Drug Development and Industrial Pharmacy最新文献

{"title":"Polysaccharide-based suspensions: a novel pediatric-friendly formulation for administering furosemide through nasogastric tubes.","authors":"Luiza Gonçalves Soutier, Carla Suellen Gurski, Felipe Neme Ribeiro, Giovanna Araujo de Morais Trindade, Marcel Henrique Marcondes Sari, Thais Martins Guimarães, Roberto Pontarolo, Luana Mota Ferreira","doi":"10.1080/03639045.2026.2651289","DOIUrl":"10.1080/03639045.2026.2651289","url":null,"abstract":"<p><strong>Objective: </strong>Our study aimed to develop extemporaneous furosemide suspensions using a polysaccharide as the suspensor agent and to evaluate their stability and drug loss during tube administration.</p><p><strong>Significance: </strong>Extemporaneous oral furosemide liquid formulations are often necessary for managing neonatal cardiovascular disorders, as commercial formulations are typically limited to solid preparations. However, the practice involves syrup as the vehicle, and data on the stability of these formulations are missing.</p><p><strong>Methods: </strong>Suspensions were prepared by crushing tablets and using xanthan gum as a thickening agent, without the addition of sugar or preservatives. Samples were stored at room temperature, under refrigeration, and at 40 °C. Physicochemical stability was evaluated on days 0, 3, 5, and 7, assessing pH, density, sedimentation volume, redispersion time, and drug content. Drug quantification was performed using an adapted UV spectrophotometric method. Microbiological stability was evaluated on the same days following standard procedures for nonsterile preparations. <i>In vitro</i> simulations of nasogastric tube administration were conducted to determine potential drug loss.</p><p><strong>Results: </strong>The formulation maintained stable physicochemical properties over 7 days, with no sedimentation and a density of 1.2 g/mL. Drug content remained near 100%, and pH was around 6.0, with non-Newtonian behavior. Microbiological assessments confirmed conformity with microbial count limits and the absence of pathogens for seven days under refrigeration, at room temperature, and at 40 °C. After nasogastric tube administration, the losses were 13% and 14%.</p><p><strong>Conclusions: </strong>Oral furosemide suspensions prepared with xanthan gum exhibited satisfactory physicochemical and microbiological stability. These neonatal formulations show potential for the safe management of pediatric cardiovascular disorders.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"1-14"},"PeriodicalIF":2.2,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147510518","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":"AQbD-based UHPLC approach for quantification of everolimus residues in cleaning validation processes.","authors":"Jagdish Gohel, Ajay Patel, Rajendra Kotadiya","doi":"10.1080/03639045.2026.2654748","DOIUrl":"10.1080/03639045.2026.2654748","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to develop and validate a robust reverse-phase ultra-performance liquid chromatography (UHPLC) method for the quantification of everolimus residues on pharmaceutical manufacturing equipment surfaces, ensuring effective cleaning validation.</p><p><strong>Significance: </strong>Cleaning validation is a critical requirement in pharmaceutical manufacturing to prevent cross-contamination and ensure product integrity. The application of the Analytical Quality by Design (AQbD) framework enhances method robustness, reliability, and regulatory compliance while aligning with principles of sustainable and green analytical chemistry.</p><p><strong>Methods: </strong>Risk assessment tools and a central composite design were used to identify and control critical method parameters. Chromatographic separation was achieved using an Acquity UPLC BEH C18 column (50 mm × 2.1 mm; 1.7 μm) with a mobile phase consisting of acetonitrile and water (65:35% v/v) at a flow rate of 0.4 mL/min. The method was validated according to ICH Q2 (R2) guidelines.</p><p><strong>Results: </strong>The developed method demonstrated a rapid retention time of 1.57 min and excellent linearity over the concentration range of 0.4 to 3.0 μg/mL, with a correlation coefficient (R²) of 0.999. The limits of detection and quantification were found to be 0.100 μg/mL and 0.392 μg/mL, respectively. The method showed high specificity, precision (%RSD within acceptable limits), and recovery accuracy ranging from 91% to 100%.</p><p><strong>Conclusions: </strong>The developed method provides a sensitive, precise, and eco-friendly solution for the quantification of everolimus residues in cleaning validation processes. It fulfils regulatory expectations and is suitable for routine use in pharmaceutical quality control settings, reinforcing product safety and operational efficiency.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"1-17"},"PeriodicalIF":2.2,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147622102","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":"Albendazole-loaded chitosan nanoparticle conjugated with hyaluronic acid for the treatment of psoriasis.","authors":"Shrikanth Nair, Prabha Singh","doi":"10.1080/03639045.2026.2651296","DOIUrl":"10.1080/03639045.2026.2651296","url":null,"abstract":"<p><strong>Objective: </strong>To design and develop hyaluronic acid (HA) conjugated Albendazole (ABZ) loaded chitosan nanoparticles (HA-ABZ-CSNP) loaded hydrogel for the treatment of psoriasis.</p><p><strong>Significance: </strong>Albendazole (ABZ), a commonly used anti-parasitic drug, has garnered a lot of attention lately including anticancer and anti-psoriasis properties. Chitosan nanoparticle followed by conjugation with HA was formulated in hydrogel base making it an excellent strategy for targeting overexpressed CD44 receptor on psoriatic skin as well as alleviating the problems, such as dryness, itchiness associated with psoriasis.</p><p><strong>Methods: </strong>ABZ-CSNP was formulated by ionic gelation technique followed by conjugation with hyaluronic acid (HA) and was evaluated for particle size, zeta potential, entrapment efficiency, respectively. Developed HA-ABZ-CSNP were incorporated into hydrogel base and were evaluated for <i>in-vitro</i> drug release. <i>Ex-vivo</i> studies were performed. <i>In-vivo</i> studies were performed on Balb/c mice and tests, such as Psoriasis Area Severity Index (PASI), Spleen weight assessment, and histopathological studies were conducted.</p><p><strong>Results: </strong>Optimized HA-ABZ-CSNP showed a particle size of 170.1 ± 76.38 nm, zeta potential of 31.6 mV, and entrapment efficiency of 98.89%, respectively. Developed HA-ABZ-CSNP hydrogel showed a Korsemeyer and Peppas release model and an <i>in-vitro</i> release of 93.90 ± 32.50 % in around 24 h. <i>Ex-vivo</i> studies were conducted which showed 30.74 ± 13.65% in 24 h. <i>In-vivo</i> studies conducted on Balb/c mice showed reduced PASI, Spleen weight as well as reduced keratinocyte proliferation in histopathological studies.</p><p><strong>Conclusions: </strong>In conclusion, developed novel formulation of ABZ reduced keratinocyte proliferation making it a possible effective strategy in the management of psoriasis.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"1-15"},"PeriodicalIF":2.2,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147527573","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":"Degradation kinetics of apomorphine hydrochloride in buffered formulations and the effect of antioxidants.","authors":"Abeer M Al-Ghananeem, Sarah Baltzley, Azzam A Malkawi, Sai Hs Boddu","doi":"10.1080/03639045.2026.2652043","DOIUrl":"10.1080/03639045.2026.2652043","url":null,"abstract":"<p><strong>Introduction: </strong>Apomorphine (APO) is inherently unstable in aqueous solutions, as it forms auto-oxidation products. The study investigates the degradation kinetics of APO as the function of pH and evaluates the stabilizing effects of antioxidants (i.e. ascorbic acid (AA) and sodium metabisulfite (SMB)) on APO solution formulations.</p><p><strong>Significance: </strong>To understand combined impact of pH-adjustment, buffer concentrations and antioxidant addition on the degradation kinetics of APO.</p><p><strong>Methods: </strong>The degradation kinetics of APO in solutions and the antioxidant effect were investigated with a reversed-phase HPLC system. The influences of pH value on degradation of APO were studied in aqueous solutions. Stability studies were performed under a nitrogen blanket and protected from light to minimize oxidative and light-induced degradation and allow aqueous degradation in order to establish the pH-rate profile of APO in aqueous media.</p><p><strong>Results: </strong>APO in aqueous solution showed rapid degradation with pseudo-first-order kinetics at 25 °C. The log <i>k_o</i>-pH profile indicated that the optimal stability range for APO was at acidic pH values of 2.4-2.6. Degradation rate constants were determined for reactions run over pH values range of 2.0-8.0. The lowest molar buffer concentration used at 0.01 M, resulted in a more stable APO formulation. AA used at 1% as an antioxidant in APO formulation appeared to be superior against APO degradation with 97.4% of APO remaining, while 50% SMB formulation had the most APO degradation with 94.25% APO remaining after 6 months.</p><p><strong>Conclusion: </strong>The APO aqueous formulation at pH 2.4-2.6 with 1% AA is recommended to maximize stability and clinical tolerability.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"1-12"},"PeriodicalIF":2.2,"publicationDate":"2026-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147510475","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":"Folate-functionalized core-shell nanocarrier System for sustained and targeted delivery of <i>Saraca Indica</i> for breast cancer treatment.","authors":"Youssra Ragheb, Sarah Yahia, Rabab M El Sherif, Ibrahim M El-Sherbiny","doi":"10.1080/03639045.2026.2631660","DOIUrl":"10.1080/03639045.2026.2631660","url":null,"abstract":"<p><p><b>Background:</b> Targeted therapy plays a crucial role in minimizing the adverse effects of chemotherapy on normal cells by specifically directing therapeutics to cancerous tissues. <b>Objectives:</b> The purpose of this study is to develop a novel nanocarrier system based on components that work in harmony to achieve dual-targeted and efficient breast cancer (BC) therapy. <b>Methods:</b> The nanocarrier was successfully prepared using pluronic acid (PL), sodium hyaluronate (SH), and folate-conjugated chitosan (CS-FA) as core-shell nanoparticles (NPs) for delivering anticancer agent; <i>Saraca Indica</i> (SI) extract. CS-FA was chemically synthesized and then combined with SH to form the NPs' shell, coating SI-loaded self-assembled PL nanomicelles core. <b>Results:</b> The core-shell SI-loaded NPs (SINPs) possess stable shell, as indicated by their zeta-potential of +48 ± 2.3 mV and size of 224 ± 2.0 nm. The SI's loading was 47.3%. <i>In-vitro</i> release profile of SI from SINPs was sustained for 20-days. The SI free form exhibited IC₅₀ of 41.29 ± 2.89 µg/ml, while SINPs showed 30.04 ± 2.14 µg/ml, which ascertains the role of encapsulating SI in NPs in improving its cytotoxicity against MCF-7 BC cells. Fluorescent micrographs indicated that (CS-FA)-based NPs were significantly engulfed by MCF-7 cells as compared to CS NPs, suggesting that CS-FA-based NPs have enhanced therapeutic efficacy through endocytosis-mediated by folate receptors. The SINPs significantly reduced tumor volume in mice compared to free SI, demonstrating their potent anticancer activity, and confirming that SINPs can increase the SI's anticancer efficiency <i>via</i> targeted folate receptor pathways. <b>Conclusion</b>: The developed SINPs are a promising targeted nano-delivery system for SI toward an augmented BC treatment.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"763-779"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146178356","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":"Novel elastic nanovesicular hydrogel system: advancing metronidazole delivery for effective periodontitis management.","authors":"Arooj Komal, Naveed Ahmed, Muhammad Usman Khan, Fahim Hilal, Muhammad Ijaz Khan, Asim Ur Rehman","doi":"10.1080/03639045.2026.2619555","DOIUrl":"10.1080/03639045.2026.2619555","url":null,"abstract":"<p><strong>Objective: </strong>Periodontitis, characterized by chronic gingival inflammation driven by polymicrobial biofilm formation, presents a significant therapeutic challenge due to the inherent difficulty of antimicrobial penetration through the biofilm matrix and limited drug retention.</p><p><strong>Methods: </strong>To address these challenges, this study developed a metronidazole-loaded spanlastic-based mucoadhesive hydrogel (MTZ-SPLG) for direct intra-pocket delivery, designed to overcome biofilm barriers and prolong drug residence time. The spanlastics (SPL) formulation achieved optimal characteristics (93% EE, 0.168 PDI, 280.8 nm size) through Design Expert^® 13 optimization, utilizing Span 80 (15 mg/ml) and Tween 80 (6.5 mg/ml) with 4-min sonication in the ethanol injection process. FTIR analysis confirmed the absence of chemical interactions, while DSC and XRD demonstrated successful transformation of metronidazole (MTZ) from crystalline to amorphous form. The optimized metronidazole loaded spanlastics (MTZ-SPL) incorporated into a Carbopol^® hydrogel base, exhibited suitable intra-periodontal properties including homogeneity, appropriate pH, and optimal spreadability, with mucoadhesive strength of 2256.3 N/m².</p><p><strong>Results: </strong>In vitro studies at pH 6.8 revealed sustained drug release following Korsmeyer-Peppas model with Fickian diffusion, outperforming conventional MTZ formulations. The MTZ-SPLG formulation demonstrated superior antibacterial efficacy with the largest inhibition zones (29.0-30.5 mm), lowest MIC values (2.2-5.9 μg/mL), and highest biofilm inhibition (60-89%) and degradation (43.6-64.3%) across all tested pathogens. Despite lower permeation than MTZ-SPL, MTZ-SPLG achieved optimal tissue retention (81.6 μg/cm²).</p><p><strong>Conclusions: </strong>Based on our study findings, the formulation significantly reduced inflammation and demonstrated superior efficacy in periodontitis treatment.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"667-683"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146009147","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":"Quality by design-driven approach to develop a nanocarrier-based sulfasalazine topical system for rheumatoid arthritis management.","authors":"Ankit Raj, Pradip Nirbhavane, Himanshu Gandhi, Sachin Yadav, Atin Kalra, Satish Sardana","doi":"10.1080/03639045.2026.2630260","DOIUrl":"10.1080/03639045.2026.2630260","url":null,"abstract":"<p><strong>Objective: </strong>This study was conducted to improve the transdermal delivery of sulfasalazine (SSZ) by encapsulating it into the nanostructured lipid carrier (NLC)-based gel products.</p><p><strong>Methods: </strong>Sulfasalazine was loaded into NLCs through solvent diffusion evaporation method. Box-Behnken design (BBD) was used to optimize formulation variables such as lipid concentration, ethanol concentration, and ultrasonication time. The optimized NLCs were analyzed for particle size, polydispersity index (PDI), and entrapment efficiency (%EE), and then morphological analysis was performed using scanning electronic microscopy (SEM). The NLC dispersion was added to a 1% gel base of Carbopol 934. The developed gel formulation was assessed for its <i>in vitro</i> release, <i>ex vivo</i> skin permeation, and anti-inflammatory activity (BSA protein denaturation assay).</p><p><strong>Results: </strong>Optimized SSZ-NLCs had a mean particle size of 112.5 nm, PDI of 0.090, and EE of 89%. SEM ensured spherical and uniform particle morphology. The SSZ-NLC gel exhibited higher drug release (∼65.17% in 24 h) compared to the SSZ-conventional gel (∼25.73%). The <i>ex vivo</i> permeation exhibited higher skin permeation than conventional gel. The anti-inflammatory studies indicated concentration-dependent suppression of BSA denaturation with 77.2% inhibition at 5000 μg/mL.</p><p><strong>Conclusion: </strong>The developed gel formulation has shown desired characteristics to serve as a topical treatment of rheumatoid arthritis.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"750-762"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146164758","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":"Ultra-stabilized transethosomal gel for co-delivery of 5-fluorouracil and carvedilol: cytotoxicity and <i>in vivo</i> studies in skin cancer.","authors":"Prafull Shinde, Amit Page","doi":"10.1080/03639045.2026.2628014","DOIUrl":"10.1080/03639045.2026.2628014","url":null,"abstract":"<p><strong>Objective: </strong>Skin cancer is a widespread malignancy requiring advanced strategies to address poor skin permeation, drug resistance, and low local bioavailability. This study aimed to develop and evaluate 5-fluorouracil and carvedilol loaded transethosomal (FU-CVD-TEs) gel for enhanced targeted skin cancer therapy.</p><p><strong>Significance: </strong>Conventional topical treatments often show inadequate dermal penetration and retention. The dual-drug transethosomal platform offers a novel approach to improve permeation, achieve sustained release, and enhance synergistic anti-cancer effects, which has not been previously reported for this drug combination in melanoma therapy.</p><p><strong>Methods: </strong>FU-CVD-loaded transethosomes were prepared using Lipoid S100, Tween-80, polyvinyl alcohol, and ethanol. Vesicles were characterized using TEM, SEM, and atomic force microscopy (AFM). Optimized FU-CVD-TEs were incorporated into a Carbopol 934 with Poloxamer 188 hybrid gel and evaluated for rheology, dermatokinetics, and <i>in vitro</i> cytotoxicity in HaCaT cells. <i>In vivo</i> studies in Wistar rats assessed dermal deposition, tumor suppression, and skin tolerability.</p><p><strong>Results: </strong>FU-CVD-TEs showed high entrapment efficiency, nanoscale size, and sustained release following Higuchi kinetics (<i>R</i>² = 0.989). The hybrid gel displayed viscoelastic behavior. <i>In vitro</i> formulation enhanced ROS generation, induced G1-phase arrest and apoptosis, and showed significantly reduced IC₅₀. <i>In vivo</i> studies demonstrated markedly improved dermal deposition, strong tumor suppression, and excellent skin safety compared with conventional formulations.</p><p><strong>Conclusion: </strong>The FU-CVD-TEs hybrid gel enhanced cutaneous permeation, therapeutic efficacy, and tumor-regression potential while maintaining a favorable safety profile. This strategy represents a promising and effective approach for melanoma treatment, warranting further molecular and clinical investigations.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"701-719"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146164689","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":"Microfluidic-based intra-articular sustained release of triamcinolone acetonide microsphere-gel composite system.","authors":"Yuan Zhu, Yongqi Lv, Jiaqi Xu, Yingshu Feng, Caleb Kesse Firempong, Runfeng Wang, Haibing He, Guoqing Zhang, Hongfei Liu","doi":"10.1080/03639045.2026.2629611","DOIUrl":"10.1080/03639045.2026.2629611","url":null,"abstract":"<p><strong>Objective: </strong>This study presents a novel injectable microsphere-gel system for sustained intra-articular delivery of triamcinolone acetonide (TA) to treat osteoarthritis.</p><p><strong>Significance: </strong>This system aims to overcome the shortcomings of conventional TA suspensions, such as short joint residence time and significant systemic exposure, thereby improving therapeutic efficacy and safety for osteoarthritis treatment.</p><p><strong>Methods: </strong>TA-loaded polycaprolactone (PCL) microspheres (TA@PCL) were prepared using microfluidic technology under optimized conditions. The TA@PCL microspheres were incorporated into the cross-linked hyaluronic acid (CLHA) gel matrix to form an injectable composite (TA@PCL@CLHA), which was evaluated by <i>in vitro</i> studies (rheological property, stability, and drug release) and <i>in vivo</i> studies (plasma pharmacokinetics and drug retention in knee joints).</p><p><strong>Results: </strong>TA@PCL microspheres with uniform size (D₅₀ value of 61.4 ± 1.9 µm, span value of 0.075) and high encapsulation efficiency (87.2 ± 4.1%) were successfully prepared. The TA@PCL@CLHA composite exhibited excellent injectability (extrusion force of 12.1 ± 0.4 N) and physical stability over 90 days. <i>In vitro</i>, the CLHA gel effectively mitigated the initial burst release and provided a more sustained TA release profile over one month. <i>In vivo</i> evaluation in rabbits demonstrated that TA@PCL@CLHA significantly reduced the peak plasma concentration (<i>C_max</i> reduced by approximately 65%) and decreased systemic exposure (<i>AUC_0-∞</i> reduced by about 49%), while maintaining detectable drug levels in the synovial fluid for at least 30 days.</p><p><strong>Conclusion: </strong>The TA@PCL@CLHA microsphere-gel composite provides an effective local drug delivery system with minimized systemic exposure, offering a promising strategy for OA treatment.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"720-734"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149442","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":"Formulation of metered-dose inhalers containing beclomethasone dipropionate using quality by design approach.","authors":"Tu Man Tieu, Van-Hoa Huynh, Thai-Duong Nguyen, Dinh-Duy Pham","doi":"10.1080/03639045.2026.2635386","DOIUrl":"10.1080/03639045.2026.2635386","url":null,"abstract":"<p><strong>Objective: </strong>Metered-dose inhalers (MDIs) containing corticosteroids are widely prescribed for the treatment of asthma and chronic obstructive pulmonary disease, but the high cost of brand-name products limits access in developing countries. A quality by design (QbD) approach offers a systematic framework for developing cost-effective generic alternatives while ensuring consistent product quality.</p><p><strong>Significance: </strong>Our findings demonstrate that a QbD framework can accelerate formulation optimization, enhance product reliability, and support patient access to affordable, high-quality corticosteroid inhalers.</p><p><strong>Methods: </strong>Beclomethasone dipropionate (BDP) MDI formulation was developed and optimized using QbD principles, focusing on establishing critical quality attributes (CQAs) and defining the design space for key formulation parameters. CQAs were identified through risk assessment.</p><p><strong>Results: </strong>A mixture/I-optimal design was employed to optimize ethanol (5-15%), oleic acid (0.05-2%), and HFA-134a propellant (82.8-94.75%). Statistical modeling in Design-Expert (Stat-Ease Inc., Minneapolis, MN) defined the control space and an optimized formulation region for these components. Formulations within this space consistently met target specifications, including a mass median aerodynamic diameter (MMAD) of 3.26 ± 0.17 μm (target < 5 μm), fine particle fraction (FPF) of 60.4 ± 2% (target ≥ 55%), and delivered dose uniformity (DDU) of 99.7 ± 1.5% (target: 75-125%). The model showed high predictability, with <i>R</i>² values of 0.98, 0.88, and 0.93 for MMAD, FPF, and DDU, respectively.</p><p><strong>Conclusion: </strong>QbD approach enabled the development of a robust design space for a generic BDP MDI. The optimized formulation demonstrated comparable performance to the reference product, supporting the development of more affordable inhaled corticosteroid therapies.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"780-792"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147276086","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}