Drug Development and Industrial Pharmacy最新文献

{"title":"Recent advances in cationic material integration for enhanced antimicrobial formulations.","authors":"Sara Salatin, Shirin Ahmadi, Parvin Abedi Ghobadloo, Maryam Azarfarin, Samin Hamidi","doi":"10.1080/03639045.2026.2680188","DOIUrl":"10.1080/03639045.2026.2680188","url":null,"abstract":"<p><strong>Objective: </strong>To review recent advances in cationic antimicrobial systems - including surfactants, polymers, peptides, quaternary ammonium-based materials, and ionic-liquid-derived agents - and to summarize emerging strategies aimed at combating antibiotic-resistant bacteria.</p><p><strong>Significance of review: </strong>Cationic antimicrobial compounds provide a promising alternative to traditional antibiotics due to their membrane-disruptive action mediated by electrostatic interactions. This mechanism enables broad-spectrum activity while reducing the potential for resistance development.</p><p><strong>Key findings: </strong>A comprehensive evaluation of recent literature reveals substantial progress across multiple cationic antimicrobial platforms. Enhanced surfactants with improved membrane-disrupting efficiency, advanced cationic polymer architectures with greater biocompatibility, and engineered antimicrobial peptides (AMPs) with tunable properties have been reported. Furthermore, quaternary ammonium-based polymeric systems and rapidly expanding ionic-liquid antimicrobials demonstrate significant potential for diverse therapeutic and material applications.</p><p><strong>Conclusions: </strong>Cationic antimicrobial agents are advancing through varied chemical designs and formulation strategies, offering effective tools against resistant bacterial strains. Continued innovation across surfactant, polymer, peptide, and ionic-liquid systems highlights their increasing promise for both clinical and industrial implementation.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"1443-1461"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148028152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and characterization of olopatadine and verbascoside-loaded thermoresponsive <i>in situ</i> gels for ocular drug delivery: a factorial design approach for allergic conjunctivitis.","authors":"Heybet Kerem Polat, Tuğba Çopur, Esra Pezik, Yasin Turanlı, Nasıf Fatih Karakuyu, Esra Köngül, Sedat Ünal, Sefa Gözcü, Emine Sarman","doi":"10.1080/03639045.2026.2679187","DOIUrl":"10.1080/03639045.2026.2679187","url":null,"abstract":"<p><strong>Objective: </strong>Allergic conjunctivitis is one of the most prevalent conditions affecting the eyes, and various medications are used in its treatment. In this study, olopatadine and verbascoside were used in combination.</p><p><strong>Methods: </strong>A factorial design was employed to evaluate the effects of Poloxamer 407 and sodium alginate. The impact of polymer concentration on parameters such as viscosity, gelation time, mucoadhesion, pH, and gelation temperature - considered indicators of ideal formulations - was assessed.</p><p><strong>Results: </strong>The optimal formulation, determined through the factorial design, included 0.5% sodium alginate and 20% poloxamer 407. The obtained values were viscosity at 25 °C = 7451.8 cP, viscosity at 35 °C = 11367.3 cP, pH = 7.12, gelation temperature = 30 °C, gelation time = 52 s, and mucoadhesion = 0.301 N. Cytotoxicity tests on ARPE-19 and L929 cells, along with irritation studies, indicated acceptable safety profiles. <i>In vitro</i> release tests demonstrated an initial burst release of verbascoside and olopatadine during the first 2 h, followed by a controlled release over the subsequent 8 h. Mathematical analysis of the release kinetics revealed a good fit with the Weibull model. No adverse effects were observed in rats during Draize's <i>in vivo</i> test.</p><p><strong>Conclusions: </strong>Consequently, the drug-loaded <i>in situ</i> gel formulation may be a promising option for treating allergic conjunctivitis.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"1561-1578"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148053238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, optimization, and evaluation of ferulic acid-loaded cubosomal cream for enhanced topical delivery and anti-hyperpigmentation efficacy.","authors":"Rutuja Vinchurkar, Ashwin Kuchekar","doi":"10.1080/03639045.2026.2692051","DOIUrl":"10.1080/03639045.2026.2692051","url":null,"abstract":"<p><strong>Objective: </strong>The goal of this study was to create and optimize a topical cream based on cubosomes for improved dermal delivery and stability of ferulic acid, a strong antioxidant with anti-hyperpigmentation properties that is limited by low photostability and skin permeability.</p><p><strong>Significance: </strong>Improving the stability of ferulic acid and regulating its skin distribution is crucial for its successful application in cosmeceutical formulations. Cubosomal nanocarriers offer a viable way to enhance photostability, solubility, and sustained release, improving therapeutic efficacy while preserving skin safety.</p><p><strong>Methods: </strong>Glyceryl monooleate and Poloxamer 407 were used to create ferulic acid-loaded cubosomes. The effects of almond oil and Sepineo P600 on viscosity and drug content were assessed using the Box-Behnken design to optimize cream formulation. Particle size analysis, entrapment efficiency, Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and rheological investigations were all part of the characterization. To clarify release mechanisms, kinetic models were fitted to <i>in vitro</i> release data. Tyrosinase inhibition studies evaluated the effectiveness of anti-hyperpigmentation, while MTT and RT-PCR assays were used to assess biocompatibility.</p><p><strong>Results: </strong>The optimized formulation developed nanosized particles with thixotropic flow behavior, skin-compatible pH, and high entrapment efficiency. Diffusion-controlled delivery was indicated by release following first-order and Higuchi kinetics, although super case-II transport was suggested by Korsmeyer-Peppas analysis (<i>n</i> = 1.105). The cream showed moderate tyrosinase inhibition, TNF-α expression suppression, and non-cytotoxic behavior.</p><p><strong>Conclusion: </strong>Ferulic acid's potential as a safe and efficient cosmeceutical for skin-brightening applications is supported by the cubosomal cream's significant improvements in solubility, photostability, and prolonged dermal application.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"1594-1611"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148276500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analytical quality by design (AQbD)-based RP-HPLC method development and validation for concurrent determination of meloxicam and chlorhexidine in a novel dental <i>in-situ</i> gel for odontalgia.","authors":"Shiv Kumar, Nitasha Chauhan, Shruti Chopra, Amit Bhatia","doi":"10.1080/03639045.2026.2686259","DOIUrl":"10.1080/03639045.2026.2686259","url":null,"abstract":"<p><strong>Objective: </strong>Odontalgia (Tooth pain) involves inflammation and infection, requiring anti-inflammatory and antibacterial agents to manage pain. Conventional gels containing NSAIDs, topical anesthetics, and antibacterial agents, individually or in combination, are not very effective due to rapid saliva washout, thereby necessitating frequent re-dosing.</p><p><strong>Significance: </strong>As there are no oral <i>in-situ</i> gels containing anti-inflammatory and antibacterial agents available in the market for odontalgia, an <i>in-situ</i> gel containing meloxicam (prostaglandin inhibitor), thereby providing an anti-inflammatory effect, and chlorhexidine (antibacterial) was formulated for localized dual-action and prolonged contact at the targeted area. As there are no reported HPLC methods for the simultaneous estimation of meloxicam and chlorhexidine, an analytical quality-by-design-based reverse-phase high-performance liquid chromatography method was developed for the simultaneous quantification of both drugs in the formulated <i>in-situ</i> gel.</p><p><strong>Methods: </strong>Taguchi screening design analyses the influence of key chromatographic parameters on method performance. A Box-Behnken design was used to generate the trial runs. The final method utilized a Cosmosil 5 C₁₈-MS-II column with an isocratic mobile phase consisting of an aqueous phase containing 0.025% orthophosphoric acid and acetonitrile in 20:80% v/v ratio, flow rate (1.0 mL/min), injection volume (10 μL) at a detection wavelength of 289 nm.</p><p><strong>Results: </strong>The developed method was validated as per ICH Q2(R1) guidelines. The assay value was calculated and found to be 98.53% for MLX and 99.02% for CHX.</p><p><strong>Conclusions: </strong>The validated method applied for the quantitative analysis of meloxicam and chlorhexidine in the formulated <i>in-situ</i> gel.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"1623-1638"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148204557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Solid dispersions: a review on instability, improvement methods, and future development directions.","authors":"Wenjuan Wang, Yurong Lin, Sheng Wang, Zhaoyang Zhang","doi":"10.1080/03639045.2026.2680189","DOIUrl":"10.1080/03639045.2026.2680189","url":null,"abstract":"<p><strong>Objective: </strong>To systematically review the structural characteristics, release mechanisms, and stability challenges of solid dispersions (SDs), identifying key determinants of physical instability and summarizing emerging stabilization strategies.</p><p><strong>Significance: </strong>This review compares various stabilization approaches, highlighting their optimal applications and limitations to support broader SD market translation.</p><p><strong>Results: </strong>The generational evolution, structural features, and characterization techniques of SDs are outlined, along with the spring-parachute dissolution mechanism. Four major drivers of physical instability are identified: preparation-related parameters, humidity-induced phase separation, kinetic factors, and thermodynamic factors. Recent stabilization strategies-including ternary SD systems, drug loading control, and <i>in vivo</i> performance enhancement-are discussed. Emerging physicochemical descriptors and predictive models for rational formulation design are also summarized.</p><p><strong>Conclusion: </strong>SD technology remains critical for improving bioavailability of poorly water-soluble drugs, but broader translation is limited by system-dependent stability, inefficient excipient screening, high-dose formulation challenges, and limited predictive dissolution models. Future progress requires integrating formulation design, process engineering, and predictive modeling, including multifunctional polymers, advanced manufacturing (e.g. hot-melt extrusion), and digital tools based on molecular simulation and AI. Establishing biorelevant evaluation systems and robust <i>in vitro</i>-<i>in vivo</i> correlation (IVIVC) models is essential to bridge laboratory research and clinical application.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"1462-1476"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148013676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic and dissolution profiling of tadalafil formulated with SNEDDS and β-cyclodextrin in fast-dissolving tablets.","authors":"Cyril Jose, Sankalp Gharat, Afiya Baig, Pratibha Pilgaokar, Munira Momin","doi":"10.1080/03639045.2026.2675467","DOIUrl":"10.1080/03639045.2026.2675467","url":null,"abstract":"<p><p>One of the main challenges in the oral administration of tadalafil is its low water solubility, which limits its bioavailability. The research aims for enhancement of solubility and bioavailability for tadalafil, through comparing effectiveness for inclusion complex of Beta-cyclodextrin (β-CD) with self-nanoemulsifying drug delivery system (SNEEDS). Both approaches were further formulated into fast-dissolving tablets (FDTs) to achieve rapid onset of action. Dissolution studies demonstrated superior drug release from both systems compared to the marketed product, with SNEEDS showing 97.54 ± 1.76% release in 30 min and the β-CD complex exhibiting 92.47 ± 1.23% release in 15 min. SNEDDS tablets showed significantly improved dissolution compared to β-CD-tadalafil complexes. In pharmacokinetic studies on Wistar rats, SNEEDS resulted in a higher AUC of 4420.6 mcg/ml.hr, C-max of 3.95 mcg/ml, and a faster T-max of 4 h, indicating enhanced bioavailability in contrast with both the β-CD complexes and the marketed product. The lipophilic system (SNEEDS) was superior to the hydrophilic system (β-CD inclusion complex) in enhancing tadalafil bioavailability. Despite the lower AUC of developed β-CD complex compared to marketed formulation, increased C-max and faster T-max suggested a rapid onset of action and maximum efficacy. In conclusion, the developed lipophilic system-SNEEDS, significantly enhanced tadalafil bioavailability compared to both the hydrophilic system and the marketed product. The optimized SNEDDS formulation exhibited <b>significantly higher dissolution</b> compared with the β-cyclodextrin complex and marketed tablet. This study demonstrates the possibilities of innovative drug delivery systems, especially the lipophilic SEEDS, to address the difficulties related with poorly water-soluble drugs, offers promising avenue to enhance therapeutic efficacy.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"1477-1493"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Naringenin-loaded niosomal vaginal <i>in situ</i> gel: preclinical study in polycystic ovary syndrome-induced female Wistar rats.","authors":"Anvitha Welda Sequeira, Kishori P Sutar, Prakash R Biradar, Sahil Naik, Dsouza Kallis Xavier, Arun Jadhav, Sankalp S Sammasagi","doi":"10.1080/03639045.2026.2675474","DOIUrl":"10.1080/03639045.2026.2675474","url":null,"abstract":"<p><strong>Aim: </strong>This study aims to develop and assess Naringenin-loaded niosomal vaginal <i>in situ</i> gel for the effective management of Polycystic Ovary Syndrome. The objectives include enhancing drug permeation, ensuring sustained release and mitigating the oral side effects associated with naringenin.</p><p><strong>Method: </strong>Naringenin-loaded niosomes were formulated by ethanol injection method and a 3³Box-Behnken design (DESIGN EXPERT^® Software) with five center points was generated, yielding 17 experimental runs. They were characterized for globule size, percent entrapment efficiency, zeta potential, and polydispersity index. The optimized batch was incorporated into the <i>in situ</i> gel. Vaginal irritancy and <i>in vivo</i> studies were conducted in female Wistar rats to evaluate the therapeutic efficacy of the prepared formulation in the treatment of Polycystic Ovary Syndrome.</p><p><strong>Results: </strong>An 18% concentration of Pluronic F-127 was identified as optimal for gel formulation, and various evaluations, including <i>in vitro</i> drug release, diffusion studies, <i>in vivo</i> vaginal irritancy, histopathological analysis and short-term stability studies, were performed. The optimized niosomal formulation exhibited a vesicle size of 158.1 nm, an entrapment efficiency of 71.68%, a zeta potential of -28.6 mV and a drug content of 70.79 ± 1.95%. Transmission Electron Microscopy confirmed the nanoscale globule size, while the <i>in vitro</i> drug release rate for the niosomal formulation was 74.104%. The gel showed a viscosity range from 192.71 ± 1.23 cps to 1756.43 ± 7.46 cps as the temperature increased from 25 ± 2.0 °C to 38 ± 2.0 °C. <i>In vitro</i> diffusion studies showed 84.67% drug release. <i>In vivo</i> administration of the Naringenin loaded niosomal vaginal gel markedly lowered body weight and fasting blood glucose (<i>p</i> < 0.001) and reestablished hormonal, lipid, and antioxidant homeostasis by decreasing serum testosterone, triglycerides, total cholesterol, and low-density lipoprotein, while elevating progesterone, high-density lipoprotein, superoxide dismutase, catalase, and glutathione levels along with a concurrent decline in malondialdehyde (<i>p</i> < 0.001). Histopathological findings demonstrated fewer cystic follicles, restored folliculogenesis, and normalized adipocyte structure, and vaginal irritancy assessments verified the formulation's safety and therapeutic effectiveness against mifepristone-induced Polycystic Ovary Syndrome. Short-term stability studies demonstrated the optimized formulation's stability at 4 °C.</p><p><strong>Conclusion: </strong>The Naringenin-loaded niosomal vaginal <i>in situ</i> gel offers significant potential in managing PCOS with enhanced drug delivery and safety profiles.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"1494-1515"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148101111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Smart drug delivery systems based on frictional stimulus-responsive mechanisms: principles and applications.","authors":"Wenjing Lv, Mei Lv, Qianqian Sun, Guofa Zhang, Yu Luo, Litao Wang","doi":"10.1080/03639045.2026.2680190","DOIUrl":"10.1080/03639045.2026.2680190","url":null,"abstract":"<p><strong>Objective: </strong>This review systematically summarizes the mechanisms and applications of friction as both endogenous and exogenous stimuli in drug delivery systems (DDSs).</p><p><strong>Significance: </strong>Intelligent DDS can respond to endogenous or exogenous stimuli to achieve accurate drug delivery, so it has become a hot spot in pharmaceutical research. Therefore, friction, as a novel physical stimulus, offers unique potential to overcome physiological barriers and improve targeted therapy, providing new strategies for DDS design.</p><p><strong>Method: </strong>This article systematically reviews the two forms of stimulation of friction in drug delivery and its mechanism. In terms of endogenous effects, the focus was on exploring the regulatory effects of physiological friction, such as biological friction shear, cellular micro friction, eyelid corneal friction, and joint friction on drug delivery, revealing how frictional stimulation triggers drug release or enhances targeting through mechanical signals. In terms of exogenous effects, the promoting mechanism of mechanical friction on transdermal DDSs and the intracellular drug delivery technology driven by frictional nanogenerators were analyzed.</p><p><strong>Results: </strong>This review outlines friction-triggered drug release mechanisms and their therapeutic potential, highlighting superior spatiotemporal precision for dynamic tissues over traditional systems, yet notes key translational challenges including parameter standardization and drug-device integration.</p><p><strong>Conclusions: </strong>Friction, as a unique endogenous/exogenous stimulus, enables highly precise drug delivery. Advancing clinical translation requires establishing biotribological quantitative models, developing responsive biomimetic materials, and promoting integrated 'drug‑device' development through multidisciplinary collaboration.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"1429-1442"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging trends and future directions in co-amorphous solid dispersions for BCS class II and IV drugs.","authors":"Himali Rohit, Jitendra Patel, Manisha Lalan","doi":"10.1080/03639045.2026.2675449","DOIUrl":"10.1080/03639045.2026.2675449","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this review is to critically evaluate the potential of co-amorphous solid dispersions (CASDs) in improving the performance of poorly soluble active pharmaceutical ingredients (APIs).</p><p><strong>Significance: </strong>CASDs are being scoped in this review because limited aqueous solubility remains a persistent challenge in drug development, particularly for Biopharmaceutics Classification System (BCS) Class II and IV drugs, where poor solubility restricts oral bioavailability and clinical translation.</p><p><strong>Key findings: </strong>This review highlights the mechanistic aspects underlying enhanced bioavailability, phase behavior, and key molecular interactions that support the effectiveness of CASDs. Evidence from case studies demonstrates the use of diverse <b>co-formers</b>, including amino acids, organic acids, other APIs, and novel systems such as poly (amino acids) and flavonoids. Preparation methods, with emphasis on green and continuous manufacturing approaches such as spray drying, thermal, and mechanical activation, are discussed alongside advanced spectroscopic and computational characterization techniques. Reported outcomes consistently show improvements in solubility, dissolution, and pharmacokinetic properties, while regulatory perspectives and the application of Process Analytical Technology (PAT) illustrate pathways toward clinical adoption.</p><p><strong>Conclusion: </strong>CASDs represent a versatile platform with implications for personalized medicine, artificial intelligence (AI)-driven formulation design, and multifunctional <b>co-formers</b> though challenges in stability, scalability, and regulatory navigation remain priorities for future research.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"1413-1428"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147980947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Boosting oral bioavailability of Icaritin and Piperine: a co-amorphous approach with molecular insights and performance validation.","authors":"Xiaoxian Yao, Weidong Ye, Pingfu Huang, Xiangming Fang","doi":"10.1080/03639045.2026.2677652","DOIUrl":"10.1080/03639045.2026.2677652","url":null,"abstract":"<p><strong>Purpose: </strong>To overcome the poor aqueous solubility limitations of Icaritin (ICT) and Piperine (PIP), which restrict their therapeutic potential, by developing a co-amorphous drug delivery system.</p><p><strong>Significance: </strong>The co-amorphous strategy presents a promising solution to enhance solubility, dissolution rate, and oral bioavailability of poorly water-soluble drug combinations, thereby improving their pharmaceutical applicability.</p><p><strong>Methods: </strong>The optimal 1:1 molar ratio of ICT-PIP was determined through <i>in vitro</i> anti-inflammatory evaluation and combination modeling. Molecular dynamics simulations were employed to investigate intermolecular interactions, while Powder X-Ray Diffraction (PXRD), Fourier Transform Infrared Spectroscopy (FT-IR), and Differential Scanning Calorimetry (DSC) analyses were used to confirm co-amorphous formation and characterize solid-state properties.</p><p><strong>Results: </strong>The ICT-PIP co-amorphous system demonstrated significantly improved solubility (3.5-fold for ICT, 3.7-fold for PIP) and intrinsic dissolution rate (2.0-fold for ICT and 1.8-fold for PIP) compared to crystalline forms. PXRD confirmed complete amorphization with no detectable crystalline peaks, FT-IR revealed intermolecular hydrogen bonding interactions between ICT and PIP, and DSC showed a single glass transition temperature (<i>T</i>_g) at 164.6 °C, confirming single-phase amorphous system formation. Pharmacokinetic studies revealed 1.6-fold and 1.4-fold enhancements in oral bioavailability for ICT and PIP, respectively. The system maintained excellent physical stability for six months under storage conditions.</p><p><strong>Conclusion: </strong>This study successfully developed a stable ICT-PIP co-amorphous system with superior solubility and bioavailability characteristics, demonstrating the effectiveness of co-amorphization as a viable strategy for optimizing the delivery of poorly soluble drug combinations.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"1546-1560"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147971301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}