AAPS PHARMSCITECH
·
2025
·Vol. 26
·期 7
·1-17
·
IF 4
Tan Lihua,Jing Zhongli,Li Na,Yu Xuan,Liu Yi,Wang Meng,Ren Xiaoliang
This study introduced a novel vectorized Biopharmaceutics Classification System (BCS) model designed to evaluate the biopharmaceutical properties of active pharmaceutical ingredients (APIs) and their variations under different influencing factors. The model was validated using water-soluble supramolecular p -Sulfonatocalix[n]arenes (SCnA, n = 6, 8), promising pharmaceutical adjuvants, to enhance the solubility and bioavailability of a series of APIs in vitro . The binding interactions of SCnA with 22 alkaloids were assessed for their impact on solubility and permeability using the classical shake-flask method and the parallel artificial membrane permeability assay (PAMPA). To quantify the effects, the change in directional cosine (θ) for each API was calculated by measuring the ratio of the differences in x- and y-coordinates before and after binding. The linear distance and modulus length (r) changes for each API were determined using the Pythagorean theorem, enabling a quantitative assessment of the modifications in solubility and permeability. The potential changes in oral bioavailability pre- and post-binding were visualized using heat maps based on θ and r, highlighting significant improvements in the solubility of compounds such as allicin, tetrandrine, lycorisine, and others. These changes corresponded with shifts in BCS classification, indicating a positive relationship between SCnA concentration, cavity size, and enhanced solubility. The study also evaluated the influence of pH, and concentrations of host and guest, to assess the tolerance of SCnA for further pharmaceutical applications. Based on prior safety assessments, SCnA ( n = 6, 8) demonstrated significant potential as solubilizing excipients. The vectorized BCS model enabled precise, quantitative analysis of biopharmaceutical property variations without added experimental complexity, offering a tool for high-throughput screening of excipients in pharmaceutical formulation and processing. Graphical
研究领域:
药剂学
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药物递送
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生物药剂学
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超分子化学
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药用辅料
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体外研究
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产品关联
DOI
PubMed
高影响因子
Heliyon
·
2023
·
IF 4
Yongfeng Zhao,Ying Fan,Yan Zhang,Hong Xu,Min Li,Yunjie Zhu,Zhao Yang
According to crystal engineering, the pharmaceutical intermediate m -nitrobenzoic acid (MNBA), which contains a carboxylic acid group, was selected as a coformer (CCF) for drug cocrystallization with famotidine (FMT), and a new stable FMT salt cocrystal was synthesized. The salt cocrystals were characterized by scanning electron microscopy, differential scanning calorimetry, thermogravimetric analysis, infrared spectroscopy, powder X-ray diffraction and X-ray single crystal diffraction. A single crystal structure of FMT–MNBA (1:1) was successfully obtained, and then the solubility and permeability of the newly synthesized salt cocrystal were studied. The results showed that, compared with free FMT, the FMT from the FMT–MNBA cocrystal showed improved permeability. This study provides a synthetic method to improve the permeability of BCS III drugs, which will contribute to the development of low-permeability drugs.
研究领域:
药学
·
晶体工程
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DOI
高影响因子
Pharmaceutics
·
2023
·Vol. 15
·期 5
·1341
·
IF 5.4
Yuze Sheng,Qin Yu,Yanping Huang,Quangang Zhu,Zhongjian Chen,Wei Wu,Tao Yi,Yi Lu
Nanocrystals (NCs) have the potential to enhance the oral bioavailability of Class IV drugs in the Biopharmaceutical Classification System (BCS) due to the absorption of the intact crystals. The performance is compromised by the dissolution of NCs. Drug NCs have recently been adopted as solid emulsifiers to prepare nanocrystal self-stabilized Pickering emulsions (NCSSPEs). They are advantageous in high drug loading and low side effects due to the specific drug loading mode and the absence of chemical surfactants. More importantly, NCSSPEs may further enhance the oral bioavailability of drug NCs by impeding their dissolution. This is especially true for BCS IV drugs. In this study, curcumin (CUR), a typical BCS IV drug, was adopted to prepare CUR-NCs stabilized Pickering emulsions using either indigestible (isopropyl palmitate, IPP) or digestible (soybean oil, SO) oils, i.e., IPP-PEs and SO-PEs. The optimized formulations were spheric with CUR-NCs adsorbed on the water/oil interface. The CUR concentration in the formulation reached 20 mg/mL, which was far beyond the solubility of CUR in IPP (158.06 ± 3.44 μg/g) or SO (124.19 ± 2.40 μg/g). Moreover, the Pickering emulsions enhanced the oral bioavailability of CUR-NCs, being 172.85% for IPP-PEs and 152.07% for SO-PEs. The digestibility of the oil phase affected the amounts of CUR-NCs that remained intact in lipolysis and, thus, the oral bioavailability. In conclusion, converting NCs into Pickering emulsions provides a novel strategy to enhance the oral bioavailability of CUR and BCS IV drugs.Keywords:curcumin;nanocrystals;Pickering emulsions;oral bioavailability;BCS IV;lipolysis
研究领域:
药剂学
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生物医学工程
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药物代谢
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DOI
PubMed
高影响因子
Pharmaceuticals
·
2024
·Vol. 17
·期 4
·412
·
IF 4.3
Zicheng Zhong,Yanling Lan,Jinxing Chen,Lu Ping,Xuchun Li,Qing Wang,Xiaodong Zhuang,Zhenwen Qiu,Tianhui Yuan,Qiupin Guo,Long Xi,Qingguo Li,Dandong Luo
Supercritical anti-solvent fluidized bed (SAS-FB) coating technology has the advantages of reducing particle size, preventing high surface energy particle aggregation, improving the dissolution performance and bioavailability of insoluble drugs. The poor solubility of Biopharmaceutics Classification System (BCS) class IV drugs poses challenges in achieving optimal bioavailability. Numerous anti-cancer drugs including paclitaxel (PTX) belong to the BCS class IV, hindering their therapeutic efficacy. To address this concern, our study explored SAS-FB technology to coat PTX with D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) onto lactose. Under our optimized conditions, we achieved a PTX coating efficiency of 96.8%. Further characterization confirmed the crystalline state of PTX in the lactose surface coating by scanning electron microscopy and X-ray powder diffraction. Dissolution studies indicated that SAS-FB processed samples release over 95% of the drug within 1 min. Moreover, cell transmembrane transport assays demonstrated that SAS-FB processed PTX samples co-coated with TPGS had an enhanced PTX internalization into cells and a higher permeability coefficient compared to those without TPGS. Finally, compared to unprocessed PTX, SAS-FB (TPGS) and SAS-FB processed samples showed a 2.66- and 1.49-fold increase in oral bioavailability in vivo, respectively. Our study highlights the efficacy of SAS-FB co-coating for PTX and TPGS as a promising strategy to overcome bioavailability challenges inherent in BCS class IV drugs. Our approach holds broader implications for enhancing the performance of similarly classified medications.
研究领域:
药剂学
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药物递送系统
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生物医学工程
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DOI
PubMed
高影响因子
Pharmaceutics
·
2026
·Vol. 18
·期 8
·1010
·
IF 6.9
Zeyu Wen,Xilu Sun,Sumeng Chen,Jinyan Meng,Runlin Yu,Shuyan Guo,Xingyuan Cao
Background: The Biopharmaceutics Classification System (BCS) classifies drug substances according to their aqueous solubility and intestinal permeability; however, its application to veterinary drugs should account for species-specific gastrointestinal physiology. Grapiprant is a selective prostaglandin E2receptor subtype 4 (EP4) antagonist approved as an oral tablet to control pain and inflammation associated with osteoarthritis in dogs, but its properties within the BCS framework remain unclear.Methods: This study evaluated the equilibrium solubility of grapiprant across pH conditions relevant to the canine gastrointestinal tract and calculated the dose number (D0) based on different gastric fluid volumes. A Caco-2 cell monolayer model was used to assess grapiprant intestinal permeability and the effects of time, concentration, pH, and efflux transporter inhibitors on its transepithelial transport.Results: Grapiprant showed relatively small changes in solubility across the tested pH range. D0varied with pH and gastric fluid volume and approached or fell below 1 at larger fluid volumes. In the Caco-2 model, grapiprant showed generally limited apparent absorptive permeability, with permeability varying with pH. Efflux ratios were greater than 1, and verapamil reduced the efflux ratio, suggesting possible P-glycoprotein (P-gp) involvement.Conclusions: These findings suggest that both solubility and apparent intestinal permeability may limit the oral absorption of grapiprant under certain canine-relevant conditions. Accordingly, this study provides a biopharmaceutical characterization of grapiprant within the BCS framework rather than a definitive canine BCS classification, highlighting the importance of considering canine gastrointestinal conditions when interpreting its solubility and permeability. The results may support future optimization of dosing conditions and oral formulations.
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高影响因子
RENEWABLE ENERGY
·
2024
·
IF 9
Shengyan Wang,Hongyu Fu,Abulikemu Abulizi,Kenji Okitsu,Yasuaki Maeda,Aisha Nulahong,Tiezhen Ren,Shengli Niu
In this study, an environmentally friendly and recyclable acid-base bifunctional CaO-SrO/biomass chars (BCs) catalyst was prepared using egg shells and poplar leaves as the base materials, and it was used to transesterify waste sheep fat into biodiesel. The structure and properties of the catalysts were investigated by EDX/SEM, BET, NH 3 TPD, and XRD analyses. Biodiesel yield was optimized for maximum values using RSM and ANN. The highest biodiesel yield of 98.83 % was achieved at a catalyst amount of 6 wt%, an alcohol-oil ratio of 8:1, a reaction time of 1.5 h, and a reaction temperature of 65 °C. The catalyst maintained 80.3 % yield after five cycles and showed good acid resistance. By studying the thermodynamics and kinetics behavior of transesterification, the results showed that the doping of SrO reduced the activation energy of the reaction, the activation energy of the reaction is 45.38 kJ/mol. These results show the great potential of our catalyst in transesterification reactions. In addition, the quality of sheep fat biodiesel meets the ASTM D6751 standard. In a life cycle cost analysis, it is shown that our process is relevant for the scale-up and to industrialize of biodiesel production.
研究领域:
能源与环境科学
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催化化学
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生物技术
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DOI
高影响因子
Chinese Physics B
·
2022
·Vol. 31
·期 3
·037406
·
IF 1.652
Dong Yan,Lingyong Zeng,Yijie Zeng,Yishi Lin,Junjie Yin,Meng Wang,Yihua Wang,Daoxin Yao,Huixia Luo
The relationship between charge-density-wave (CDW) and superconductivity (SC), two vital physical phases in condensed matter physics, has always been the focus of scientists' research over the past decades. Motivated by this research hotspot, we systematically studied the physical properties of the layered telluride chalcogenide superconductors CuIr2−xAlxTe4 (0 ⩽ x ⩽ 0.2). Through the resistance and magnetization measurements, we found that the CDW order was destroyed by a small amount of Al doping. Meanwhile, the superconducting transition temperature (Tc) kept changing with the change of doping amount and rose towards the maximum value of 2.75 K when x = 0.075. The value of normalized specific heat jump (Δ C/γ Tc) for the highest Tc sample CuIr1.925Al0.075Te4 was 1.53, which was larger than the BCS value of 1.43 and showed the bulk superconducting nature. In order to clearly show the relationship between SC and CDW states, we propose a phase diagram of Tc vs. doping content.
研究领域:
凝聚态物理
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材料科学
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超导性
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电荷密度波
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DOI
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2019
·
IF 2.12
Qiang Fu,Hai-Dong Lu,Yi-Fei Xie,Jia-You Liu,Yang Han,Ning-Bo Gong,Fang Guo
Indomethacin ( Indo ) and naproxen ( Nap ) belong to Biopharmaceutical Classification System (BCS) class II drugs, which permeate membranes well but are poorly soluble. Two pharmaceutical salts hydrate of Indo and Nap with (1R,2R)-1,2-diphenylethylenediamine ( DPEN ) were obtained using solution crystallization. Both salts, (DPEN) 2 ·(Indo) 2 ·(H 2 O) 2 and (DPEN) 1 ·(Nap) 1 ·(H 2 O) 0.5 , were characterised using various solid-state characterisation techniques such as single crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and Raman spectra . The structure analysis shows that DPEN is monocation as only one amine is protonated into ammonium. The Indo , DPEN and water molecules form one-dimensional hydrogen bond chains through extensive N H⋯O, N H⋯N and O H⋯N interactions. The solubility study shows that the two salts are more soluble in pH 1.2, 4.5 and 6.8 buffer mediums compared with pure raw materials. Solubility thermodynamics calculation was carried out to further understand the solubility properties of two salts.
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DOI
高影响因子
Acta Pharmaceutica Sinica B
·
2014
·
IF 0
Huiyi Wu,Xiaoying Long,Fei Yuan,Li Chen,Sujing Pan,Yunjun Liu,Yoshiko Stowell,Xiaoling Li
The aim of this study was to develop a formulation to improve the oral absorption of baicalin (BA) by combining a phospholipid complex (PC) and self-emulsifying microemulsion drug delivery system (SMEDDS), termed BA–PC–SMEDDS. BA–PC was prepared by a solvent evaporation method and evaluated by complexation percentage (CP). The physicochemical properties of BA–PC were determined. The synergistic effect of PC and SMEDDS on permeation of BA was studied in vitro with Caco-2 cells and in situ with a single pass intestinal perfusion model. The improved bioavailability of BA in BA–PC–SMEDDS was confirmed in an in vivo rat model. The CP of BA–PC reached 100% when the molar ratio of drug to phospholipid (PP) was ≥1:1. The solubility of BA–PC increased in both water and octanol, and the log P o/w of BA–PC was increased significantly. BA–PC–SMEDDS could be dispersed more evenly in water, compared to BA and BA–PC. Both the Caco-2 cell uptake and single-pass intestinal perfusion models illustrated that transport of BA in BA–PC was lower than that of free BA, while improved significantly in BA–PC–SMEDDS. The relative bioavailability of BA–PC(1:2)–SMEDDS was 220.37%. The combination system of PC and SMEDDS had a synergistic effect on improving the oral absorption of BA.
研究领域:
药剂学
·
药物代谢动力学
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产品关联
DOI
PubMed
International Journal of Nanomedicine
·
2023
·
IF 8
Jingyi Ye,Huiyi Wu,Chuanli Huang,Wanting Lin,Caifeng Zhang,Bei Huang,Banyi Lu,Hongyu Xu,Xiaoling Li,Xiaoying Long
Purpose The objective of this study was to compare the in vitro Fick’s first law, in vitro lipolysis, and in vivo rat assays for oral absorption of Biopharmaceutical Classification Systems Class II (BCS II) drugs in self-nanoemulsifying drug delivery system (SNEDDS), and studied drugs and oils properties effects on the absorption.Methods The transport abilities of griseofulvin (GRI), phenytoin (PHE), indomethacin (IND), and ketoprofen (KET) in saturated water solutions and SNEDDS were investigated using the in vitro Madin-Darby canine kidney cell model. GRI and cinnarizine (CIN) in medium-chain triglycerides (MCT)-SNEDDS and long-chain triglycerides (LCT)-SNEDDS were administered in the in vivo SD rat and in vitro lipolysis models to compare the oral absorption and the distribution behaviors in GIT and build an in vitro-in vivo correlation (IVIVC).Results In the cell model, the solubility of GRI, PHE, IND, and KET increased 6–8 fold by SNEDDS, but their permeability were only 18%, 4%, 8%, and 33% of those of their saturated water solutions, respectively. However, in vivo absorption of GRI-SNEDDS was twice that of the GRI suspension and those of CIN-SNEDDS were 15–21 fold those of the CIN suspension. In the lipolysis model, the GRI% in aqueous and pellet phases of MCT were similar to that in LCT. In contrast, the CIN% in the aqueous and pellet phases were decreased but that of the lipid phase increased. In addition, an IVIVC was found between the CIN% in the lipid phase and in vivo relative oral bioavailability (Fr).Conclusion The in vitro cell model was still a suitable tool to study drug properties effects on biofilm transport and SNEDDS absorption mechanisms. The in vitro lipolysis model provided superior oral absorption simulation of SNEDDS and helped to build correlation with in vivo rats. The oral drug absorption was affected by drug and oil properties in SNEDDS.
研究领域:
药理学
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药物递送系统
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生物药剂学
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DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2025
·Vol. 26
·期 2
·60
·
IF 4
Zhang Zhaoyang,Wang Sheng,Wang Qianlei,Ye Qian,Wang Wenjuan
Ion pairs represent a robust molecular force arising from the union of oppositely charged ions, held together by Coulomb attraction. Daidzein (Dai), categorized as a BCS IV drug, faces limitations in clinical application due to its relatively low solubility. To enhance the drug’s solubility, a Dai ion pair was prepared, and the mechanism underlying ion-pair formation was investigated. A comprehensive approach, combining experimental techniques and theoretical calculations, such as scanning electron microscopy, powder X-ray diffraction, differential scanning calorimetry, Fourier-transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, X-ray Photoelectron Spectroscopy, and computational simulation was employed to explore the ion-pair formation mechanism. The findings indicate a significant improvement in Dai solubility through the preparation of Arg and Lys ion-pair compounds. The results revealed that the Dai–Lys ion pair exhibited more short hydrogen bonds and fewer long hydrogen bonds than did the Dai–Arg ion pair, strengthening the intermolecular interactions and improving crystal structure stability. This study effectively enhanced the solubility of Dai and offers valuable insights into the mechanisms underlying ion pair formation in ionizable drugs. Graphical
研究领域:
药学
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药物递送
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分子药剂学
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晶体工程
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计算化学
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产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2026
·Vol. 18
·期 6
·634
·
IF 6.9
Yan Lin,Xian Zhang,Fulin Bi,Guangji Wang,Jin Yang
Background/Objectives:Despite the presumption of bioequivalence for BCS Class I drugs due to their high solubility and permeability, recent evidence indicates that those with rapid systemic elimination exhibit heightened vulnerability toCmaxnon-equivalence, primarily attributable to intrasubject variability in gastrointestinal transit and absorption kinetics. It is well known that gastric emptying is a significant physiological-dependent factor. But, does the formulation affect gastric emptying?Methods:Using zidovudine as a model drug, formulations containing sodium carboxymethyl starch (CMS-Na), pregelatinized starch, hydroxypropyl methylcellulose (HPMC), and lactose were investigated for their effects on gastric emptying kinetics, and the impact of excipient-mediated gastric emptying prolongation on pharmacokinetic parameters was also evaluated.Results:Relative to AZT alone (Cmax= 13,350 ng/mL; gastric %ID = 11.3%), co-administration with CMS-Na, pregelatinized starch, or HPMC significantly prolonged gastric retention (%ID: 23.4%, 30.5%, and 40.8% at 22.5 min) and reducedCmaxin rats by 47.8%, 34.4%, and 35.1%, respectively, with no effect on intestinal permeability. Viscosity positively correlated with gastric emptying delay.Conclusions:Our rat findings provide new possible mechanistic evidence that certain viscosity-modifying excipients can delay gastric emptying and reduceCmaxof zidovudine, a rapidly eliminated BCS Class I drug, with potential implications for biowaiver risk assessment. Gastric emptying is not only a physiological-dependent variation but also, in cases where common excipients may significantly delay gastric emptying, a formulation-dependent rate-limiting step. For such drugs, excipient-induced gastric emptying delay poses an underappreciated risk to the biowaiver approach, necessitating more prudent regulatory assessment that encompasses the dynamic interplay among sequential rate processes governing drug disposition.
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DOI
高影响因子
危险品化学品经营许可证（带存储）