International Journal of Pharmaceutics最新文献_第2页

Natural deep eutectic solvents (NADES) in drug delivery systems: Characteristics, applications, and future perspectives

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2025-03-28 DOI: 10.1016/j.ijpharm.2025.125509

Hui Li , Kaining Yang , Yumin Yang , Liqin Ding , Xiaoxia Li

{"title":"Natural deep eutectic solvents (NADES) in drug delivery systems: Characteristics, applications, and future perspectives","authors":"Hui Li , Kaining Yang , Yumin Yang , Liqin Ding , Xiaoxia Li","doi":"10.1016/j.ijpharm.2025.125509","DOIUrl":"10.1016/j.ijpharm.2025.125509","url":null,"abstract":"<div><div>Deep eutectic solvents (DESs) are a class of low-melting mixtures formed by the hydrogen-bond interactions between hydrogen bond acceptors (HBAs) and hydrogen bond donors (HBDs) in specific molar ratios. Their unique physicochemical properties enable DESs to significantly enhance drug solubility and permeability, while also serving as carriers to facilitate efficient drug delivery. A subclass of DESs, natural deep eutectic solvents (NADESs), is found in the metabolites of natural organisms, such as plants. With low toxicity and biodegradability, NADESs possess distinct advantages for applications in the pharmaceutical field.The therapeutic efficacy of drugs is often limited by imprecise release mechanisms, leading to the metabolism or degradation of a portion of the drug before it reaches the target site, thereby reducing its effectiveness. Moreover, many drugs exhibit poor solubility and stability, resulting in low efficiency during absorption and metabolism, which further diminishing their therapeutic impact. NADESs, with their excellent tunability and biocompatibility, have demonstrated great potential in drug delivery systems.This paper first provides an overview of the fundamental characteristics of NADESs, followed by a detailed summary of recent advancements and applications of NADESs across various administration routes, including transdermal, mucosal, and inhalation drug delivery. Finally, the paper explores the prospects of NADESs in novel drug delivery systems and proposes strategies for optimizing their performance to promote clinical applications.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"675 ","pages":"Article 125509"},"PeriodicalIF":5.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734790","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 self-assembly enzyme-like hydrogel with ROS scavenging and immunomodulatory capability for microenvironment-responsive wound healing acceleration

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2025-03-28 DOI: 10.1016/j.ijpharm.2025.125529

Xiaohui Jia , Yuhe Dong , Jihui Lu , Zhenyuan Yang , Ran Xu , Xiang Zhang , Jingyi Jiao , Zixuan Zhang , Yixuan Lin , Fuhao Chu , Penglong Wang , Tian Zhong , Haimin Lei

{"title":"A self-assembly enzyme-like hydrogel with ROS scavenging and immunomodulatory capability for microenvironment-responsive wound healing acceleration","authors":"Xiaohui Jia , Yuhe Dong , Jihui Lu , Zhenyuan Yang , Ran Xu , Xiang Zhang , Jingyi Jiao , Zixuan Zhang , Yixuan Lin , Fuhao Chu , Penglong Wang , Tian Zhong , Haimin Lei","doi":"10.1016/j.ijpharm.2025.125529","DOIUrl":"10.1016/j.ijpharm.2025.125529","url":null,"abstract":"<div><div>On-demand responsive hydrogels are a promising solution for effective wound management as they can adjust their properties in response to changes in the wound environment, allowing them to provide tailored support for the healing process. However, the conventional hydrogels may not fully meet the diverse demands of the intricate healing process. Herein, a novel glycyrrhizic acid (GA) based self-assembly hydrogel coordinated with copper and polyphenol (GCP hydrogel) was developed to exhibit triggered release behavior in response to the microenvironment. The GCP hydrogel coordinated with copper and protocatechuic acid (PA) and self-assembled with GA, also exhibits enzyme-like properties by mimicking the cascade process of superoxide dismutase (SOD) and catalase (CAT), effectively scavenging reactive oxygen species (ROS). Furthermore, the on-demand release of Cu<sup>2+</sup> at different stages of the wound healing process can not only enhance the antibacterial ability of methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) but also intelligently promote angiogenesis with outstanding biocompatibility. In addition, the GCP hydrogel effectively modulated the activity of macrophages in response to inflammatory stimuli, exhibiting remarkable anti-inflammatory abilities and promoting tissue regeneration. The multifunctional GCP hydrogel platform has the potential to create a dynamic microenvironment that is conducive to tissue regeneration, making it an ideal candidate for smart wound management.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"675 ","pages":"Article 125529"},"PeriodicalIF":5.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752544","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

3D printing of partially-coated floating systems for controlled release of drugs into the stomach

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2025-03-27 DOI: 10.1016/j.ijpharm.2025.125513

Marco Uboldi , Arianna Chiappa , Francesco Briatico-Vangosa , Alice Melocchi , Lucia Zema

{"title":"3D printing of partially-coated floating systems for controlled release of drugs into the stomach","authors":"Marco Uboldi , Arianna Chiappa , Francesco Briatico-Vangosa , Alice Melocchi , Lucia Zema","doi":"10.1016/j.ijpharm.2025.125513","DOIUrl":"10.1016/j.ijpharm.2025.125513","url":null,"abstract":"<div><div>This work focused on the development of a retentive drug delivery system (DDS) able to float in the gastric fluids and to ensure prolonged release of drugs over a pre-defined period of time, being then safely emptied from the stomach. To this end, the design step played a pivotal role. The device was thus devised to be composed of a polyvinyl alcohol-based matrix with a tapered geometry, which was partially coated with an insoluble layer of thermoplastic elastomer. This way, release of allopurinol (ALP), used as model drug, could occur only from the uncoated surfaces, while the peculiar geometry of the hydrophilic swellable/erodible matrix was intended to balance the increase in the diffusional path over time with a wider release area. In addition, the coating featured air pockets, whose volume was sized to compensate for the weight force of the DDS once immersed in gastric fluids, thus ensuring its long-lasting buoyancy. By easing the entrance of gastric fluids when the matrix is completely exhausted, such air pockets would also favor sinking and removal of the DDS from the pylorus. Given the multi-layered geometry of the final floating device, including hard-to-fabricate details (<em>e.g.</em> uncoated surfaces, voids), fused deposition modeling 3D printing was identified as the technique of choice for its effectiveness in manufacturing complex shapes. Various formulations were tested for fabricating both the inner matrix and the outer coating, assessing their thermo-mechanical properties, printability and release behavior. The gastro-retentive system demonstrated prolonged buoyancy (> 12 h) and a wide portfolio of ALP release performances, differing in rate and duration, which would make it a promising platform for personalized delivery of drugs in the upper gastrointestinal tract.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"675 ","pages":"Article 125513"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739943","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

Enhanced targeted cytotoxic and apoptotic effects of docetaxel by enzyme-mediated controlled release system based on cyclodextrin/maltogenic amylase.

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2025-03-27 DOI: 10.1016/j.ijpharm.2025.125533

Zahra Sattari, Simin Dadashzadeh, Soraya Shahhosseini, Reza H Sajedi

{"title":"Enhanced targeted cytotoxic and apoptotic effects of docetaxel by enzyme-mediated controlled release system based on cyclodextrin/maltogenic amylase.","authors":"Zahra Sattari, Simin Dadashzadeh, Soraya Shahhosseini, Reza H Sajedi","doi":"10.1016/j.ijpharm.2025.125533","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2025.125533","url":null,"abstract":"<p><p>A novel system has been developed for the controlled release of docetaxel (DTX), an anticancer agent, utilizing β-cyclodextrin (β-CD) and maltogenic amylase (MAase) as the cyclodextrinase (CDase). In this study, we describe the creation of a targeted drug delivery system by conjugating MAase to a glutamate-urea-lysine (EUK) mimetic dipeptide, which acts as a ligand specific to the prostate-specific membrane antigen (PSMA), a crucial target for prostate cancer treatment. The conjugation of MAase and EUK was facilitated by dextran, as confirmed by dynamic light scattering (DLS). Additionally, we prepared a β-CD-DTX inclusion complex, which was validated using UV-visible (UV-vis) spectrophotometry and Fourier-transform infrared (FT-IR) spectroscopy, resulting in an encapsulation efficiency of 31.43. In vitro studies indicated that the β-CD-DTX/MAase-EUK bioconjugate displayed enhanced cytotoxicity against LNCaP cells, which express high levels of PSMA, with a half-maximal inhibitory concentration (IC<sub>50</sub>) of 34 nM after 48 h significantly lower than the 60 nM IC<sub>50</sub> associated with the β-CD-DTX/MAase system. Flow cytometric analysis revealed that the bioconjugate notably increased apoptotic rates compared to alternative formulations, showing early apoptosis at 28.2 % and late apoptosis at 14.2 %. Furthermore, activation of caspase-3/7 was significantly heightened in LNCaP cells treated with the β-CD-DTX/MAase-EUK system. These results indicate that the targeted delivery system enhances the solubility and bioavailability of DTX, thereby improving its therapeutic efficacy against prostate cancer while mitigating systemic toxicity.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"125533"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742888","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

Screening and preparation of curcumin nano-formulations combined with dissolving microneedles on the application in the effective treatment of psoriasis

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2025-03-27 DOI: 10.1016/j.ijpharm.2025.125528

Peng Xu , Kun Xu , Jiayin Li , Aoxue Liu , Wei Xiao , Lin Sun

{"title":"Screening and preparation of curcumin nano-formulations combined with dissolving microneedles on the application in the effective treatment of psoriasis","authors":"Peng Xu , Kun Xu , Jiayin Li , Aoxue Liu , Wei Xiao , Lin Sun","doi":"10.1016/j.ijpharm.2025.125528","DOIUrl":"10.1016/j.ijpharm.2025.125528","url":null,"abstract":"<div><div>Psoriasis, a prevalent immunoinflammatory skin condition, is characterized by abnormal skin thickening, which complicates traditional topical drug delivery and hinders drug penetration. Our goal is to enhance the efficacy of psoriasis treatment by developing a transdermal drug formulation. Microneedles (MNs) can improve treatment outcomes by increasing the absorption of topical medications through skin penetration. Curcumin (Cur), a natural anti-inflammatory, antioxidant, and immunomodulatory small molecule with water-insoluble properties, shows promise for psoriasis relief. In this research, three Cur nano-formulations (NFs) were screened and prepared using antisolvent and ethanol injection methods, with one being dispersed into hyaluronic acid (HA) dissolving MNs. A transdermal nano-MNs delivery system was constructed using a double-layer centrifugation technique. This co-delivery system overcame Cur’s solubility issues, poor absorption, and instability, allowing targeted and efficient delivery of Cur-NFs to the skin without being hindered by the skin barrier. <em>In vitro</em> studies demonstrated that Cur-NF dissolving MNs possess adequate mechanical properties for skin implantation, exhibit rapid dissolution, and achieve an effective drug release rate of 73 % within 6 h. Pharmacodynamic evaluations demonstrated that the MNs system effectively ameliorated key psoriatic skin manifestations. Notably, MNs treatment significantly reduced the Psoriasis Area and Severity Index (PASI) score from 12.0 ± 0.0 (model group) to 4.7 ± 0.5 (<em>p</em> < 0.05), alongside a marked suppression of pro-inflammatory cytokines, including TNF-α, IL-17, IL-22, and IL-23, compared to untreated psoriatic controls. Therefore, the composite dissolving MNs delivery system loaded with Cur-NFs represents a promising approach for psoriasis treatment.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"675 ","pages":"Article 125528"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734791","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

Development and adhesion evaluation of transdermal rotigotine patches utilizing 3D-printed skin-mimicking substrate, solid-state NMR, and ATR-FTIR techniques.

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2025-03-27 DOI: 10.1016/j.ijpharm.2025.125522

Arvind Bagde, Keb Mosley-Kellum, Sungsool Wi, Nisarg Modi, Satyanarayan Dev, Mandip Singh

{"title":"Development and adhesion evaluation of transdermal rotigotine patches utilizing 3D-printed skin-mimicking substrate, solid-state NMR, and ATR-FTIR techniques.","authors":"Arvind Bagde, Keb Mosley-Kellum, Sungsool Wi, Nisarg Modi, Satyanarayan Dev, Mandip Singh","doi":"10.1016/j.ijpharm.2025.125522","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2025.125522","url":null,"abstract":"<p><p>Transdermal rotigotine patches, used to treat parkinson's disease, often face challenges in maintaining adequate adhesion, which is crucial for effective drug delivery. Adhesion performance is influenced by environmental conditions such as humidity and temperature, as well as skin characteristics like wrinkles and micro-delaminations that vary with age and sex. Standard adhesion tests using stainless steel (SS) substrates do not accurately mimic human skin, leading to overestimated adhesion strength. This study developed rotigotine matrix transdermal formulations with silicone pressure sensitive adhesive (PSA) and evaluated their adhesion properties at 32 ± 1°C and 75 ± 5 % RH in a stability chamber. Moisture uptake over 24 h was measured using solid-state nuclear magnetic resonance (SSNMR) spectroscopy and attenuated total reflectance-fourier transform infrared- (ATR-FTIR) spectroscopy. Adhesion tests, including probe tack and peel, were performed on SS and 3D-printed acrylonitrile butadiene styrene (ABS) substrates designed with micro-delaminations and wrinkles to simulate skin conditions. In vitro permeation testing (IVPT) studies demonstrated a flux of 10.48 ± 0.61 and 10.03 ± 0.57 μg/h/cm<sup>2</sup> for formulations with and without mannitol, respectively. SSNMR and ATR-FTIR revealed significant moisture uptake, contributing to adhesion loss. Adhesion forces were significantly lower on ABS compared to SS, with further reductions observed on wrinkled and micro-delaminated surfaces, indicating that SS substrates overestimate adhesion results. This is the first study to combine SSNMR and skin-mimetic substrates for analyzing adhesion loss in transdermal patches, highlighting the potential of moisture-resistant agents like mannitol to enhance patch performance.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"125522"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742873","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

Development of a stable fixed-dose combination of Montelukast Sodium and Levocetirizine Dihydrochloride using multi-layering API coating technology.

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2025-03-26 DOI: 10.1016/j.ijpharm.2025.125527

Dong-Joon Oh, Seo-Young Shin, Chae-Yong Lim, Yu-Byeong Chae, Jung-Ho Yang, Sung-Joo Hwang

{"title":"Development of a stable fixed-dose combination of Montelukast Sodium and Levocetirizine Dihydrochloride using multi-layering API coating technology.","authors":"Dong-Joon Oh, Seo-Young Shin, Chae-Yong Lim, Yu-Byeong Chae, Jung-Ho Yang, Sung-Joo Hwang","doi":"10.1016/j.ijpharm.2025.125527","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2025.125527","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to develop a combination drug containing Montelukast Sodium and Levocetirizine Dihydrochloride using Multi-Layering API Coating Technology (M-LAC Tech) to prevent chemical interactions, enhance stability, and enable sequential drug release.</p><p><strong>Methods: </strong>A core tablet containing Montelukast Sodium was prepared, followed by a barrier coating layer. Levocetirizine Dihydrochloride was then applied as a drug coating over the barrier layer, ensuring complete separation of the two drugs. M-LAC Tech effectively prevents chemical interactions, overcoming the limitations of conventional single-layer and bilayer tablets. An outer coating was added to protect against environmental factors, resulting in a multi-layered film-coated tablet with improved stability and drug release characteristics.</p><p><strong>Results: </strong>The developed tablet reduced size by 50% compared to bilayer tablets, improving patient compliance. The barrier coating effectively prevented drug interactions, ensuring stability, while sequential drug release reduced AUC variability and shortened T<sub>max</sub>, enhancing absorption and efficacy. Compared to the reference \"tablet-in-capsule\" formulation, which releases both drugs simultaneously, the M-LAC Tech tablet demonstrated superior pharmacokinetic properties through controlled sequential release.</p><p><strong>Conclusion: </strong>M-LAC Tech enabled the stable incorporation of two drugs in a single dosage form, achieving the smallest tablet size among similar formulations. The technology's ability to block drug interactions and optimize release profiles provides significant clinical advantages. These findings highlight the potential of M-LAC Tech in advancing combination drug development.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"125527"},"PeriodicalIF":5.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742885","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

Comparative analysis of tablet dissolution behavior: Batch vs. Continuous direct compression

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2025-03-26 DOI: 10.1016/j.ijpharm.2025.125498

Kensaku Matsunami , Alexander Ryckaert , Hanne Verrecas , Ana Filipa Tavares da Silva , Andrew Anderson , Håkan Wikström , Melanie Dumarey , James Mann , Thomas De Beer , Valérie Vanhoorne , Ashish Kumar

{"title":"Comparative analysis of tablet dissolution behavior: Batch vs. Continuous direct compression","authors":"Kensaku Matsunami , Alexander Ryckaert , Hanne Verrecas , Ana Filipa Tavares da Silva , Andrew Anderson , Håkan Wikström , Melanie Dumarey , James Mann , Thomas De Beer , Valérie Vanhoorne , Ashish Kumar","doi":"10.1016/j.ijpharm.2025.125498","DOIUrl":"10.1016/j.ijpharm.2025.125498","url":null,"abstract":"<div><div>Continuous manufacturing offers advantages over traditional batch methods, including agility, efficiency, and sustainability. However, transitioning to continuous manufacturing in process development is challenging due to the need for early adoption of industrial-scale equipment. Conversely, batch processes require extensive scale-up studies before commercialization, which continuous processes can avoid. A more efficient approach is to use batch trials in early development to design formulations and processes for continuous manufacturing, requiring assessment of their transferability.</div><div>This study compares the dissolution behavior of immediate-release tablets manufactured via batch and Continuous Direct Compression (CDC), using ibuprofen, a BCS Class II drug. A Design of Experiments (DoE) approach varied formulation properties and tensile strength, with three methods: i) similarity factor ([f2]), ii) Weibull model fitting and Partial Least Squares (PLS) regression, and iii) Gaussian Process Regression (GPR) to assess the transferability of batch trial data and dissolution models for CDC formulation and process design.</div><div>Dissolution profiles were identical between batch and CDC trials when formulations and tensile strength matched, with differences observed only due to deviations in actual tensile strength. The PLS model indicated minimal impact of operational modes on dissolution behavior. The GPR model based only on batch trial data predicted CDC dissolution profiles with a mean <em>R</em><sup>2</sup> of 0.910 and RMSE of 4.88%. Overall, the transferability analysis confirmed the predictive capacity of the developed model using batch trial data on the dissolution behavior of tablets manufactured via a CDC line.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"675 ","pages":"Article 125498"},"PeriodicalIF":5.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739361","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

Intraluminal enzymatic hydrolysis of API and lipid or polymeric excipients

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2025-03-26 DOI: 10.1016/j.ijpharm.2025.125489

Zahari Vinarov , Anette Müllertz , Hristina Mircheva , Yann Le Gouar , Olivia Menard , Sharon Pradeep Kumar , Amrit Paudel , Didier Dupont , Patrick Augustijns

{"title":"Intraluminal enzymatic hydrolysis of API and lipid or polymeric excipients","authors":"Zahari Vinarov , Anette Müllertz , Hristina Mircheva , Yann Le Gouar , Olivia Menard , Sharon Pradeep Kumar , Amrit Paudel , Didier Dupont , Patrick Augustijns","doi":"10.1016/j.ijpharm.2025.125489","DOIUrl":"10.1016/j.ijpharm.2025.125489","url":null,"abstract":"<div><div>The role of intraluminal enzymes for the hydrolysis of active pharmaceutical ingredients (API), prodrugs and pharmaceutical excipients will be reviewed. Carboxylesterases may hydrolyze ester-based API, prodrugs and ester-bond containing polymer excipients, whereas lipases digest lipid formulation excipients, such as mono-, di- and triglycerides. To clarify the conditions that should be mimicked when designing <em>in vitro</em> studies, we briefly review the upper gastrointestinal physiology and provide new data on the inter-individual variability of enzyme activities in human intestinal fluids. Afterwards, the methodology for studying enzymatic hydrolysis of API, prodrugs, lipid and polymeric excipients, as well as the main results that have been obtained, are summarized. <em>In vitro</em> digestion models used to characterize lipid formulations are well described, but data about the hydrolysis of lipid excipients (including surfactants) has been scarce and contradictory. Data on API and prodrug hydrolysis by esterases is available; however, inconsistent use of enzyme types and concentrations limits structure-stability relationships. Hydrolysis of polymer excipients in the lumen has not been significantly explored, with only qualitative data available for cellulose derivates, polyesters, starches, etc. Harmonization of the methodology is required in order to curate larger enzymatic hydrolysis datasets, which will enable mechanistic understanding and theoretical prediction.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"675 ","pages":"Article 125489"},"PeriodicalIF":5.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742895","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

A simplified method to interpret the mechanism of drug release from thin polymeric films by drug diffusivity measurements.

IF 5.3 2区医学

International Journal of Pharmaceutics Pub Date : 2025-03-26 DOI: 10.1016/j.ijpharm.2025.125491

Karin Korelc, Martina M Tzanova, Anette Larsson, Mario Grassi, Massimiliano Pio Di Cagno, Ingunn Tho

{"title":"A simplified method to interpret the mechanism of drug release from thin polymeric films by drug diffusivity measurements.","authors":"Karin Korelc, Martina M Tzanova, Anette Larsson, Mario Grassi, Massimiliano Pio Di Cagno, Ingunn Tho","doi":"10.1016/j.ijpharm.2025.125491","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2025.125491","url":null,"abstract":"<p><p>Drug-polymer interactions and their respective affinities provide vital information for developing any polymer-containing drug delivery system, such as oral films. This paper offers a simplified method to estimate the effects of interactions between the drug and polymers in corresponding film formulations using a recently developed Fickian diffusion-based methodology. Poly(vinyl alcohol-co-vinyl acetate) (PVA/PVAc) copolymers were used as film matrix formers. To systematically vary the hydrophilicity of the polymer and drug, PVA/PVAc copolymers (monomer ratios 35:65, 50:50, 74:26, 88:12, 98:2) and model drugs, hydrochlorothiazide and caffeine (with a factor 1:30 in solubility) were used. Drug diffusivities determined in a polymer solution (5 % w/v) were compared to classical in vitro drug release from the films. The drug release rate from films containing copolymers with a lower VA/VAc ratio (35:65, 50:50, and 74:26) was significantly different for the two drugs in the first 30 min. It was found that this diffusivity method provided valuable guidance in assessing drug-polymer affinity, described as the average theoretical partition constant K<sub>m/w</sub> between the polymer solution and pure aqueous media. This partition constant could be correlated to the drug release rate and serve as a simple, easy, and inexpensive screening method to provide deeper mechanistic insight into drug release mechanisms. This would allow enhanced sustainability and accelerate the formulation development process by reducing resources needed for the development of film formulations.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"125491"},"PeriodicalIF":5.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742866","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