Journal of pharmaceutical sciences最新文献_第5页

Correlation of surface properties with dissolution behavior of amorphous solid dispersion of Riluzole and its pharmacodynamic evaluation. 利鲁唑无定形固体分散体表面特性与溶解行为的相关性及其药效学评价

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-15 DOI: 10.1016/j.xphs.2024.10.010

Kanchan Bharti, Abhishek Jha, Manish Kumar, Manjit, Amol Parasram Satpute, Akhilesh, Vinod Tiwari, Brahmeshwar Mishra

{"title":"Correlation of surface properties with dissolution behavior of amorphous solid dispersion of Riluzole and its pharmacodynamic evaluation.","authors":"Kanchan Bharti, Abhishek Jha, Manish Kumar, Manjit, Amol Parasram Satpute, Akhilesh, Vinod Tiwari, Brahmeshwar Mishra","doi":"10.1016/j.xphs.2024.10.010","DOIUrl":"10.1016/j.xphs.2024.10.010","url":null,"abstract":"Formulation of amorphous solid dispersion (ASD) of any poorly water-soluble drug is among the most promising techniques to increase the dissolution profile of drug and hence its bioavailability. Various literatures give evidences of the role of drug-polymer interactions in the ASD systems, very little information is available about the surface properties of the drug molecule and their ASDs which contributes to a higher dissolution profile. Current work focuses on exploring the surface behavior of a poorly water-soluble drug Riluzole (RLZ) and its ASDs prepared with two highly hydrophilic polymers, polyacrylic acid (PAA), and polyvinylpyrrolidone vinyl acetate (PVP VA). Initial characterization using X-ray diffraction (XRD) revealed about the weight fraction of drug required to prepare a single-phase homogenous system with both the polymers. The saturation solubility and the dissolution studies showed an increase in RLZ solubility as well as the dissolution profile due to the presence of polymers. The role of polymers in changing the surface properties in terms of wettability and polarity were explored using contact angle method and X-ray photon spectroscopy (XPS). Additionally, the neuroprotective efficacy and dose dependent hepatotoxicity were also evaluated in male wistar rats. These studies confirmed the increase in the surface polarity and hence the enhanced ability of ASD formulations to interact with water. The in vivo studies indicated that at the current recommended dose the efficacy as well as toxicity is increased for the ASD formulation. Hence, this formulation can be given at a lower dose to achieve same therapeutic effect with lower toxicity.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Novel Cocrystal Approach Celecoxib with Piperine: Simultaneously Enhance Dissolution Rate and Compressibility. 塞来昔布与胡椒碱的新型共晶体方法：同时提高溶出率和可压缩性

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-14 DOI: 10.1016/j.xphs.2024.10.011

Lili Fitriani, Fauziyyah Dirfedli, Yori Yuliandra, Dwi Setyawan, Masaki Uchida, Hironaga Oyama, Hidehiro Uekusa, Erizal Zaini

{"title":"A Novel Cocrystal Approach Celecoxib with Piperine: Simultaneously Enhance Dissolution Rate and Compressibility.","authors":"Lili Fitriani, Fauziyyah Dirfedli, Yori Yuliandra, Dwi Setyawan, Masaki Uchida, Hironaga Oyama, Hidehiro Uekusa, Erizal Zaini","doi":"10.1016/j.xphs.2024.10.011","DOIUrl":"https://doi.org/10.1016/j.xphs.2024.10.011","url":null,"abstract":"Celecoxib, a selective COX-2 inhibitor non-steroidal anti-inflammatory drug (NSAID), exhibits analgesic and anti-inflammatory properties similar to piperine, the secondary metabolite of Piper nigrum L. Unfortunately, celecoxib has a low compressibility and low dissolution rate in aqueous medium. This study aimed to prepare a cocrystal of celecoxib and piperine to enhance the dissolution rate and compressibility properties of celecoxib. The cocrystal was synthesized using the seeding method and thoroughly characterized using Powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), infrared spectrophotometry, and single-crystal X-ray diffraction techniques. The complete change in PXRD, decrease in melting point in DSC measurements, and shift in the N-H stretching band in the FT-IR spectrum suggested the formation of cocrystals phase. Single-crystal XRD confirmed the formation of an equimolar ratio of cocrystals of celecoxib and piperine. The intrinsic dissolution test was conducted to confirm the impact on the cocrystal to dissolution, and it showed a slight increase compared to intact celecoxib. To assess the physico-mechanical properties, the cocrystal powders were compressed into tablets with varying forces. The results demonstrated a significant improvement in compressibility compared with intact celecoxib owing to the slip plane in the crystal lattice of the cocrystal. In conclusion, our novel celecoxib-piperine cocrystal exhibited distinct physicochemical characteristics compared to intact celecoxib, showing enhanced dissolution rate and compressibility.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bioequivalence Requirements for Orally Inhaled and Nasal Drug Products and Use of Novel Physiologically Based Biopharmaceutics Modeling Approaches for Assessing In Vivo Performance. 口服和鼻腔药物产品的生物等效性要求，以及使用基于生理学的新型生物药剂学建模方法评估体内性能。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-14 DOI: 10.1016/j.xphs.2024.10.009

Arvind Rachapally, Rajkumar Boddu, Sivacharan Kollipara, Tausif Ahmed

{"title":"Bioequivalence Requirements for Orally Inhaled and Nasal Drug Products and Use of Novel Physiologically Based Biopharmaceutics Modeling Approaches for Assessing In Vivo Performance.","authors":"Arvind Rachapally, Rajkumar Boddu, Sivacharan Kollipara, Tausif Ahmed","doi":"10.1016/j.xphs.2024.10.009","DOIUrl":"https://doi.org/10.1016/j.xphs.2024.10.009","url":null,"abstract":"Orally inhaled and nasal drug products (OINDPs) are complex due to the interplay between the device, formulation, and patient characteristics. Establishing bioequivalence (BE) of OINDPs with reference is highly complex and require in vitro, in vivo pharmacokinetic and comparative clinical endpoint studies that are challenging to conduct. In order to increase the rate of submission and approval of generics, regulatory agencies are encouraging the use of alternative in vitro and in silico methodologies to replace complex in vivo studies. The present review attempts to summarize current understanding of alternative BE approaches for OINDPs. In vitro characterization studies required for establishing BE for OINDPs considering USFDA and EMA guidance's are detailed. In silico methods such as pulmonary compartmental transit and absorption (PCAT) with emphasis on model input parameters are portrayed. Further, two detailed case studies of inhalation nebulizer and nasal spray formulations are described where PCAT models are developed for predicting BE and local concentrations. Lastly, current understanding of such BE approaches from regulatory perspectives are discussed summarizing recent regulatory workshops and through collation of USFDA product specific guidance's for almost 70 drug products. Overall, this manuscript can act as ready-to-use guide to understand alternative approaches for establishing BE for OINDPs.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Importance of RNase monitoring during large-scale manufacturing and analysis of mRNA-LNP based vaccines. 在大规模生产和分析基于 mRNA-LNP 的疫苗过程中监测 RNase 的重要性。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-14 DOI: 10.1016/j.xphs.2024.10.012

Robbe Van Pottelberge, Roman Matthessen, Shauna Salem, Ben Goffin, Nancee Oien, Pratima Bharti, David Ripley

{"title":"Importance of RNase monitoring during large-scale manufacturing and analysis of mRNA-LNP based vaccines.","authors":"Robbe Van Pottelberge, Roman Matthessen, Shauna Salem, Ben Goffin, Nancee Oien, Pratima Bharti, David Ripley","doi":"10.1016/j.xphs.2024.10.012","DOIUrl":"https://doi.org/10.1016/j.xphs.2024.10.012","url":null,"abstract":"Ribonucleases (RNases) are ubiquitous in nature, being able to cleave a wide range of polyribonucleotides. While the presence of microbial and viral contamination in sterile manufacturing is highly studied and controlled, there are no standardized practices for evaluating RNase in the production facility. Since the COVID-19 pandemic, mRNA-LNP based vaccines have become part of routine large-scale manufacturing. The unstable nature of mRNA poses new challenges to safeguard the working efficacy of mRNA - Lipid nanoparticle (LNP) based vaccines or therapeutics, where the presence of RNase in the formulation process could have a profound impact on the mRNA integrity. In this article, lessons learned are presented with respect to the evaluation of RNase contamination during LNP drug product formulation and analysis. Using sensitive detection methods, the potential presence of RNase in the manufacturing of mRNA-LNPs was investigated. Additionally, capillary gel electrophoresis (CGE) data, used to measure mRNA integrity, demonstrate the quality of the active mRNA substance and importance of suitable RNase control strategies. The results and cases presented in this paper should pave the way forward for evaluation and control strategies dedicated to mRNA-LNP based vaccines and therapeutics.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dissolution of copovidone-based amorphous solid dispersions: Influence of atomic layer coating, hydration kinetics, and formulation. 基于 Copovidone 的无定形固体分散体的溶解：原子层涂层、水合动力学和配方的影响

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-09 DOI: 10.1016/j.xphs.2024.10.001

Emily G Benson, Dana E Moseson, Shradha Bhalla, Fei Wang, Miaojun Wang, Kai Zheng, Pravin K Narwankar, Lynne S Taylor

{"title":"Dissolution of copovidone-based amorphous solid dispersions: Influence of atomic layer coating, hydration kinetics, and formulation.","authors":"Emily G Benson, Dana E Moseson, Shradha Bhalla, Fei Wang, Miaojun Wang, Kai Zheng, Pravin K Narwankar, Lynne S Taylor","doi":"10.1016/j.xphs.2024.10.001","DOIUrl":"10.1016/j.xphs.2024.10.001","url":null,"abstract":"Atomic layer coating (ALC) is an emerging, solvent-free technique to coat amorphous solid dispersion (ASD) particles with a nanolayer ceramic coating that has been shown to improve powder characteristics and limit drug crystallization. Herein, we evaluate the impact of aluminum oxide coatings with varying thickness and conformality on the release behavior of ritonavir/copovidone ASDs. Release performance of powders, neat tablets, and formulated tablets was studied. Confocal fluorescence microscopy (CFM) was used to visualize particle hydration and phase separation during immersion of the ASD in aqueous media. CFM revealed particle hydration requires defects for solvent penetration, but coatings, regardless of thickness, had minor impacts on powder dissolution provided defects were present. In tablets where less surface area is exposed to the dissolution media due to gel formation, slowed hydration kinetics resulted in phase separation of the drug from the polymer in coated samples, limiting release. Formulation with two superdisintegrants, crospovidone and croscarmellose sodium, as well as lactose achieved ∼90% release in less than 10 minutes, matching the uncoated ASD particles of the same formulation. This study highlights the importance of hydration rate, as well as the utility of confocal fluorescence microscopy to provide insight into release and phase behavior of ASDs.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Particle formation in response to different protein formulations and containers: Insights from machine learning analysis of particle images. 针对不同蛋白质配方和容器的颗粒形成：从粒子图像的机器学习分析中获得启示。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-09 DOI: 10.1016/j.xphs.2024.09.017

Gabriella Milef, Saba Ghazvini, Indira Prajapati, Yu-Chieh Chen, Yibo Wang, Mehdi Boroumand

{"title":"Particle formation in response to different protein formulations and containers: Insights from machine learning analysis of particle images.","authors":"Gabriella Milef, Saba Ghazvini, Indira Prajapati, Yu-Chieh Chen, Yibo Wang, Mehdi Boroumand","doi":"10.1016/j.xphs.2024.09.017","DOIUrl":"10.1016/j.xphs.2024.09.017","url":null,"abstract":"Subvisible particle count is a biotherapeutics stability indicator widely used by pharmaceutical industries. A variety of stresses that biotherapeutics are exposed to during development can impact particle morphology. By classifying particle morphological differences, stresses that have been applied to monoclonal antibodies (mAbs) can be identified. This study aims to evaluate common biotherapeutic drug storage and shipment conditions that are known to impact protein aggregation. Two different studies were conducted to capture particle images using micro-flow imaging and to classify particles using a convolutional neural network. The first study evaluated particles produced in response to agitation, heat, and freeze-thaw stresses in one mAb formulated in five different formulations. The second study evaluated particles from two common drug containers, a high-density polyethylene bottle and a glass vial, in six mAbs exposed solely to agitation stress. An extension of this study was also conducted to evaluate the impact of sequential stress exposure compared to exposure to one stress alone, on particle morphology. Overall, the convolutional neural network was able to classify particles belonging to a particular formulation or container. These studies indicate that storage and shipping stresses can impact particle morphology according to formulation composition and mAb.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Using the refined Developability Classification System (rDCS) to guide the design of oral formulations. 使用改良的显影性分类系统 (rDCS) 指导口服制剂的设计。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-05 DOI: 10.1016/j.xphs.2024.09.022

Kristian Beran, Eline Hermans, René Holm, Kia Sepassi, Jennifer Dressman

{"title":"Using the refined Developability Classification System (rDCS) to guide the design of oral formulations.","authors":"Kristian Beran, Eline Hermans, René Holm, Kia Sepassi, Jennifer Dressman","doi":"10.1016/j.xphs.2024.09.022","DOIUrl":"10.1016/j.xphs.2024.09.022","url":null,"abstract":"The refined Developability Classification System (rDCS) provides a comprehensive animal-free approach for assessing biopharmaceutical risks associated with developing oral formulations. This work demonstrates practical application of a recently advanced rDCS framework guiding formulation design for six diverse active pharmaceutical ingredients (APIs) and compares rDCS classifications with those of the Biopharmaceutics Classification System (BCS). While the BCS assigns five of the APIs to class II/IV, indicating potentially unfavorable biopharmaceutical attributes, the rDCS provides a more nuanced risk assessment. Both BCS and rDCS assign acetaminophen to class I at therapeutic doses. Voriconazole and lemborexant (both BCS II) are classified in rDCS class I at therapeutic doses, indicating suitability for development as conventional oral formulations. Fedratinib is classified as BCS IV but the rDCS indicates a stratified risk (class I, IIa or IIb), depending on the relevance of supersaturation/precipitation in vivo. Voxelotor and istradefylline (both BCS II) belong to rDCS class IIb, requiring solubility enhancement to achieve adequate oral bioavailability. Comparing the rDCS analysis with literature on development and pharmacokinetics demonstrates that the rDCS reliably supports oral formulation design over a wide range of API characteristics, thus providing a strong foundation for guiding development.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Injectability of high concentrated suspensions using model microparticles. 使用模型微粒研究高浓度悬浮液的可注射性。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-05 DOI: 10.1016/j.xphs.2024.09.026

Kavin Kowsari, Lynn Lu, Steven C Persak, Guangli Hu, William Forrest, Robert Berger, Jeffrey C Givand, Sahab Babaee

{"title":"Injectability of high concentrated suspensions using model microparticles.","authors":"Kavin Kowsari, Lynn Lu, Steven C Persak, Guangli Hu, William Forrest, Robert Berger, Jeffrey C Givand, Sahab Babaee","doi":"10.1016/j.xphs.2024.09.026","DOIUrl":"10.1016/j.xphs.2024.09.026","url":null,"abstract":"Administration of high-concentrated suspension formulations (i.e., solid particles dispersed in a liquid vehicle) can be limited due to their greater propensity for needle occlusion. The physical interaction between the solid phase (i.e., particles), the vehicle (i.e., flow field), and injection devices could result in the formation of particle bridging or filtering, posing a major risk in dose delivery accuracy and injectability. Here, given the limited understanding on how clogging initiates in syringe and needle delivery systems, we report an experimental approach to fully characterize the transient injection behavior of suspensions. In particular, we first established a custom fluorescence tagging and imaging technique with integrated force sensor to enable visual observation of local particle concentrations and plunger force monitoring throughout injection. Then, we investigated the effects of key formulation properties and device parameters including particle concentration and morphology, carrier viscosity, injection rate, needle and syringe sizes, and tissue backpressure on the incidence of suspension particle jamming and needle clogging. We performed systematic benchmark studies demonstrating that increasing needle inner diameter (ID) and particle density considerably reduced clogging risk, while increasing vehicle viscosity, particle size, and tissue backpressure significantly increased clogging. The experimental framework presented is amenable to quantifying clogging risk in drug-loaded particle suspensions and provides a guideline to make informed decisions on the tradeoffs between creating particles for pharmaceutical impact and feasibility of injection delivery.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Investigating the effects of formulation variables on the disintegration of spray dried amorphous solid dispersion tablets. 研究配方变量对喷雾干燥无定形固体分散片崩解性的影响

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-05 DOI: 10.1016/j.xphs.2024.09.024

Wei Zhang, Prajwal Thool, Benjamin W Weitz, Hao Helen Hou

{"title":"Investigating the effects of formulation variables on the disintegration of spray dried amorphous solid dispersion tablets.","authors":"Wei Zhang, Prajwal Thool, Benjamin W Weitz, Hao Helen Hou","doi":"10.1016/j.xphs.2024.09.024","DOIUrl":"10.1016/j.xphs.2024.09.024","url":null,"abstract":"Amorphous solid dispersion (ASD) tablets based on hydrophilic polymer carriers may encounter disintegration challenges. In this work, the effect of different formulation composition variables on the ASD tablet disintegration performance was systematically studied. GDC-0334: copovidone (PVPVA) 60: 40 ASD prepared by spray drying was selected as the model ASD system. The effects of ASD loading, filler type and ratio, disintegrant type and level were then investigated using tablets made by direct compression process. Tablet disintegration time increased with the increase of ASD loading, especially when ASD loading exceeded 50 %. At the same tablet solid fraction, when lactose was used as the soluble filler, faster tablet disintegration was observed compared to the tablets with mannitol as the soluble filler. Among the three tested disintegrants, croscarmellose sodium performed the best in facilitating the ASD tablet disintegration, followed by sodium starch glycolate, and crospovidone was the poorest. When croscarmellose sodium was used as the disintegrant, 5 % level was sufficient to enable ASD tablet disintegration at 60 % ASD loading and further increase of croscarmellose sodium level to 8 % did not provide additional benefit. Water uptake experiments were performed on selected tablets and the results demonstrated a positive correlation with tablet disintegration time, indicating water penetration is a major contributing step for the disintegration of our ASD tablets. Overall, this work provides a rationale for excipient selection and insights into building a platform formulation approach for developing immediate-release ASD tablets.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synergistic effect of cyclodextrins and electrolytes at high concentrations on protein aggregation inhibition. 高浓度环糊精和电解质对蛋白质聚集抑制的协同效应

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-05 DOI: 10.1016/j.xphs.2024.10.004

Masakazu Fukuda, Kanako Takahashi, Toru Takarada, Shunsuke Saito, Masafumi Tanaka

{"title":"Synergistic effect of cyclodextrins and electrolytes at high concentrations on protein aggregation inhibition.","authors":"Masakazu Fukuda, Kanako Takahashi, Toru Takarada, Shunsuke Saito, Masafumi Tanaka","doi":"10.1016/j.xphs.2024.10.004","DOIUrl":"10.1016/j.xphs.2024.10.004","url":null,"abstract":"The stabilization of protein therapeutics against aggregation is crucial for maintaining their efficacy and safety. This study investigated the synergistic effects of cyclodextrins (CDs) and electrolytes at high concentrations on the stabilization of immunoglobulin G (IgG), insulin, and adeno-associated virus (AAV) vectors. The effects of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) combined with various electrolytes were evaluated using human plasma-derived IgG as a model protein. The HP-β-CD and L(+)-arginine hydrochloride combination synergistically increased the onset temperature of protein aggregation and inhibited the formation of soluble and insoluble aggregates during long-term storage. Notably, this synergistic effect was not observed when sucrose was used instead of HP-β-CD. Similar synergistic effects were observed with insulin and AAV vectors. The findings suggest that the stabilization mechanism could potentially involve enhanced interactions between HP-β-CD and IgG, preventing protein-protein interactions. However, the combination did not synergistically improve the solubility of free aromatic amino acids, including tyrosine and tryptophan. This study highlights the potential of using the combination of CDs and electrolytes as a promising formulation strategy for stabilizing complex protein therapeutics. Further studies are needed to elucidate the underlying mechanisms and generalize the approach to other proteins with varying physicochemical properties.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0