International Journal of Pharmaceutics最新文献

{"title":"Evaluation of aspartame as a co-former in the preparation of co-amorphous formulations of dipyridamole using spray drying","authors":"Md Kamruzzaman ,&nbsp;Helen Cathcart ,&nbsp;Peter McLoughlin ,&nbsp;Niall J. O’Reilly","doi":"10.1016/j.ijpharm.2024.124913","DOIUrl":"10.1016/j.ijpharm.2024.124913","url":null,"abstract":"<div><div>Co-amorphous systems (CAMs) have shown promise in addressing the challenges associated with poorly water-soluble drugs. However, the limited selection of co-formers and the use of lab-scale techniques for their preparation present challenges in fully utilizing the advantages of CAMs. In this study, we used aspartame (a methyl ester of the aspartic acid/phenylalanine) as a model dipeptide with the BCS class II drug dipyridamole, to prepare co-amorphous systems using spray drying. The feed solutions were prepared by dissolving the drug and co-former into methanol–water mixtures. The spray drying process was evaluated and solid-state properties were compared with those of the individual amino acids, amino acid mixtures and aspartame as co-formers. Co-amorphous systems prepared with aspartame (AspPhe) exhibited better solid-state properties, including a higher glass transition temperature (T_g), compared to the individual amino acids and the mixture of amino acids. Additionally, this formulation showed improved physical stability when stored at 25 °C/60 % RH conditions. Hirshfeld Surface (HS) analysis was employed to visualize and analyse the molecular interaction sites within the crystal structures of dipyridamole and aspartame. The observed interactions were then correlated with the molecular interactions identified through FT-IR spectroscopic analysis within the CAMs. The spectroscopic analysis revealed molecular interactions between the sites found at the shortest distances in the HS analysis. The dominant hydrogen bond interactions identified in the co-amorphous DPM-AspPhe system was found to contribute significantly to its improve stability. X-ray powder diffraction in non-ambient mode reveals that both temperature and humidity play a role in the crystallization of the co-amorphous DPM-AspPhe. Crystallization rates increased notably at high temperature and humidity. To predict stability under accelerated conditions, the crystallization rates from DPM-AspPhe were fitted to a modified Arrhenius equation. However, the predictive accuracy of the resulting model was limited to a specific range of conditions.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124913"},"PeriodicalIF":5.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Piperine solubility enhancement via DES formation: Elucidation of intermolecular interactions and impact of counterpart structure via computational and spectroscopic approaches","authors":"Sara A. Hassan ,&nbsp;Marwa A. Zaater ,&nbsp;Islam M. Abdel-Rahman ,&nbsp;Elsayed A. Ibrahim ,&nbsp;Ahmed M. El Kerdawy ,&nbsp;Sara A. Abouelmagd","doi":"10.1016/j.ijpharm.2024.124893","DOIUrl":"10.1016/j.ijpharm.2024.124893","url":null,"abstract":"<div><div>The development of new forms of existing APIs with enhanced physicochemical properties is critical for improving their therapeutic potential. In this context, ionic liquids (ILs) and deep eutectic solvents (DESs) have gained significant attention in recent years due to their unique properties and potential for solubility enhancement. In this study, we explore the role of different counterparts in the formation of IL/DESs with piperine (PI), a poorly water-soluble drug. After screening a library of fourteen counterpart molecules, ten liquid PI-counterpart systems were developed and investigated. Thermal analysis confirmed the formation of IL/DES, while computational and spectroscopic studies revealed that hydrogen bonding played a crucial role in the interaction between PI and the counterparts, confirming DES formation. The solubility enhancement of PI in these systems ranged from ∼ 36 % to 294 %, with PI-Oxalic acid (OA) exhibiting the highest saturation solubility (49.71 μg/mL) and PI-Ibuprofen (IB) the lowest (17.23 μg/mL). The presence of hydrogen bonding groups in counterparts was key to successful DES formation. A negative correlation was observed between solubility and logP (r =  − 0.75, p* = 0.0129), while a positive correlation was found between solubility and normalized polar surface area (PSA) (r = 0.68, p* = 0.029). PI-OA and PI-IB were located at the extreme ends of these regression lines, further validating the relationship between these properties and solubility enhancement. These findings highlight essential aspects of rational IL/DES design, optimizing their properties for broader applications.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124893"},"PeriodicalIF":5.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a novel hyaluronic acid/alginate/RANKL degradable microneedle patch for accelerating bone remodeling and orthodontic tooth movement through promoting osteoclastogenesis.","authors":"Yue Shan, Yu Jin, Xiaoqi Zhang, Yufei Tang, Wenli Lai, Jinfeng Liao, Mengjie Wu, Hu Long","doi":"10.1016/j.ijpharm.2024.124915","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2024.124915","url":null,"abstract":"<p><p>The prolonged duration of orthodontic treatment remains a significant concern for both orthodontists and patients. In this study, we developed a degradable microneedle (MN) patch composed of hyaluronic acid (HA) and sodium alginate (SA) for the delivery of receptor activator of nuclear factor-kappa B ligand (RANKL) to accelerate tooth movement. This MN patch which was crosslinked by calcium chloride (CaCl₂) exhibits adequate mechanical properties and favorable in vitro mucosal insertion ability. Moreover, the MN patch can achieve the sustained release of RANKL and maintain the biological stability of RANKL protein after one month of storage at -20 °C, 4 °C, or 37 °C. In vitro experiments using RAW264.7 cells indicated that the HA/SA/RANKL MN possessed excellent biocompatibility and could effectively induce osteoclast differentiation. In vivo application of the HA/SA/RANKL MN in rat models showed a remarkable effect in promoting osteoclast formation and accelerating tooth movement. These findings suggest that the degradable HA/SA/RANKL MN holds significant potential for enhancing tooth movement efficiency.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"124915"},"PeriodicalIF":5.3,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of gelatin nanoparticles’ size and charge on iontophoretic targeted deposition to the hair follicles","authors":"Jayanaraian F. Martins Andrade ,&nbsp;Agnes-Valencia Weiss ,&nbsp;Marcílio Cunha-Filho ,&nbsp;Guilherme M. Gelfuso ,&nbsp;Tais Gratieri ,&nbsp;Marc Schneider","doi":"10.1016/j.ijpharm.2024.124906","DOIUrl":"10.1016/j.ijpharm.2024.124906","url":null,"abstract":"<div><div>Hair follicles (HFs) represent a route of interest to drug delivery for treating several skin conditions. Iontophoresis, on the other hand, is a physical method to enhance drug permeation by applying a low electrical current to the formulation. HFs can be targeted following topical iontophoretic application, as they represent a pathway of lower electrical resistance, as well as a drug reservoir, in particular useful for nanoparticles (NPs), which can preferably accumulate in these structures. Combining both strategies may provide optimal results, but the literature still lacks evidence of the ideal NP characteristics for the iontophoretic drug delivery targeting the HFs. Here, we aimed to evaluate the effect of gelatin NPs’ size and charge under iontophoresis application on NPs’ deposition into the HFs. Four gelatin NP formulations were produced with varying gelatin concentrations and gelatin types (positively charged type A and negatively charged type B), with sizes ranging from 220 to 770 nm. A fluorescent dye, TRITC-dextran 150 kDa, was encapsulated for monitoring NPs deposition. Cutaneous penetration experiments were performed <em>in vitro</em> with and without iontophoresis for 6 h with pig ear skin. The deposition profile was assessed by confocal laser scanning microscopy. Photomicrographs showed a higher accumulation of the larger positively charged NPs (AL), reaching deeper portions of HFs, and showed iontophoresis further increased their deposition, resulting in the highest signal. In conclusion, these findings shed light on the applications of NPs and bring novel treatment opportunities for several diseases compromising the hair follicles.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124906"},"PeriodicalIF":5.3,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Citicoline eluting hydrogels for therapeutic contact lenses intended to treat neurodegenerative diabetic ocular diseases","authors":"João Teixeira ,&nbsp;Zélia Lumack do Monte ,&nbsp;Sandra Tenreiro ,&nbsp;Madalena Salema-Oom ,&nbsp;Diana C. Silva ,&nbsp;Benilde Saramago ,&nbsp;Ana Paula Serro","doi":"10.1016/j.ijpharm.2024.124908","DOIUrl":"10.1016/j.ijpharm.2024.124908","url":null,"abstract":"<div><div>Ophthalmic neurodegenerative diseases related to diabetes, such as glaucoma and retinopathy, are among the major causes of blindness in the world. Citicoline (CIT) in the form of eye drops is currently used for the treatment/prevention of these diseases, which affect the posterior segment of the eye. To ensure the drug penetration into the back of the eye, frequent instillations of highly concentrated drug solutions are required with potential side effects. Drug-loaded soft contact lenses (SCLs) may be an effective alternative to the conventional eye drop treatment, since they may enable a sustained drug release during daily wear, ensuring a higher drug bioavailability, and avoiding drug waste. In this work, one 2-hydroxyethyl methacrylate (HEMA) based hydrogel was functionalised with <em>N</em>-(3-aminopropyl) methacrylamide hydrochloride (APMA), molecularly imprinted with CIT and loaded with the same drug. The material was extensively characterised, in terms of morphology, optical, mechanical, and physical–chemical properties, namely, equilibrium water content, wettability, oxygen and ionic permeability, Young’s modulus, shear deformation, transmittance and refractive index, before and after steam sterilisation. Additionally, the tendency of the material to adsorb proteins of the lachrymal fluid was evaluated and its biocompatibility was assessed by irritation and cytotoxicity assays. Comparison with the non-functionalised and non-imprinted hydrogel showed that the modified hydrogel led to a sustained <em>in vitro</em> release of a much higher amount of CIT than the original one, while keeping typical values for physical–chemical properties of SCLs. The drug-loaded material resisted steam sterilisation and proved to be biocompatible, demonstrating adequate properties to be used in therapeutic SCLs for the prophylaxis/treatment of neurodegenerative diabetic ocular diseases. The neuroprotective effect of the released drug was confirmed with tests using porcine retinal explants.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124908"},"PeriodicalIF":5.3,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of lubricants type and particle size on the rheological properties and aerosolization behavior of dry powder inhalers","authors":"Jiayi Li ,&nbsp;Xianhong He ,&nbsp;Ying Sun ,&nbsp;Ruxiao Song ,&nbsp;Xuhong Ren ,&nbsp;Xin Zhang ,&nbsp;Jian Guan ,&nbsp;Shirui Mao","doi":"10.1016/j.ijpharm.2024.124911","DOIUrl":"10.1016/j.ijpharm.2024.124911","url":null,"abstract":"<div><div>A commonly used strategy to improve aerosolization behavior of carrier-based dry powder inhalers (DPIs) is the addition of magnesium stearate as a lubricant, yet it may also negatively affect properties of DPIs. Thus, the aim of this study was to find lubricants that could be used as alternatives of magnesium stearate and meanwhile verify the applicability of using powder rheological properties to predict the performance of different lubricants in DPIs. Here, using fluticasone propionate as a model drug, LH200 as the carrier, influence of lubricants type and particle size, including magnesium stearate, sodium stearate, Leucine, sodium stearate fumarate, Compritol® 888 ATO, and Compritol® HD5 ATO, on the physicochemical properties, powder rheology and aerosolization behavior of the DPI formulations was characterized. Further, the relationship between powder rheological parameters and <em>in-vitro</em> drug deposition parameter, fine particle fraction (FPF), were explored, and the contribution of powder flowability and adhesion was evaluated using principal component analysis (PCA). The results showed that magnesium stearate, sodium stearate and smaller sized leucine significantly reduced the basic flowability energy, aeration energy and Permeability of the DPI formulations, leading to improved aerosolization behavior. A robust linear correlation was established between rheological parameters and FPF. PCA showed that in lubricants containing formulations, the contribution of flowability (74.69%) was greater than that of adhesion (25.31%). In conclusion, sodium stearate and smaller particle size Leucine can be considered as substitutes of magnesium stearate in DPI formulations.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124911"},"PeriodicalIF":5.3,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA-templated nanosheets for enhanced chemodynamic therapy and gene therapy to inhibit tumor recurrence and metastasis","authors":"Danna Sun ,&nbsp;Yuwei Song ,&nbsp;Wenyan Gao ,&nbsp;Boyang Lin ,&nbsp;Bei Wang ,&nbsp;Xinjian Yang ,&nbsp;Shaochun Li ,&nbsp;Yi Jin ,&nbsp;Jinchao Zhang","doi":"10.1016/j.ijpharm.2024.124910","DOIUrl":"10.1016/j.ijpharm.2024.124910","url":null,"abstract":"<div><div>Recurrence and metastasis stand as the primary contributors to mortality among patients with triple-negative breast cancer post-surgery, presenting a formidable clinical obstacle. Chemodynamic therapy (CDT), leveraging metal-ion-mediated Fenton-like reactions within the tumor microenvironment (TME), emerges as a promising avenue for addressing cancer metastasis. Despite recent progress, challenges such as tumor cell antioxidant defenses and epithelial-mesenchymal transition (EMT) impede the efficacy of CDT. Here, we introduce a novel approach using DNA-templated nanosheets (Dz-MnO₂) that combine the functions of Mn²⁺-mediated CDT and DNAzyme-mediated gene therapy to suppress tumor growth and metastasis. The Dz-MnO₂ nanosheets respond effectively to the TME, releasing Mn²⁺ and DNAzyme. The DNAzyme exhibits mRNA cleavage activity, specifically targeting oncogenic transcripts to reduce tumor progression. Mn²⁺ not only facilitates a Fenton-like reaction, enhancing the chemodynamic treatment effect, but also serves as a cofactor for DNAzyme, improving its catalytic efficiency. Concurrently, the nanosheets robustly silence the Twist1 gene, mitigating the EMT process and reinforcing CDT efficacy by suppressing apoptosis resistance. Results indicate that Dz-MnO₂ nanosheets efficiently polarize M2-tumor-associated macrophages (TAMs) into M1-TAMs by locally mitigating tumor hypoxia <em>via</em> catalyzing the decomposition of H₂O₂ into O₂. This collaborative strategy presents a promising approach to enhance CDT, effectively inhibiting tumor recurrence and metastasis.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124910"},"PeriodicalIF":5.3,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DES/O microemulsion for solubilizing and delivering curcumin via the nasal administration to treat acute asthma","authors":"Yiwen Liu ,&nbsp;Ruirui Liu ,&nbsp;Qingliang Yang ,&nbsp;Gensheng Yang","doi":"10.1016/j.ijpharm.2024.124900","DOIUrl":"10.1016/j.ijpharm.2024.124900","url":null,"abstract":"<div><div>As a natural small molecule drug derived from turmeric, curcumin is known for its good biosafety and a range of beneficial effects, including anti-inflammatory, anti-spasmodic, antioxidant, antibacterial, anti-tumor, and neuroprotective effects. Even though, its insolubility in water and instability severely limit its bioavailability and clinical applications. The present study developed a deep eutectic solvent (DES) in oil microemulsion (DES/O-ME) system loaded with Cur for intranasal administration, aiming to enhance both the solubility and permeability of Cur to significantly increase its bioavailability. The project first constructed and screened the optimal choline chloride-based DES. Subsequently, the DES/O-ME system was prepared and optimized to achieve uniform particle size and stability using a pseudo-ternary phase diagram and electrical conductivity measurements. The resulting DES/O-ME system was thoroughly evaluated for its solubilization efficacy, permeability, mucosal cytotoxicity, and stability. Additionally, the therapeutic efficacy of the Cur-DES/O-ME was assessed in vivo using a murine model of allergic asthma. This comprehensive evaluation highlights the potential of the DES/O-ME system as a promising intranasal drug delivery platform to overcome the limitations of curcumin’s bioavailability and clinical application.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124900"},"PeriodicalIF":5.3,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FRESH 3D printing of zoledronic acid-loaded chitosan/alginate/hydroxyapatite composite thermosensitive hydrogel for promoting bone regeneration","authors":"Reem Khaled Wassif ,&nbsp;Baher A. Daihom ,&nbsp;Mohammed Maniruzzaman","doi":"10.1016/j.ijpharm.2024.124898","DOIUrl":"10.1016/j.ijpharm.2024.124898","url":null,"abstract":"<div><div>The aim of this study was to develop a composite thermosensitive hydrogel for bone regeneration applications. This hydrogel consisted of chitosan, alginate and hydroxyapatite, and was loaded with zoledronic acid as a model drug. The feasibility of three-dimensional (3D) printing of the thermosensitive hydrogel using the extrusion based technique was investigated. The 3D printing technique called Freeform Reversible Embedded Suspended Hydrogel (FRESH) printing was employed for this purpose. To characterize the composite hydrogels, several tests were conducted. The gelation time, rheological properties, and <em>in vitro</em> drug release were analyzed. Additionally, the cell viability test on human osteosarcoma MG-63 cells for the composite hydrogel was assessed using an MTT assay. The results of the study showed that the zoledronic acid-loaded composite thermosensitive hydrogel was successfully printed using the FRESH 3D printing technique which was not possible otherwise i.e., by using traditional 3D printing techniques. Further examination of the printed constructs using a Scanning Electron Microscope revealed the presence of porous and layered structures. The gelation times of the composite thermosensitive hydrogel was determined to be 10 and 20 min, respectively for scaffolds with and without HA, indicating the successful formation of the gel within a reasonable time to the FRESH technique. The flow behavior of the hydrogel was found to be pseudoplastic, following a non-Newtonian flow pattern with Farrow’s constant (N) values of 1.708 and 1.853 for scaffolds with and without hydroxyapatite, respectively. In terms of drug release, scaffolds prepared with and without hydroxyapatite reached nearly 100% of zoledronic acid release in 360 h and 48 h, respectively. The cell viability test on human osteosarcoma MG-63 cells using MTT assay has shown increased cell viability % in the case of composite hydrogel, indicating biocompatibility of the scaffold. Overall, this study successfully developed a composite thermosensitive hydrogel loaded with zoledronic acid for bone regeneration applications and was 3D printed using the FRESH 3D printing technique. The results of this study provide valuable insights into the potential use of this composite hydrogel for future biomedical applications.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124898"},"PeriodicalIF":5.3,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NMR coupled with multivariate data analysis for monitoring the degradation of a formulated therapeutic monoclonal antibody","authors":"Cédric Schaefer ,&nbsp;Emmanuel Cornet ,&nbsp;Martial Piotto","doi":"10.1016/j.ijpharm.2024.124894","DOIUrl":"10.1016/j.ijpharm.2024.124894","url":null,"abstract":"<div><div>The function of a protein is directly coupled to its higher-order structure (HOS). Deviations in this critical quality attribute (CQA) may be linked to a decrease in the efficacy and/or safety of the final therapeutic product. High-resolution nuclear magnetic resonance (NMR) spectroscopy has been recently highlighted for protein HOS characterization, thanks to its ability to capture small changes at the molecular and structural levels (primary, secondary, tertiary and quaternary structures). The present study was carried out to demonstrate the ability of NMR (1D ¹H and 2D ¹H-¹³C experiments) coupled with multivariate data analysis (PCA and PLS regression) to monitor the degradation of a formulated mAb-like protein and for the simultaneous quantification of related CQAs, i.e., potency, purity and impurities (aggregates and fragments). The results indicate that this approach could be applied to mitigate product quality risks during development, manufacturing and stability studies of mAb therapeutics.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124894"},"PeriodicalIF":5.3,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}