed by Fourier transform infrared spectroscopy and proton nuclear magnetic resonance . A comparative study of obtained AADE and the polyampholyte without hydrophobic modification (AAD) was carried out through thermal properties , rheological properties, inhibition performance and drilling fluid compatibility tests. The results showed that AADE possessed higher thermal stability due to the presence of hydrophobic associative ability and crosslinkable epoxy groups , and the hydrophobic interaction between AADE chains dominated the shear-thinning behavior and lowered the viscosity-temperature and viscosity-salt dependence. Also, AADE at a lower concentration more effectively prevented clay hydration swelling and inhibited shale disintegration than AAD and conventional inhibitors. Meanwhile, AADE was well compatible with bentonite dispersion in both fresh water and brine, and improved rheological properties and decreased API and high temperature high pressure (HTHP) fluid loss before and after hot rolling. The inhibition mechanism of AADE was revealed to be the synergetic actions of physical plugging of hydrophobic associated multipolymer aggregates in micro-pores of shale, chemical film with a hydrophobic shell formed on clay surface, and the surface activity to reduce capillary driven force. This research might provide an insight for the application of hydrophobically modified polymer, particularly plant oil-based, as shale inhibitor in water-based drilling fluid.
研究领域:
材料科学
·
化学工程
·
石油工程
·
环境科学
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DOI
高影响因子
危险品化学品经营许可证（带存储）