Drug Development and Industrial Pharmacy最新文献

{"title":"Chemical aspects of controlled cisplatin release and apoptosis via <i>Nerium oleander</i> latex nano-carriers in breast cancer cells.","authors":"Sultan Saad Almadhhi, Raju Suresh Kumar, D V Surya Prakash, Nipun Babu Varukattu, Chandrababu Rejeeth","doi":"10.1080/03639045.2026.2711865","DOIUrl":"10.1080/03639045.2026.2711865","url":null,"abstract":"<p><p>Plant-derived nano-carriers offer a sustainable and targeted strategy for cancer therapy. This study reports the synthesis and characterization of a latex-hybrid nano-carrier derived from <i>Nerium oleander</i> (LHNC), engineered for cisplatin (CDDP) delivery in breast cancer models. Physicochemical analyses confirmed stable, porous nanostructures with uniform particle size (∼120-150 nm), moderate surface charge (+21 mV), and high drug loading efficiency (∼85%). The system exhibited pH-responsive sustained release under acidic conditions, mimicking the tumor microenvironment. Biological evaluations demonstrated that LHNC/CDDP significantly enhanced cytotoxicity compared to free CDDP, reducing MCF-7 cell viability to ∼38% at 24 hr. Mechanistic studies revealed elevated ROS generation, mitochondrial membrane depolarization, nuclear condensation, and caspase-mediated apoptosis. Flow cytometry confirmed pronounced G2/M arrest and increased apoptotic fractions, validating the pro-apoptotic and anti-proliferative effects of the nano-carrier. Comparative analyses across luminal (MCF-7), triple-negative (MDA-MB-231), and non-tumorigenic (MCF-10A) models highlighted selective cytotoxicity toward malignant cells while sparing normal epithelial cells. Collectively, these findings position LHNC/CDDP as a promising bioinspired nanocarrier platform that integrates natural polymer advantages with chemotherapeutic precision. While the <i>in vitro</i> data provide compelling proof-of-concept, translational application requires rigorous toxicological evaluation, dose optimization, and <i>in vivo</i> validation, particularly given the bioactive cardiac glycosides in <i>N. oleander.</i></p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"2031-2048"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618828","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":"Evaluation of compatibility of domperidone with selected excipients used in preparation of orally disintegrating tablets.","authors":"Hamad S Alyami, Amjad Khan, Shabnam Nazir, Majeed Ullah, Abdul Wahab, Mohammad Naseer Abbas, Fahim Ullah Khan, Muhammad Asghar Khan","doi":"10.1080/03639045.2026.2714990","DOIUrl":"10.1080/03639045.2026.2714990","url":null,"abstract":"<p><strong>Objective: </strong>This study aims systematic evaluation of potential drug excipient interactions and by using a multi technique analytical approach.</p><p><strong>Significance: </strong>This study will help in finding out compatibility among domperidone and different excipients, and will facilitate excipients selection for development a stable formulation of ODTs.</p><p><strong>Methods: </strong>Binary mixtures of domperidone and excipients which are commonly used in preparation of solid dosage forms were prepared (1:1 w/w), with and without added moisture. Studied excipients included microcrystalline cellulose, Tablettose-80 (spray-dried lactose), croscarmellose sodium, magnesium stearate, and aspartame. Samples were subjected to higher temperature and relative humidity (45 °C and 75% RH) for 90 days, as per ICH guidelines. Samples were analyzed at regular interval for drug content (by high-performance liquid chromatography), chemical interaction (by Fourier transform infrared [FTIR] spectroscopy), solid state characterization (by differential scanning calorimetry and powder X-ray diffraction [XRD]), and moisture uptake (by Karl Fischer titration).</p><p><strong>Results: </strong>Drug content of all the samples remained within the range of 95%-105% throughout the study. FTIR spectra showed absence of chemical interactions as all the functional groups remained unchanged. Characteristic melting endotherm was observed in DSC thermograms. XRD analysis showed same crystallinity and polymorphic transitions were not observed. Depending upon their physicochemical properties, excipient showed different levels of hygroscopicity. Highest water sorption was observed with croscarmellose sodium and lactose whereas magnesium stearate remained non hygroscopic. Moisture uptake study showed that chemical or solid-state stability of domperidone was not affected by exposure to high relative humidity.</p><p><strong>Conclusions: </strong>Domperidone exhibited robust chemical and physical stability across all excipient environments tested. While excipient hygroscopicity varied significantly, no incompatibilities were detected that would limit formulation development of ODTs.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"2065-2077"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148677463","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":"A review of emerging drug delivery strategies to protect cannabidiol from chemical degradation.","authors":"Giovana Carolina Bazzo, Hellen Karine Stulzer","doi":"10.1080/03639045.2026.2707223","DOIUrl":"10.1080/03639045.2026.2707223","url":null,"abstract":"<p><strong>Objective: </strong>This review provides an overview of recent advances in cannabidiol (CBD) delivery systems aimed at improving its chemical stability. Emphasis is placed on the relationship between formulation type, storage conditions, and the resulting chemical stability of CBD, with the aim of supporting the development of novel cannabinoid-based pharmaceuticals.</p><p><strong>Significance: </strong>CBD has attracted increasing interest due to its diverse pharmacological activities and lack of psychoactive effects. Despite its therapeutic potential, the development of new CBD-based drug delivery systems remains a significant challenge. CBD is chemically unstable and can degrade when exposed to heat, light, oxygen, certain solvents or extreme pH conditions, potentially reducing its efficacy and forming psychoactive degradation products.</p><p><strong>Key findings: </strong>Solid CBD formulations offer advantages due to their greater stability compared with liquid forms. However, CBD's poor water solubility and intrinsic instability present major formulation challenges. Amorphous solid dispersions, cyclodextrins, microparticles, and nanostructured systems have been explored to overcome these limitations. Liquid delivery systems, including emulsions and nanoemulsions, can also enhance stability by incorporating CBD into the oil phase, with oil selection and antioxidants playing key roles in minimizing degradation. Among these approaches, nanostructured lipid carriers have shown particular promise in preserving CBD stability.</p><p><strong>Conclusions: </strong>The appropriate selection of CBD delivery systems is essential to ensure its chemical stability and to support the development of effective cannabinoid-based pharmaceuticals. Understanding the interplay between formulation design and storage conditions is crucial for optimizing CBD stability, extending shelf life, and ensuring the safety and efficacy of future CBD-containing therapeutic products.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"1893-1911"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548121","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":"Comparative evaluation of nanofiber and wafer-based systems for ophthalmic delivery of a water-soluble drug.","authors":"Fatemeh Tavakoli, Mahya Farazmand, Marzieh Akrami, Mahsa Golmohammadi, Milad Imeni, Mahdiyeh Khajehkhalili, Ali Mohammad Ranjbar, Vahid Ramezani","doi":"10.1080/03639045.2026.2710362","DOIUrl":"10.1080/03639045.2026.2710362","url":null,"abstract":"<p><strong>Objective: </strong>Aimed at developing and comparing wafer and nanofibers as biocompatible and prolong release ophthalmic delivery systems, we have prepared various formulations of sulfacetamide-a soluble drug- and evaluate them.</p><p><strong>Methodology: </strong>Wafers were prepared using the casting and freeze-drying method, while nanofibers were fabricated <i>via</i> an electrospinning system. Various formulations containing polyvinyl alcohol (PVA) and sodium alginate (SA) were employed, with SA ratios ranging from 0 to 15%. Morphological characterization with SEM microscopy, thermal behavior, <i>in vitro</i> drug release, bio-adhesive strange, antibacterial activity and fibroblast cell cytotoxicity of various formulations of nanofiber and wafer were evaluated. Additionally, glutaraldehyde was used for cross-linking the formulations.</p><p><strong>Results: </strong>Wafers exhibited a porous structure with nanosized walls. In addition, various formulations of nanofibers were prepared with nano-sized thicknesses ranging from 420.55 to 153.42 nm. Wafers showed a slow-release profile lasting more than six hours, similar to that of nanofibers in most cases with kinetic of Higuchi order. Cross-linking both systems further sustained drug release for more than 7 h, particularly in formulations with higher sodium alginate content. The nanofiber exhibited higher antibacterial activity against <i>Escherichia coli</i> and <i>Staphylococcus aureus</i>, particularly when formulated 10% of SA. Additionally, nanofibers showed higher cell viability upon contact with fibroblast cells and higher bioadhesive strength ranging from 2.3 to 3.6 N/cm² in compare with wafers (ranging from 1.6 to 2.5 N/cm²).</p><p><strong>Conclusion: </strong>Formulations of pharmaceutical wafers and nanofibers are interchangeable, and are suitable for prolonged delivery of sulfacetamide, a water-soluble drug; however, nanofibers showed higher biocompatibility, antibacterial activity and bioadhessiveness.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"1987-2000"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148600239","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":"Multi-compartment pharmacokinetics and tissue bioavailability of Coenzyme Q10 from a phospholipid-based self-nanoemulsifying drug delivery system in rats: a distribution pattern consistent with a possible lymphatic contribution.","authors":"Krishnamurthy Narasimha Prasad, Chaithra Chandrashekar, Srinivasa Krishnappa, Girish Gannareddy Vasantha, Shamprasad Phadnis, Manu Kaggere Narasimhamurthy","doi":"10.1080/03639045.2026.2708958","DOIUrl":"10.1080/03639045.2026.2708958","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate a proprietary phospholipid-based self-nanoemulsifying CoQ10 delivery system using an integrated multi-compartment framework encompassing plasma pharmacokinetics, erythrocyte uptake, tissue distribution, and distribution-based indicators consistent with a possible contribution of intestinal lymphatic transport.</p><p><strong>Significance: </strong>Current CoQ10 SNEDDS studies primarily assess plasma bioavailability, with limited evidence regarding intracellular delivery, tissue distribution, or absorption pathway modulation. This study extends evaluation beyond plasma-only metrics toward mechanistic, distribution-informed pharmacokinetics.</p><p><strong>Methods: </strong>The formulation was characterized for droplet size, zeta potential, and drug loading after aqueous reconstitution. Cellular metabolic activity was assessed in Caco-2 cells using the MTT assay. <i>In vivo</i> pharmacokinetic and tissue-distribution studies were performed in Sprague-Dawley rats administered a single oral dose of crystalline CoQ10 or the phospholipid-based SNEDDS (30 mg/kg; <i>n</i> = 3/group) in this exploratory, hypothesis-generating study. Plasma, erythrocyte, and tissue CoQ10 concentrations were quantified by HPLC.</p><p><strong>Results: </strong>The SNEDDS formed a stable nanoemulsion (104.2 ± 2 nm; PDI 0.221; zeta potential -52.1 mV). In Caco-2 cells, the formulation enhanced mitochondrial metabolic activity in a concentration-dependent manner. <i>In vivo</i>, the SNEDDS increased plasma Cmax 2.7-fold and AUC_0-24 h 1.5-fold versus crystalline CoQ10 (relative bioavailability 149%). Erythrocyte CoQ10 concentrations and tissue deposition increased across all organs examined (1.3-4.5-fold). The liver-to-intestine concentration ratio inverted from 1.51 to 1.02, consistent with a possible contribution of intestinal lymphatic transport. Disproportionate Cmax enhancement relative to AUC indicated rate-limited absorption bypass.</p><p><strong>Conclusion: </strong>The formulation enhanced systemic, cellular, and tissue-level CoQ10 delivery, supporting mechanistic evaluation beyond plasma bioavailability alone. The observed tissue distribution pattern is consistent with a potential contribution of intestinal lymphatic transport, although direct confirmation requires dedicated lymphatic transport studies.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"1948-1965"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148677534","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":"Safety, tolerability, and pharmacokinetics of oral FM888 in healthy Chinese adults: a Phase I, randomized, double-blind, placebo-controlled study.","authors":"Yan Jiang, Fang Tian, Jianren Zhou, Yuanyuan Li, Wei Wang, Hua Xu, Linyan Gao, Hengyan Qu","doi":"10.1080/03639045.2026.2710803","DOIUrl":"10.1080/03639045.2026.2710803","url":null,"abstract":"<p><strong>Purpose: </strong>Targeting adenylate cyclase 1 (AC1) offers a novel, non-opioid strategy for pain treatment. The active moiety of FM888 had been evaluated previously in an older tablet formulation. Phase I study assessed the safety, tolerability, pharmacokinetics, and metabolite profile of a new capsule formulation in healthy Chinese volunteers, with single doses escalated to 1200 mg and multiple doses to 600 mg Q12h-three times the previous maximum-to support Phase II dose selection.</p><p><strong>Methods: </strong>In this single-center, randomized, double-blind, placebo-controlled trial, 86 healthy Chinese adults received single (100-1200 mg; <i>n</i> = 50) or multiple ascending doses (200-600 mg Q12h for 7 days; <i>n</i> = 36). Safety, tolerability, pharmacokinetics, and metabolite profiling were assessed.</p><p><strong>Results: </strong>FM888 was well tolerated across all doses. The maximum tolerated dose was 1200 mg (single) and 600 mg Q12h (multiple). All adverse events were mild, with no serious events, discontinuations, or dose‑limiting toxicities. Pharmacokinetics were dose‑proportional over 100-1200 mg. Mean terminal half‑life was 12.66-36.49 h, steady state was reached by Day 5 with minimal accumulation (<i>R_{ac, AUC}</i>: 1.34-1.68), and renal excretion of unchanged drug was low (<1.52%). Six major metabolites were identified, formed mainly <i>via</i> hydroxylation, oxidation, and N‑dealkylation.</p><p><strong>Conclusion: </strong>FM888 demonstrated a favorable safety profile and predictable pharmacokinetics in healthy subjects. These results support the continued clinical development of FM888 and progression to Phase II trials for chronic pain.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"2015-2030"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148600289","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":"Linoleic acid-based pH-sensitive 5-ASA nanocubosome pellets for colon targeting in ulcerative colitis: <i>in vitro</i> and <i>in vivo</i> comparison with non-pH-sensitive and conventional formulations.","authors":"Ali Asghar Khakshur, Abbas Akhgari, Hosseinzadeh Zahra, Hossein Kamali, Kofi Asare-Addo, Ali Nokhodchi","doi":"10.1080/03639045.2026.2708900","DOIUrl":"10.1080/03639045.2026.2708900","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to design and evaluate pH-sensitive pellets loaded with 5-aminosalicylic acid (5-ASA) for targeted colon delivery in ulcerative colitis (UC) therapy.</p><p><strong>Significance: </strong>The proposed formulation leverages glyceryl monooleate (GMO) and linoleic acid (LA) as liquid crystal precursors to achieve site-specific drug release.</p><p><strong>Methods: </strong>Liquid crystal nanoparticles (LCNPs) were prepared from a GMO bulk phase using a top-down method, with LA added for pH sensitivity. The formulations were then evaluated for drug loading, encapsulation efficiency, and structure by polarized light microscopy, with drug release tested at pH 1.2 and 6.8. The LCNPs dispersions were then used to make pellets using the extrusion-spheronisation technique. Drug-excipient interactions were examined by FTIR and DSC. The pellet formulations were finally tested in a rat ulcerative colitis (UC) model by comparing colon damage scores across treatment groups.</p><p><strong>Results: </strong>The pH-sensitive pellets containing LCNPs exhibited a uniform morphology, desirable aspect ratio, and sufficient mechanical strength. The <i>in vitro</i> release profile demonstrated a 5.7-fold higher drug release at pH 6.8 compared to pH 1.2. This targeted release was ascribed to a pH-triggered phase transition of the LA and electrostatic repulsion between the ionized drug and the carrier. The <i>in vivo</i> results confirmed that the pH-sensitive pellets elicited the most pronounced and statistically significant (<i>p</i> < 0.05) reduction in colon damage scores.</p><p><strong>Conclusion: </strong>The developed pellet system, which encapsulates 5-ASA within GMO/LA-based liquid crystal nanoparticles, presents a highly promising platform for targeted drug delivery in the treatment of ulcerative colitis.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"1929-1947"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148721794","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 evaluation of rizatriptan benzoate orally disintegrating tablets for migraine treatment.","authors":"Nevin Çelebi, Emine Tuncay","doi":"10.1080/03639045.2026.2713612","DOIUrl":"10.1080/03639045.2026.2713612","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to develop rizatriptan (RZT) benzoate orally disintegrating tablets (ODTs), used in migraine treatment, using various excipients and, in particular, super-disintegrants, through the direct compression method, and to compare them with a commercial product (Maxalt^® RPD).</p><p><strong>Significance: </strong>Migraine is a common disease that affects quality of life. ODTs are the preferred dosage form due to their rapid effect and patient compliance. In this study, ODTs with rapid disintegration time, rapid release, and high porosity were developed using superdisintegrant for RZT.</p><p><strong>Methods: </strong>ODT formulations were prepared by direct compression method using superdisintegrants such as Ludiflash^®, Ludipress^®, and Pharmaburst^™ along with other excipients. Disintegration time and <i>in vitro</i> dissolution tests were performed and compared with Maxalt^® RPD. Furthermore, the porosity, water absorption rate, wetting time, and surface morphology of the tablets were also examined. The interactions between RZT and excipients were investigated using DSC and XRD studies.</p><p><strong>Results: </strong>ODT formulations containing Ludiflash^® and Pharmaburst™ were found to be the most suitable according to their disintegration time, dissolution profiles. It was observed from the dissolution profile of the commercial product that 100% of the drug was dissolved within 3 min. This is thought to be due to Maxalt^® RPD being manufactured by lyophilization. A highly porous structure was clearly observed on the surface of ODTs. There was no interaction between RZT and excipients.</p><p><strong>Conclusion: </strong>As a result, ODT formulation of RZT, used in the treatment of migraine, has been successfully developed.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"2049-2064"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663656","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 of an injectable thermosensitive chitosan-based hydrogel for localized rutin delivery optimized using Box-Behnken design.","authors":"Suman Khurana, Parveen Kumar Goyal, Shrestha Sharma, Syed Arman Rabbani","doi":"10.1080/03639045.2026.2717215","DOIUrl":"10.1080/03639045.2026.2717215","url":null,"abstract":"<p><strong>Objective: </strong>The objective of the present study was to develop, optimize, and evaluate a chitosan (CS)-based hydrogel incorporating rutin for localized drug-delivery.</p><p><strong>Significance: </strong>Rutin, a naturally occurring flavonoid, possesses significant antioxidant, anti-inflammatory, and anticancer properties. However, its therapeutic applications are limited due to poor solubility and low bioavailability. The development of a CS-based injectable hydrogel system offers a promising strategy for enhancing localized delivery, improving drug retention, and achieving release at the target site.</p><p><strong>Methods: </strong>Box-Behnken Design (BBD) was employed for optimization, where CS concentration (A) and β-Gly concentration (B) were selected as critical material attributes (CMAs), and stirring speed (C) was selected as a critical process parameter (CPP). The hydrogel formulations were evaluated based on parameters including gelation time and swelling ratio. Additionally, rheological properties and <i>in vitro</i> drug-release studies were performed to assess formulation performance.</p><p><strong>Results: </strong>BBD identified an optimized formulation comprising 1.8% w/v CS, 35% w/v β-Gly, and a stirring speed of 460 rpm, which produced a hydrogel with a gelation time of 148 ± 1.1 s and a swelling ratio of 134.45% ± 1.4%. The experimental responses showed close agreement with the predicted values, confirming the robustness of the optimization model. The optimized hydrogel exhibited shear-thinning behavior suitable for injection and achieved approximately 86% cumulative rutin release over 24 h. Drug-release followed the Korsmeyer-Peppas model, indicating a combined diffusion and polymer relaxation mechanism.</p><p><strong>Conclusions: </strong>The QbD-based BBD approach enabled the efficient optimization of an injectable thermosensitive CS-based hydrogel system for localized delivery of rutin. The formulation exhibited desirable physicochemical and rheological properties along with controlled drug-release behavior. This hydrogel system represents a promising approach for enhancing the therapeutic efficacy of rutin in localized treatment applications.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"2091-2105"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711755","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 of discriminatory and biopredictive bicarbonate buffer-based dissolution method to screen delayed release formulations.","authors":"Juilee Kulkarni, Bibhuranjan Panigrahi, Usha Nayak, Sajeev Chandran","doi":"10.1080/03639045.2026.2717211","DOIUrl":"10.1080/03639045.2026.2717211","url":null,"abstract":"<p><strong>Objective: </strong>To develop a novel, discriminatory and biopredictive bicarbonate buffer (BB)-based dissolution method to understand the behavior of oral delayed release (DR) formulations containing Mesalamine.</p><p><strong>Significance: </strong>Conventional dissolutions have limitations in obtaining discrimination and predictive <i>in vivo</i> behavior for various DR formulations, as it does not mimic the physiological buffering. For DR formulations, functional coat opening time plays a crucial role in determining the initial drug release. BB is a dynamic system and has natural ability to gradually increase the pH due to evaporation of CO₂. This was considered as an advantage to discriminate pH sensitive DR coatings.</p><p><strong>Methods: </strong>USP-III BB dissolution condition with 10 DPM agitation was developed. Design of experiments (DoE) approach was used to study the impact of agitation and bicarbonate molarity on rate of pH change of BB. A relation of <i>in vitro</i> onset of release with <i>in vivo</i> onset of drug absorption and C_max was established to predict the <i>in vivo</i> formulation behavior.</p><p><strong>Results: </strong>Developed dissolution showed differences in onset of drug release for all formulations. DoE showed that agitation had significant impact on rate of pH change of BB irrespective of molarity. A strong linear correlation was obtained for <i>in vitro</i> drug release onset with <i>in vivo</i> onset of drug absorption and C_max (R² >0.99) at 10 DPM agitation. The % prediction error of <10 for <i>in vivo</i> onset of release and <4 for C_max was observed.</p><p><strong>Conclusions: </strong>This work demonstrates that dissolution in BB is more discriminatory and biopredictive than conventional dissolutions in predicting the onset of release and C_max for Mesalamine DR formulations.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"2078-2090"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789359","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}