JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2023
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IF 3.4
Ling Bai,Yanlan Zhang,Cai Zhang,Yuchen Lu,Zhiguo Li,Gang Huang,Bo Meng
A study on the polysorbate 80 stability in various formulation buffers commonly used in biopharmaceuticals was performed, to investigate the excipients influence on polysorbate 80 degradation. Polysorbate 80 is a common excipient in biopharmaceutical products. However, its degradation will potentially impact the drug product quality, and may trigger protein aggregation and particles formation. Due to the heterogeneity of the polysorbates and the mutual effects with other formulation compositions , the study of polysorbate degradation is challenging. Herein, a real-time stability study was designed and performed. The polysorbate 80 degradation trend was monitored by fluorescence micelle-based assay (FMA), reversed-phase-ultra-performance liquid chromatography-evaporative light scattering detector (RP-UPLC-ELSD) assay, and LC-MS assay. These assays provide orthogonal results to reveal both the micelle-forming capability and the compositional changes of polysorbate 80 in different buffer systems. The degradation occurred after a period of storage under 25 °C in different trend, which indicates the excipients could impact the degradation kinetics. Upon comparison, the degradation is prone to happen in histidine buffer than in acetate, phosphate or citrate buffers. LC-MS confirms oxidation as an independent degradation pathway with detection of the oxidative aldehyde. Thus, it is necessary to pay more attention to the excipients selection and their potential impact on polysorbate 80 stability to achieve longer shelf life for the biopharmaceuticals. Besides, the protective roles of several additives were figured out, which could be applied as potential industrial solutions to the polysorbate 80 degradation issues.
研究领域:
生物制药
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药物化学
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产品关联
DOI
PubMed
高影响因子
Pharmaceutics
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2025
·Vol. 17
·期 12
·1543
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IF 5.5
Han Gao,Jun Ouyang,Zhi-Bo Hu,Wei-Jie Fang
Background : Despite the growing importance of polypeptide-based drugs in clinical therapy, studies investigating the stability of their freeze-dried formulations remain scarce. Crystalline excipients, such as mannitol, are commonly used in freeze-dried formulations of chemically synthesized drugs, but they often negatively impact the long-term stability of biological macromolecules like monoclonal antibodies (mAbs). This study bridges this knowledge gap by evaluating the effects of crystalline and amorphous excipients, surfactants, and amino acid-based stabilizers on the long-term stability of freeze-dried formulations using model polypeptides, glucagon and insulin. Methods : The freeze-dried formulations were prepared with crystalline and amorphous excipients, surfactants, and amino acid-based stabilizers. The crystallization behavior of the excipients and the thermal stability of the formulations were thoroughly characterized using X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC). Results : The crystallization of mannitol was directly correlated with a significant reduction in the long-term stability of both model polypeptides. This detrimental effect mirrors the instability observed in mAbs formulations, indicating a common mechanism of protein destabilization induced by crystalline excipients, independent of molecular size. Conclusions : This study provides the first direct evidence that crystalline excipients pose a significant risk to the stability of freeze-dried polypeptides. These findings offer critical insights for the rational design of stable freeze-dried formulations, guiding industrial development strategies for polypeptide-based therapeutics.
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2016
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IF 2.857
Xing Chen,Liqiang Zou,Wei Liu,David Julian McClements
The potential for excipient emulsions to enhance the bioaccessibility and antioxidant activity of quercetin was determined in this study. Oil-in-water excipient emulsions containing two levels (4 or 10%) of small lipid droplets (d < 250 nm) were prepared from a long-chain triglyceride (corn oil). The solubilization of quercetin by the excipient emulsions was faster than by bulk corn oil or bulk water, and the solubilization rate was higher at 100 °C than at 30 °C. The bioaccessibility of quercetin samples was determined using an in vitro gastrointestinal model, and the bioactivity of quercetin was determined using a rat feeding study. The excipient emulsions were more effective at enhancing quercetin bioaccessibility and rat plasma antioxidant activity than either bulk oil or bulk water. This effect was attributed to the rapid digestion of the long chain triglycerides when they were in an emulsified form, which led to the rapid production of mixed micelles capable of solubilizing, protecting, and transporting quercetin.
研究领域:
药剂学
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营养保健品
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食品科学
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生物药剂学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Lu Zhang,Yanxia Zhou,Xinyu Chai,Zhenzhen Yang,Ning Pang,Yitian Du,Xianrong Qi
This study reports the design of a novel excipient-free small molecule prodrug (DEX-ALA)-based nanoparticle (DEX-ALA/DTX) which combines (i) the ability to target dexamethasone (DEX) and docetaxel (DTX) simultaneously to an experimental solid tumor under the natural tumor-targeting properties with (ii) high drugs loading (49.3% DTX, 29.2% DEX, and 21.5% ALA), (iii) high stability (low premature release) in circulation, (iv) stimuli responsive disassembly and release DEX and DTX in tumor, and inducing immunogenic cell death (ICD) for immunotherapy. This concept is based on the inclusion of hydrophobic DTX into nanoparticles constructed by self-assembling of esterase-responsive prodrug of α-linolenic acid (ALA) dexamethasone conjugate. Computational and experimental evidences prove the recapitulation of nanoparticles structure and esterase-responsive release. In tumor compartment, DEX modulates tumor microenvironment, reduces interstitial fluid pressure (IFP) to promote DEX-ALA/DTX nanoparticles accumulating in tumor, and also suppresses inflammation induced tumor progression. DTX exerts its cytotoxicity effect to eliminate tumor cells and induces ICD to produce antitumor immune response. Both systemic administration and peritumoral administration of DEX-ALA/DTX nanoparticles display excellent tumor shrinkage on 4 T1 breast cancer models, but the histology investigation of the tumor biopsies evidences lung metastasis of peritumoral route. These findings give insight in overcoming tumor microenvironment obstacles to promote nanoparticles accumulation and provide a rational strategy to increase antitumor efficiency. This new excipient-free small molecule prodrug based nanotechnology platform is expected to have important applications in cancer therapy.
研究领域:
纳米技术
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癌症治疗
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药学
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免疫疗法
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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）