International Journal of Pharmaceutics最新文献_第5页

Development and comparative analysis of clobetasol-loaded microneedle patches versus clobetasol propionate ointment in experimental induced-psoriasis model

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2025-03-10 DOI: 10.1016/j.ijpharm.2025.125423

Zohreh Bazargani , Mohammad Khorram , Kamiar Zomorodian , Mehdi Ghahartars , Navid Omidifar

The utilization of dissolvable microneedles (MNs) is a promising and cutting-edge approach to drug delivery for the treatment of psoriasis, an autoimmune skin disorder characterized by the appearance of red, scaly patches on the skin. This study presents the development of a dissolving MN patch made of polyvinylpyrrolidone for the purpose of delivering Clobetasol 17-Propionate through the skin. The MN patches were evaluated for their physical characteristics, including morphology, solubility, strength, and ability to penetrate the skin. This evaluation was conducted on both unloaded and drug-loaded MN patches to determine their suitability for future applications. The manufacturing of 484 pyramidal-shaped tips, each measuring roughly 400 µm in height, was demonstrated by microscopy photographs. Compression tests revealed that the MN patch could endure a force greater than 1 N/needle while displacing around 300 µm, confirming the needle’s ability to penetrate the stratum corneum. Following H&E staining, the penetration depth in mice skin was determined to be around 200 µm. The MN tips exhibited rapid drug release within a 10-minute timeframe, while the MN patch dissolved in the mice skin in roughly 20 min. An animal model was utilized to examine the effects of the produced patches on the treatment of psoriasis. Psoriasis was artificially induced in three groups of mice using imiquimod cream, applied for eight consecutive days to evaluate the inhibitory effect of clobetasol on exacerbating the disease. This assessment was accomplished using two methods: applying clobetasol ointment and using CP-loaded MNs. This innovative drug delivery system demonstrated encouraging results in terms of quick and effective administration, highlighting the potential of dissolvable MNs for psoriasis treatment.

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引用次数: 0

Scale-up of a low-temperature spray-drying process for a tuberculosis vaccine candidate using lab-scale equipment

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2025-03-10 DOI: 10.1016/j.ijpharm.2025.125456

Maximilian Aisenstat , Joseph McCollum , Mani Ordoubadi , Hui Wang , Zahra Minootan , Alana Gerhardt , Andrew R. Martin , Christopher B. Fox , Reinhard Vehring

Laboratory-scale spray drying can be a useful tool in developing new dry powder formulations for the delivery of biologics such as therapeutic proteins or vaccines. Low-temperature drying is often used in these processes to prevent the exposure of biologics to harsh conditions that could potentially lead to degradation or instability of the final product. However, low-temperature drying on small-scale equipment can result in very low production rates that may not be practical for generating sufficient material for studies requiring larger sample quantities, such as key preclinical or toxicology studies. This study demonstrates a scale-up effort for a spray dried adjuvanted protein tuberculosis (TB) vaccine candidate using a custom lab-scale spray dryer. To achieve higher throughput without compromising the stability of the powder and biologic material, a process model for the spray dryer was used to determine optimal processing parameters and establish general vaccine powder manufacturing guidelines, such as minimizing exposure to high temperatures and relative humidity during drying. Maximizing dryer throughput and increasing overall feed concentration resulted in a tenfold increase in production rate using lab-scale equipment, such that 97.6 g of powder (the equivalent of about 5,000 human doses) could be produced using a lab-scale spray dryer in a single 6-hour spray drying run.

{"title":"Scale-up of a low-temperature spray-drying process for a tuberculosis vaccine candidate using lab-scale equipment","authors":"Maximilian Aisenstat , Joseph McCollum , Mani Ordoubadi , Hui Wang , Zahra Minootan , Alana Gerhardt , Andrew R. Martin , Christopher B. Fox , Reinhard Vehring","doi":"10.1016/j.ijpharm.2025.125456","DOIUrl":"10.1016/j.ijpharm.2025.125456","url":null,"abstract":"<div><div>Laboratory-scale spray drying can be a useful tool in developing new dry powder formulations for the delivery of biologics such as therapeutic proteins or vaccines. Low-temperature drying is often used in these processes to prevent the exposure of biologics to harsh conditions that could potentially lead to degradation or instability of the final product. However, low-temperature drying on small-scale equipment can result in very low production rates that may not be practical for generating sufficient material for studies requiring larger sample quantities, such as key preclinical or toxicology studies. This study demonstrates a scale-up effort for a spray dried adjuvanted protein tuberculosis (TB) vaccine candidate using a custom lab-scale spray dryer. To achieve higher throughput without compromising the stability of the powder and biologic material, a process model for the spray dryer was used to determine optimal processing parameters and establish general vaccine powder manufacturing guidelines, such as minimizing exposure to high temperatures and relative humidity during drying. Maximizing dryer throughput and increasing overall feed concentration resulted in a tenfold increase in production rate using lab-scale equipment, such that 97.6 g of powder (the equivalent of about 5,000 human doses) could be produced using a lab-scale spray dryer in a single 6-hour spray drying run.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"674 ","pages":"Article 125456"},"PeriodicalIF":5.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615470","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}

引用次数: 0

Chitosan/hydroxypropylmethylcellulose based-mucoadhesive gastroretentive microparticles containing curcumin intended for the prevention of gastric ulcers 基于壳聚糖/羟丙基甲基纤维素的含有姜黄素的黏附性胃黏膜微颗粒，用于预防胃溃疡

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2025-03-09 DOI: 10.1016/j.ijpharm.2025.125454

Maurício Palmeira Chaves de Souza , Suzana Gonçalves Carvalho , Larissa Spósito, Bruna Almeida Furquim de Camargo, Tais Maria Bauab, Andréia Bagliotti Meneguin, Marlus Chorilli

Gastric ulcer (GU) is a disease characterized by ulcerative lesions on the surface of the stomach mucosa caused mainly by health-related conditions, non-steroidal anti-inflammatory drugs (NSAIDs) use, and Helicobacter pylori infections. The treatment for this disease requires that the drug remains in contact with the site of action, however, the residence time of conventional dosage forms in this organ is limited due to gastric emptying. Curcumin (CUR) is a compound obtained from the rhizomes of the Curcuma longa plant and has been used in traditional Indian medicine for many centuries. However, its use is limited because it has low solubility in aqueous media. In addition, the treatment of gastric diseases requires the drug to remain in contact with the area, but the residence time of conventional dosage forms in this organ is limited. One strategy to overcome these limitations is the use of a gastroretentive and mucoadhesive delivery system. Therefore, this study aimed to develop polymeric chitosan and hydroxypropylmethylcellulose-based microparticles for the release of CUR and to evaluate their in vivo gastroprotective action. The microparticles had a spherical shape and size between 620 and 820 µm, and the encapsulation efficiency was over 50 %, with complete release of CUR after 24 h. Thermal analysis showed changes in the structure of the polymers and CUR, suggesting the establishment of new supramolecular interactions. Microparticles showed high bioadhesive forces to the mucin disc. This set of results, suggest that these systems are promising tools for the prevention of gastric lesions associated with the use of NSAIDs, with a gastroprotective index similar to that conferred by omeprazole.

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引用次数: 0

Deciphering a crosstalk between biological cues and multifunctional nanocarriers in lung cancer therapy

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2025-03-08 DOI: 10.1016/j.ijpharm.2025.125395

Sharon George , Hendry Saju , Tharun Jaikumar , Reshma Raj , R. Nisarga , Samruddhi Sontakke , Jaiprakash Sangshetti , Manash K. Paul , Rohidas B. Arote

In recent years, the utilization of nanocarriers has significantly broadened across a diverse spectrum of biomedical applications. However, the clinical translation of these tiny carriers is limited and encounters hurdles, particularly in the intricate landscape of the tumor microenvironment. Lung cancer poses unique hurdles for nanocarrier design. Multiple physiological barriers hinder the efficient drug delivery to the lungs, such as the complex anatomy of the lung, the presence of mucus, immune responses, and rapid clearance mechanisms. Overcoming these obstacles necessitates a targeted approach that minimizes off-target effects while effectively penetrating nanoparticles/cargo into specific lung tissues or cells. Furthermore, understanding the cellular uptake mechanisms of these nano carriers is also essential. This knowledge aids in developing nanocarriers that efficiently enter cells and transfer their payload for the most effective therapeutic outcome. Hence, a thorough understanding of biological cues becomes crucial in designing multifunctional nanocarriers tailored for treating lung cancer. This review explores the essential biological cues critical for developing a flexible nanocarrier specifically intended to treat lung cancer. Additionally, it discusses advancements in nanotheranostics in lung cancer.

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引用次数: 0

Formulation and evaluation of oxygen microbubbles stabilised in a hydrogel to potentiate radiotherapy

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2025-03-08 DOI: 10.1016/j.ijpharm.2025.125443

Ashok David Jose , Celine Hui-Ning Chong , Ernest Cheah , Jagdish Jaiswal , Zimei Wu , Sachin Sunil Thakur

Background

Tumour hypoxia poses a significant challenge in cancer treatment. There is mounting evidence that reoxygenating tumours increases their sensitivity to conventional cancer therapies. Oxygenated microbubbles (OMB) show promise for this application but suffer from poor stability and rapid clearance. Embedding OMB in a thermosensitive hydrogel (OMBHG) may prolong tumour oxygenation and improve therapeutic outcomes.

Objectives

To formulate and evaluate OMB loaded in a temperature sensitive hydrogel on an in vitro model of tumour hypoxia.

Methods

OMB generated from a liposomal precursor were dispersed at various concentrations in a poloxamer hydrogel. OMB size, hydrogel rheology, injectability, oxygen loading/release, and impact on efficacy of radiotherapy against HCT116 colon cancer cells under hypoxia/normoxia were evaluated.

Results

DSPC:DSPE-PEG2000 (94:6 molar ratio) liposomes dispersed in a poloxamer 407: poloxamer 188 (21:6.5 % w/w) hydrogel generated OMB predominantly sized < 1 µm. OMBHG formulations were deemed injectable (force to inject < 38 N) at 20 °C and gelled before 37 °C and demonstrated both greater oxygen loading and prolonged oxygen release than OMB alone. Cancer cells were significantly less sensitive to radiotherapy under hypoxic conditions. Pre-treatment of the cells with OMB or OMBHG enhanced radiotherapy significantly, reducing clonogenic survival rates in HCT116 cells by 78 % in hypoxic conditions and by 68 % in normoxic conditions (p < 0.0001 in both cases). Notably, this treatment restored the radiotherapy sensitivity of hypoxic cells to the levels seen with normoxic cells.

Conclusion

Reoxygenation with a newly developed OMB hydrogel formulation effectively sensitised HCT116 to radiotherapy in vitro. Ongoing studies are exploring the importance of reoxygenation rate and extent for optimal tumour sensitisation.

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引用次数: 0

Best practice for the size analysis of nanomedicines – An iron sucrose case study

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2025-03-08 DOI: 10.1016/j.ijpharm.2025.125452

Ryan T. Coones , Ines Nikolic , Remo Eugster , Dora Mehn , Vivan Tong , Paola Luciani , Caterina Minelli

Iron sucrose is used in the parenteral treatment of iron deficiency anaemia. A number of iron sucrose similars have been developed alongside the original product. These products consist of colloidal iron with particles in the nanometre range stabilised by sucrose molecules. Dynamic light scattering (DLS) is the method of choice for the qualification of iron sucrose products in terms of particle size. However, the broad range of instrumentation and accessories available today for the execution of these measurements requires that best laboratory practice is established to ensure measurement comparability and consistent product quality. In this work, we have examined the measurement of iron sucrose particle size by DLS using a range of instrument models and manufacturers and compared results. We performed transmission electron microscopy with cryogenic capability to support DLS data interpretation. We find that DLS results are consistent when equivalent settings are selected across instruments, we discuss the experimental parameters of importance for high-quality measurements and present preliminary data for emerging modalities. Although focussed on iron sucrose products, the outcome of this work is relevant to the analysis of other types of nanoparticle-based products.

{"title":"Best practice for the size analysis of nanomedicines – An iron sucrose case study","authors":"Ryan T. Coones , Ines Nikolic , Remo Eugster , Dora Mehn , Vivan Tong , Paola Luciani , Caterina Minelli","doi":"10.1016/j.ijpharm.2025.125452","DOIUrl":"10.1016/j.ijpharm.2025.125452","url":null,"abstract":"<div><div>Iron sucrose is used in the parenteral treatment of iron deficiency anaemia. A number of iron sucrose similars have been developed alongside the original product. These products consist of colloidal iron with particles in the nanometre range stabilised by sucrose molecules. Dynamic light scattering (DLS) is the method of choice for the qualification of iron sucrose products in terms of particle size. However, the broad range of instrumentation and accessories available today for the execution of these measurements requires that best laboratory practice is established to ensure measurement comparability and consistent product quality. In this work, we have examined the measurement of iron sucrose particle size by DLS using a range of instrument models and manufacturers and compared results. We performed transmission electron microscopy with cryogenic capability to support DLS data interpretation. We find that DLS results are consistent when equivalent settings are selected across instruments, we discuss the experimental parameters of importance for high-quality measurements and present preliminary data for emerging modalities. Although focussed on iron sucrose products, the outcome of this work is relevant to the analysis of other types of nanoparticle-based products.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"674 ","pages":"Article 125452"},"PeriodicalIF":5.3,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596897","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}

引用次数: 0

Regulation of nanoparticle exocytosis direction via receptors transfer: A novel strategy to enhance therapeutic efficacy of semaglutide

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2025-03-08 DOI: 10.1016/j.ijpharm.2025.125439

Yating Wang, Mingjie Ni, Minyi Huang, Liyun Xing, Xi Liu, Fuya Jia, Yuan Huang

Coumaric acid (CA) is a typical nutrient required in relatively high quantities by the body. It has been proved CA could specifically bind to monocarboxylate Transporter-1 (MCT-1) receptors, a transporter protein expressed on the surface of intestinal epithelial cells, to facilitate its cellular uptake. Although our preliminary research demonstrated semaglutide (SEM) loaded CA modified nanoparticles (SEM@CNP) could improve the absorption of SEM to some extent, the oral bioavailability still remained suboptimal owing to the lysosomal degradation. To address this issue, INF-7 (peptide chain GLFEAIEGFIENGWEGMIDGWYG) and chloroquine (CQ), two lysosomal escape agents (LEAs) with different mechanisms of action, were incorporated with SEM@CNP for oral delivery (SEM@CNP + INF-7, SEM@CNP + CQ). In type II diabetes mice models, SEM@CNP + CQ effectively inhibited postprandial glucose rise with a relative pharmacological bioavailability of 20.63 ± 2.99 %, 1.73 times higher than SEM@CNP (11.90 ± 4.56 %). Mechanistic studies revealed that: 1) after adding LEAs, the exocytosis preference of nanoparticles was altered, tending towards basolateral exocytosis apparently. Regulated exocytosis directionality was linked to the spatial redistribution of MCT-1 receptors. 2) among the two LEAs, CQ demonstrated superior efficacy compared to INF-7. This superiority was attributed to the earlier onset of action and more pronounced degree of membrane disruption induced by CQ. This research provided new insights for the design of oral delivery systems for peptidic drugs.

{"title":"Regulation of nanoparticle exocytosis direction via receptors transfer: A novel strategy to enhance therapeutic efficacy of semaglutide","authors":"Yating Wang, Mingjie Ni, Minyi Huang, Liyun Xing, Xi Liu, Fuya Jia, Yuan Huang","doi":"10.1016/j.ijpharm.2025.125439","DOIUrl":"10.1016/j.ijpharm.2025.125439","url":null,"abstract":"<div><div>Coumaric acid (CA) is a typical nutrient required in relatively high quantities by the body. It has been proved CA could specifically bind to monocarboxylate Transporter-1 (MCT-1) receptors, a transporter protein expressed on the surface of intestinal epithelial cells, to facilitate its cellular uptake. Although our preliminary research demonstrated semaglutide (SEM) loaded CA modified nanoparticles (SEM@CNP) could improve the absorption of SEM to some extent, the oral bioavailability still remained suboptimal owing to the lysosomal degradation. To address this issue, INF-7 (peptide chain GLFEAIEGFIENGWEGMIDGWYG) and chloroquine (CQ), two lysosomal escape agents (LEAs) with different mechanisms of action, were incorporated with SEM@CNP for oral delivery (SEM@CNP + INF-7, SEM@CNP + CQ). In type II diabetes mice models, SEM@CNP + CQ effectively inhibited postprandial glucose rise with a relative pharmacological bioavailability of 20.63 ± 2.99 %, 1.73 times higher than SEM@CNP (11.90 ± 4.56 %). Mechanistic studies revealed that: 1) after adding LEAs, the exocytosis preference of nanoparticles was altered, tending towards basolateral exocytosis apparently. Regulated exocytosis directionality was linked to the spatial redistribution of MCT-1 receptors. 2) among the two LEAs, CQ demonstrated superior efficacy compared to INF-7. This superiority was attributed to the earlier onset of action and more pronounced degree of membrane disruption induced by CQ. This research provided new insights for the design of oral delivery systems for peptidic drugs.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"674 ","pages":"Article 125439"},"PeriodicalIF":5.3,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596851","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}

引用次数: 0

A multipurpose silicone elastomer vaginal ring releasing dapivirine and Cu2+/Zn2+ ions for HIV prevention and non-hormonal contraception

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2025-03-08 DOI: 10.1016/j.ijpharm.2025.125442

Xin Shen, Peter Boyd, Yahya H. Dallal Bashi , Clare F. McCoy, Xinyu Zhao, R. Karl Malcolm

A dapivirine (DPV)-releasing vaginal ring (DapiRing®, containing 25 mg DPV) has been approved in various African countries for prevention of human immunodeficiency virus type 1 (HIV-1). Current research is focused on next-generation multipurpose prevention technology (MPT) vaginal rings that additionally provide contraception, and a combination dapivirine + levonorgestrel ring is in clinical development. However, hormonal contraceptives have numerous side effects and contraindications, and many women are interested in hormone-free contraceptive options. Copper and zinc have well documented spermicidal activity; for example, copper intrauterine devices—comprising a copper metal wire fitted to a polyethylene frame and releasing cupric (Cu²⁺) ions—have a long history of use as a long-acting reversible non-hormonal form of contraception. Here, we report a multipurpose vaginal ring offering sustained release of DPV, Cu²⁺ ions, and Zn²⁺ ions. Matrix-type silicone elastomer vaginal rings containing different combinations of DPV (25 mg) and various copper/zinc substances (copper nanopowders, zinc nanopowders, copper sulphate pentahydrate, and zinc acetate dihydrate) were successfully manufactured by injection molding. DPV and the metal nanopowders were stable during manufacturing; partial dehydration occurred with copper sulphate pentahydrate and zinc acetate dihydrate. Incorporation of copper/zinc substances had minimal impact on DPV release, and the formulations produced similar DPV release compared with DapiRing®. Rings containing metal salts released significantly more Cu²⁺/Zn²⁺ ions than those containing metal nanopowders, and greater quantities of Cu²⁺/Zn²⁺ ions compared with marketed copper IUDs or experimental copper-zinc IUDs. The results demonstrate that copper/zinc metals and salts can be effectively incorporated into and released from silicone elastomer vaginal rings and are compatible with DPV. The inclusion of copper/zinc offers potential as non-hormonal contraception and warrants further investigation in the context of MPTs.

{"title":"A multipurpose silicone elastomer vaginal ring releasing dapivirine and Cu2+/Zn2+ ions for HIV prevention and non-hormonal contraception","authors":"Xin Shen, Peter Boyd, Yahya H. Dallal Bashi , Clare F. McCoy, Xinyu Zhao, R. Karl Malcolm","doi":"10.1016/j.ijpharm.2025.125442","DOIUrl":"10.1016/j.ijpharm.2025.125442","url":null,"abstract":"<div><div>A dapivirine (DPV)-releasing vaginal ring (DapiRing®, containing 25 mg DPV) has been approved in various African countries for prevention of human immunodeficiency virus type 1 (HIV-1). Current research is focused on next-generation multipurpose prevention technology (MPT) vaginal rings that additionally provide contraception, and a combination dapivirine + levonorgestrel ring is in clinical development. However, hormonal contraceptives have numerous side effects and contraindications, and many women are interested in hormone-free contraceptive options. Copper and zinc have well documented spermicidal activity; for example, copper intrauterine devices—comprising a copper metal wire fitted to a polyethylene frame and releasing cupric (Cu<sup>2+</sup>) ions—have a long history of use as a long-actingreversible non-hormonal form of contraception. Here, we report a multipurpose vaginal ring offering sustained release of DPV, Cu<sup>2+</sup> ions, and Zn<sup>2+</sup> ions. Matrix-type silicone elastomer vaginal rings containing different combinations of DPV (25 mg) and various copper/zinc substances (copper nanopowders, zinc nanopowders, copper sulphate pentahydrate, and zinc acetate dihydrate) were successfully manufactured by injection molding. DPV and the metal nanopowders were stable during manufacturing; partial dehydration occurred with copper sulphate pentahydrate and zinc acetate dihydrate. Incorporation of copper/zinc substances had minimal impact on DPV release, and the formulations produced similar DPV release compared with DapiRing®. Rings containing metal salts released significantly more Cu<sup>2+</sup>/Zn<sup>2+</sup> ions than those containing metal nanopowders, and greater quantities of Cu<sup>2+</sup>/Zn<sup>2+</sup> ions compared with marketed copper IUDs or experimental copper-zinc IUDs. The results demonstrate that copper/zinc metals and salts can be effectively incorporated into and released from silicone elastomer vaginal rings and are compatible with DPV. The inclusion of copper/zinc offers potential as non-hormonal contraception and warrants further investigation in the context of MPTs.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"674 ","pages":"Article 125442"},"PeriodicalIF":5.3,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596891","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}

引用次数: 0

Additive effects of the new viscosity-reducing and stabilizing excipients for monoclonal antibody formulation

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2025-03-08 DOI: 10.1016/j.ijpharm.2025.125451

Monika Prašnikar , Maja Bjelošević Žiberna , Nika Kržišnik , Robert Roškar , Iztok Grabnar , Aleš Žula , Pegi Ahlin Grabnar

The subcutaneous administration of biopharmaceuticals is advantageous over intravenous administration, particularly with regard to improved patient compliance. However, in highly concentrated protein formulations lower viscosity of the formulation and stability of the protein is difficult to achieve. One approach involves using the viscosity-reducing excipients to diminish the interactions between protein molecules. In this context, the main objective of the study was to develop an optimal formulation for a model monoclonal antibody (mAb) and to evaluate new test compounds as viscosity-reducing agents. The test compounds were investigated both individually at increasing concentrations up to 200 mM and in combinations for their viscosity-reducing effect. Our results showed that all individual test compounds reduced the viscosity of the mAb formulation by more than 30 %, with reduction achieved by the six test compounds exceeding that achieved by proline (Pro). A reduction in the viscosity of the formulation below the 20 mPas threshold was achieved either by combining two test compounds or by increasing the concentration of a single compound above 25 mM. An accelerated stability study showed similar stabilization effects regardless of whether the test compounds were used alone or in combination. The percentage of aggregates was below 5 % in most formulations. These viscosity-reducing and stabilization effects corresponded to the dynamic light scattering results, which indicated that the test compounds reduced the attractive forces between the mAb molecules.

{"title":"Additive effects of the new viscosity-reducing and stabilizing excipients for monoclonal antibody formulation","authors":"Monika Prašnikar , Maja Bjelošević Žiberna , Nika Kržišnik , Robert Roškar , Iztok Grabnar , Aleš Žula , Pegi Ahlin Grabnar","doi":"10.1016/j.ijpharm.2025.125451","DOIUrl":"10.1016/j.ijpharm.2025.125451","url":null,"abstract":"<div><div>The subcutaneous administration of biopharmaceuticals is advantageous over intravenous administration, particularly with regard to improved patient compliance. However, in highly concentrated protein formulations lower viscosity of the formulation and stability of the protein is difficult to achieve. One approach involves using the viscosity-reducing excipients to diminish the interactions between protein molecules. In this context, the main objective of the study was to develop an optimal formulation for a model monoclonal antibody (mAb) and to evaluate new test compounds as viscosity-reducing agents. The test compounds were investigated both individually at increasing concentrations up to 200 mM and in combinations for their viscosity-reducing effect. Our results showed that all individual test compounds reduced the viscosity of the mAb formulation by more than 30 %, with reduction achieved by the six test compounds exceeding that achieved by proline (Pro). A reduction in the viscosity of the formulation below the 20 mPas threshold was achieved either by combining two test compounds or by increasing the concentration of a single compound above 25 mM. An accelerated stability study showed similar stabilization effects regardless of whether the test compounds were used alone or in combination. The percentage of aggregates was below 5 % in most formulations. These viscosity-reducing and stabilization effects corresponded to the dynamic light scattering results, which indicated that the test compounds reduced the attractive forces between the mAb molecules.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"674 ","pages":"Article 125451"},"PeriodicalIF":5.3,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596894","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}

引用次数: 0

Physical stability of bevacizumab solutions for intravitreal injections: Influence of conditioning material and storage conditions

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2025-03-08 DOI: 10.1016/j.ijpharm.2025.125453

Joëlle Claves , Philip Chennell , Christelle Blavignac , Valérie Sautou

The treatment of numerous retinal pathologies requires the use of intravitreal medications administered and compounded in medical 3-piece syringes. Particle formation influenced by storage conditions is a source of concern as it can have clinical impacts such as endophtalmitis or reduced visual acuity. The aim of this work was therefore to investigate and compare the physical stability of bevacizumab stored in syringes made of polypropylene lubricated with silicone oil (PP-SOL) or Cyclic Olefin Copolymer with crosslinked silicone at the surface of the barrel (COC-CLS). 0.2 mL of bevacizumab solutions were conditioned in both syringes types and the physical stability and particles or aggregate generation was followed after 3 days, 1 month and 3 months of storage, under three different storage conditions: refrigerated temperature (5 ± 3 °C), with or without mechanical stress after the storage period to simulate user manipulations before patient administration, and heat stress temperature (35 ± 2 °C). Particle counting, dynamic light scattering, size exclusion chromatography, size diffusion by taylor dispersion analysis, Fourier transform infrared spectroscopy, scanning electron microscopy and microanalysis X and calculated aggregation index via UV visible absorption were performed on the samples. Overall, the COC-CLS syringes generated less particles than the PP-SOL ones, in particular when submitted to a mechanical stress. The physical stability of the bevacizumab solutions was superior in COC-CLS syringes than in PP-SOL syringes.

{"title":"Physical stability of bevacizumab solutions for intravitreal injections: Influence of conditioning material and storage conditions","authors":"Joëlle Claves , Philip Chennell , Christelle Blavignac , Valérie Sautou","doi":"10.1016/j.ijpharm.2025.125453","DOIUrl":"10.1016/j.ijpharm.2025.125453","url":null,"abstract":"<div><div>The treatment of numerous retinal pathologies requires the use of intravitreal medications administered and compounded in medical 3-piece syringes. Particle formation influenced by storage conditions is a source of concern as it can have clinical impacts such as endophtalmitis or reduced visual acuity. The aim of this work was therefore to investigate and compare the physical stability of bevacizumab stored in syringes made of polypropylene lubricated with silicone oil (PP-SOL) or Cyclic Olefin Copolymer with crosslinked silicone at the surface of the barrel (COC-CLS). 0.2 mL of bevacizumab solutions were conditioned in both syringes types and the physical stability and particles or aggregate generation was followed after 3 days, 1 month and 3 months of storage, under three different storage conditions: refrigerated temperature (5 ± 3 °C), with or without mechanical stress after the storage period to simulate user manipulations before patient administration, and heat stress temperature (35 ± 2 °C). Particle counting, dynamic light scattering, size exclusion chromatography, size diffusion by taylor dispersion analysis, Fourier transform infrared spectroscopy, scanning electron microscopy and microanalysis X and calculated aggregation index via UV visible absorption were performed on the samples. Overall, the COC-CLS syringes generated less particles than the PP-SOL ones, in particular when submitted to a mechanical stress. The physical stability of the bevacizumab solutions was superior in COC-CLS syringes than in PP-SOL syringes.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"674 ","pages":"Article 125453"},"PeriodicalIF":5.3,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596905","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}

引用次数: 0