International Journal of Pharmaceutics: X最新文献

{"title":"Co-assembled Glycyrrhiza nanoparticles embedded supramolecular protein hydrogels to enhance licochalcone A release for acute inflammation management","authors":"Zhuxian Wang ,&nbsp;Jun Liu ,&nbsp;Yufan Wu ,&nbsp;Yamei Li ,&nbsp;Hongxia Zhu ,&nbsp;Qiang Liu ,&nbsp;Bin Yang","doi":"10.1016/j.ijpx.2025.100343","DOIUrl":"10.1016/j.ijpx.2025.100343","url":null,"abstract":"<div><div>Licochalcone A (LA) garnered remarkable acclaim in acute inflammation therapy, however, poor release capability from the matrix and oral bioavailability restrict its oral delivery. To address this challenge, licorice-derived glycyrrhizic acid (GA) and LA were co-assembled into GA-LA (GLA) binary co-assembled <em>Glycyrrhiza</em> nanoparticles (BCGNs), which were subsequently incorporated into supramolecular hydrogel matrix. GLA BCGNs demonstrated a remarkable capacity to scavenge various reactive oxygen species (ROS) and facilitated the cascade process of O₂^•−-H₂O₂-O₂ in vitro. Subsequently, GLA was dispersed in nano form into ovalbumin (OVA) and rhamnose (Rha) solutions, which were next self-assembled into OVA-Rha-GLA hydrogels. Remarkably, the introduction of Rha induced disordered secondary conformation of OVA, which decreased its mechanical properties and inherent binding energy, thereby shaping the three-dimensional supramolecular spatial structures of OVA-Rha-GLA networks. The assembly mechanisms indicated that the hydrogen bonding predominantly drove the assembly of loose supramolecular networks surrounded by -OH, -CH₂ and C<img>O bonds on the Rha and OVA. Notably, the conformational transformation facilitated faster LA release, confirmed by computational simulation analysis, which was conducive to acute inflammation curation. Therefore, OVA-Rha-GLA exhibited excellent anti-inflammation and ROS-scavenging versatilities, displaying improved oral bioavailability compared to hydrogels lacking BCGNs or Rha in cellular and animal acute inflammation experiments. The results provided novel BCGNs-embedded supramolecular hydrogel systems to improve the drug release and anti-inflammatory bioactivities of LA, which demonstrated great promise in the management of acute inflammation.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100343"},"PeriodicalIF":5.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144189951","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}

{"title":"Glycyrrhizic acid and its carrier-free micellar formulation: Unraveling the potential for enhanced oral prevention of hearing loss","authors":"Huaan Li ,&nbsp;Bohan Lin ,&nbsp;Shuangwu Wang ,&nbsp;Ying Zhang ,&nbsp;Zeming Zhou ,&nbsp;Dingsheng Wen ,&nbsp;Zhifeng Zhang ,&nbsp;Xiaohua Feng ,&nbsp;Lu Wen ,&nbsp;Jun He ,&nbsp;Gang Chen","doi":"10.1016/j.ijpx.2025.100340","DOIUrl":"10.1016/j.ijpx.2025.100340","url":null,"abstract":"<div><div>Hearing loss, a global health concern, significantly impacts patients with delayed language development, impaired neurocognitive function, and severe social problems. The main cause is the cochlear hair cell damage induced by oxidative stress and inflammation from ototoxic drugs, noise exposure or diabetes. Glycyrrhizic acid (GA), derived from edible herb licorice, is widely utilized in traditional Chinese medicine and clinical treatments for liver diseases. However, its potential in preventing hearing loss remains largely unexplored. Herein, we propose GA as a novel otoprotective agent and demonstrate its capability to prevent hearing loss. Our results show that GA effectively reduces oxidative stress and inflammation induced by cisplatin, aminoglycosides, or even noise and diabetes, thereby protecting cochlear hair cells. In hearing loss models, two commonly used administration methods were compared, with tympanic injection providing better protective effects than oral administration of GA. To enhance oral bioavailability, GA is employed as both the medicine and excipient, and formulated into micelles with curcumin, another extensively used bioactive compound. Interestingly, formulation parameters such as feeding ratio and temperature have little impact on micelle size but significantly affect the drug loading efficiency. The carrier-free strategy can achieve a high drug loading capacity and significantly increase the drug concentration in blood, offering improved preventive efficacy. Notably, the micelles also exhibit protection on kidneys and liver, and do not compromise the antitumor activity of cisplatin. Therefore, GA holds promise as an otoprotective candidate, with potential clinical applications for oral prophylaxis of hearing loss using the micellar formulation.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100340"},"PeriodicalIF":5.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144170464","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}

{"title":"A pragmatic mixing model for the evaluation of powder flow properties of multicomponent pharmaceutical blends","authors":"Daniel Yanes ,&nbsp;Rachael Shinebaum ,&nbsp;Georgios Papakostas ,&nbsp;Gavin K. Reynolds ,&nbsp;Sadie M.E. Swainson","doi":"10.1016/j.ijpx.2025.100339","DOIUrl":"10.1016/j.ijpx.2025.100339","url":null,"abstract":"<div><div>Maintaining flowability of pharmaceutical blends is critical for operational efficiency in state-of-the-art continuous direct compression (CDC) manufacturing, with poor flow potentially resulting in API loss, increased experimental work and increased time to market. Consequently, flowability is a crucial consideration in the design of formulations and must be considered throughout the development process when changes are introduced. Traditionally, understanding flow properties has required testing large amounts of material, particularly when evaluating formulation options. This has led to research into developing predictive flow models to reduce experimental burden. Current models with good predictive capacity, such as using granular bond number, require non-routine measurements such as mechanical surface energy. Three mixture designs, each using three pharmaceutical materials, were developed to investigate flow properties and allow the evaluation of a number of mixing models for predicting flowability with minimal experimental input requirements. The resultant models ranged in complexity from simple first order mixture models to more complex third order models with binary and ternary interaction parameters. An analysis of the experimental cost versus prediction accuracy suggested that while the more complex models delivered the most accurate predictions, a first order mass weighted model using inverse FFC was capable of providing good predictions in return for a more manageable experimental burden, with an R² value of 0.68, root mean square error of 2.88 and a mean absolute percentage error of 0.21. This model has the potential to provide valuable insights during early formulation design and development where material is scarce and good flowability is crucial.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100339"},"PeriodicalIF":5.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124987","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}

{"title":"Selective laser sintering of distinct drug and polymer layers as a novel manufacturing strategy for individually dosed tablets","authors":"Jonas Autenrieth ,&nbsp;Daniel Hedbom ,&nbsp;Maria Strømme ,&nbsp;Thomas Kipping ,&nbsp;Jonas Lindh ,&nbsp;Julian Quodbach","doi":"10.1016/j.ijpx.2025.100338","DOIUrl":"10.1016/j.ijpx.2025.100338","url":null,"abstract":"<div><div>Selective Laser Sintering (SLS) is an emerging additive manufacturing technology with potential for the production of personalized pharmaceuticals. In this study, we investigated a novel simplified formulation approach in SLS-based manufacturing of individually dosed, multi-layered tablets with distinct layers of pure active pharmaceutical ingredient (API) and excipient. Indomethacin (IND) was chosen as the model API, and polyvinyl alcohol (PVA) served as the excipient. Unlike conventional methods requiring powder blending, this approach utilizes separate powder tanks for IND and PVA, enabling direct printing of alternating layers in a single-step procedure.</div><div>We successfully fabricated tablets with controlled IND doses by varying the number of IND layers, maintaining consistent printing parameters across different compositions and confirming the API's chemical stability in the product. Since SLS is conventionally used for thermoplastic substances, the successful sintering of pure IND layers was a key achievement in the study, as this crystalline API is typically not printable separately. Energy dispersive X-ray spectroscopy (EDS) demonstrated the successful formation of distinct API and excipient layers. Differential scanning calorimetry (DSC) characterization revealed that the sintering process partially amorphized IND, which may enhance dissolution and bioavailability. Dissolution testing indicated that the printed tablets exhibited improved dissolution rates compared to raw IND powder.</div><div>The study successfully demonstrated the possibility of SLS-based production for personalized dosing by omitting powder blending steps. The ability to create individualized dosages with minimal excipients and simplified processing represents a step toward further investigation of SLS for clinical settings, including hospital and pharmacy-based drug production.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100338"},"PeriodicalIF":5.2,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144115913","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}

{"title":"Alleviating ulcerative colitis via rectal administration: Enhancing the therapeutic effects of silk sericin-proanthocyanidins nanoparticles with a Poloxamer thermosensitive in situ gel","authors":"Jie Zhang ,&nbsp;Chunru Wang ,&nbsp;Xiaochen Wu ,&nbsp;Yu Lin","doi":"10.1016/j.ijpx.2025.100337","DOIUrl":"10.1016/j.ijpx.2025.100337","url":null,"abstract":"<div><div>Ulcerative colitis, a type of inflammatory bowel disease, primarily impacts the colon's mucous membrane, leading to distressing symptoms. Both healthcare and socioeconomic aspects are significantly impacted by this condition. In this study, we stabilized proanthocyanidins (PAC) with silk sericin (SS) to create SS/PAC nanoparticles. These nanoparticles were then loaded into a thermosensitive in situ hydrogel made with Poloxamer. The effectiveness and safety of the resulting SS/PAC/P thermosensitive hydrogel were evaluated using a dextran sulfate sodium (DSS)-induced model of ulcerative colitis, through rectal administration of the hydrogel. SS/PAC/P demonstrated excellent compatibility and hemocompatibility. It exhibited strong antioxidant and anti-inflammatory properties, effectively relieving ulcerative colitis by counteracting its adverse effects. It alleviated abnormal disease activity index (DAI) scores, improved colon conditions, enhanced histological characteristics, and regulated microbial homeostasis. The superior effectiveness of SS/PAC/P hydrogel in vivo can be attributed to its prolonged residence time at the targeted site of administration, facilitating the continuous release of SS/PAC from the hydrogel. SS/PAC/P has shown potential as a promising therapeutic intervention for managing ulcerative colitis.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100337"},"PeriodicalIF":5.2,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144106069","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}

{"title":"Formulation, in silico, in vitro characterization, cytotoxicity and cellular uptake of cyclodextrin complexes and ion pairing/salt formation with functional excipients (azelaic acid, tartaric acid, and arginine) with raloxifene","authors":"Hamdy Abdelkader ,&nbsp;Adel Al-Fatease ,&nbsp;Ali H. Alamri ,&nbsp;Mai E. Shoman ,&nbsp;Hend Mohamed Abdel-Bar ,&nbsp;Zeinab Fathalla","doi":"10.1016/j.ijpx.2025.100336","DOIUrl":"10.1016/j.ijpx.2025.100336","url":null,"abstract":"<div><div>With advancements in drug repurposing, the search for effective and less harmful anticancer agents remains a critical endeavor. Raloxifene, although not a typical anticancer drug, holds promise in this context. However, its poor solubility poses a significant challenge to its therapeutic potential and formulation efficiency. Functional excipients such as cyclodextrins (e.g., β-cyclodextrin, hydroxy propyl β-cyclodextrin, and Captisol) and pH-modifying excipients (e.g., tartaric acid, azelaic acid, and arginine) were investigated to enhance solubility, dissolution, cytotoxicity and cellular uptakes employing Caco-2 cell lines through binary solid dispersions. In silico studies suggested the potential for salt formation with raloxifene-azelaic acid and raloxifene-tartaric acid, as well as inclusion complexes with cyclodextrins. Experimental results showed that pH-modifying excipients, particularly tartaric and azelaic acids, significantly improved solubility (up to an 800-fold increase), outperforming cyclodextrins (8-fold increase) compared to the untreated drug. Cytotoxicity studies on the human breast cancer (Michigan cancer foundation, MCF-7) cells revealed that raloxifene-tartaric acid significantly enhanced cell killing, achieving efficacy comparable to the standard anticancer drug Taxol. Additionally, both fluorescence-labeled raloxifene: hydroxy propyl β-cyclodextrin coprecipitated mixtures (Coppt) and raloxifene: tartaric acid Coppt exhibited concentration- and time-dependent cellular uptake, with mean fluorescence intensity increasing significantly at 24 h, indicating rapid internalization and sustained intracellular retention, especially at higher concentrations. More interestingly, the superior cellular uptake was in favor of the latter, indicating the pH-modifying excipient tartaric acid, and these findings correlated well with solubility and dissolution studies.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100336"},"PeriodicalIF":5.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936980","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}

{"title":"An aptamer-conjugated mesoporous polydopamine formulation for synergistic targeted and photothermal therapy of hepatocellular carcinoma","authors":"Yue Yang ,&nbsp;Chonggao Wang ,&nbsp;Shiwei Liu ,&nbsp;Yewei Zhang","doi":"10.1016/j.ijpx.2025.100335","DOIUrl":"10.1016/j.ijpx.2025.100335","url":null,"abstract":"<div><div>This study aimed to create multifunctional nanoparticles (NPs), specifically [email protected] (AMLC), for the purpose of developing effective strategies for treating hepatocellular carcinoma (HCC) through targeted therapy and photothermal therapy (PTT). The study involved synthesizing mesoporous polydopamine (MPDA)-NPs, loading lenvatinib (Len) and Cy5.5 via incubation, and modifying AS1411 aptamer onto MPDA via a covalent chemical reaction. The NPs were characterized using techniques such as ultra-micro spectrophotometry, Fourier transform infrared spectroscopy, and transmission electron microscopy. Target-specific uptake and cell-killing assays were utilized to evaluate AMLC-mediated synergistic therapy while using Western blotting and immunofluorescence to confirm the underlying mechanism. Consequently, the nanoparticles (NPs) were successfully synthesized, demonstrating excellent solvent solubility and stability, with controlled drug release achieved in acidic environments (maximum release efficiency≈80 %). In vitro and in vivo studies revealed that these NPs could more effectively target hepatocellular carcinoma (HCC) cells, enhancing the targeting capability of lenvatinib. Under near-infrared (NIR) laser irradiation, the targeted photothermal therapy (PTT) exhibited significantly improved anticancer efficacy, with AMCL+PTT treatment resulting in up to 76 % tumor volume reduction‌ (<em>P</em> &lt; 0.01). The study demonstrates that AMLC, a multifunctional nano-delivery system, significantly enhances Lenvatinib's tumor-targeting capacity while exhibiting excellent biocompatibility. Combined with photothermal therapy (PTT), it demonstrates potent antitumor efficacy, showing promising clinical translation potential for hepatocellular carcinoma (HCC) therapy.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100335"},"PeriodicalIF":5.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882805","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}

{"title":"Ultra-sensitive pH responsive hydrogels with injectable and self-healing performance for controlled drug delivery","authors":"Yang Yu ,&nbsp;Yili Zhao ,&nbsp;Yujiao Zou ,&nbsp;Chanyi Lu ,&nbsp;Ni Li ,&nbsp;Zhiyuan Shi ,&nbsp;Xin Li ,&nbsp;Xixi Lai","doi":"10.1016/j.ijpx.2025.100334","DOIUrl":"10.1016/j.ijpx.2025.100334","url":null,"abstract":"<div><div>Ultra-sensitive pH-responsive drug delivery system designed to operate within the slightly acidic microenvironment of tumors are highly desired for hydrogel applications in cancer therapy. In this study, 4-Formylbenzoic acid modified polyvinyl alcohol (PVA-FBA, PF) was synthesized and utilized as a carrier for encapsulating the anticancer drug Doxorubicin (Dox). This was subsequently crosslinked with polyethylenimine (PEI) via benzoic-imine bond to form drug-loaded PVA-FBA/PEI hydrogel (D-PFP). The D-PFP hydrogel was characterized using various techniques. The results indicated that the optimal conditions for hydrogel preparation involved using PF-0.25 polymer, which had an aldehyde group content of 0.82 mmol/g, as the precursor, along with a 12 wt% precursor solution for crosslinking with a 5 wt% PEI solution. The resulting hydrogel exhibited good structural stability and favorable morphology. Drug release studies indicated that the hydrogel demonstrated minimal drug leakage under physiological conditions (pH 7.4), while exhibiting a significantly higher drug release rate at pH 6.8, thereby underscoring its superior pH sensitivity. Rheological evaluations further confirmed its injectability and self-healing properties. Moreover, the hydrogel displayed excellent cytocompatibility and significantly inhibited cancer cell activity at pH 6.8. These characteristics suggest the potential of this hydrogel as a drug delivery system with ultra-sensitive drug release properties, particularly for future applications in chemotherapy for cancer.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100334"},"PeriodicalIF":5.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838130","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}

{"title":"Does tablet shape and height influence survival of fluidized bed-granulated living microorganisms during compaction?","authors":"Karl Vorländer ,&nbsp;Lukas Bahlmann ,&nbsp;Arno Kwade ,&nbsp;Jan Henrik Finke ,&nbsp;Ingo Kampen","doi":"10.1016/j.ijpx.2025.100332","DOIUrl":"10.1016/j.ijpx.2025.100332","url":null,"abstract":"<div><div>The provision of effective probiotic formulations requires gentle processing to maintain the viability of the probiotic microorganisms, which is essential for their health-promoting effects. The drying of microorganisms by fluidized bed spray granulation and subsequent processing of the granules into tablets has proven to be a promising process route in previous studies of the same authors. In these, the influence of various factors was considered using cylindrical tablets with a diameter of 11.28 mm and a mass of 450 mg. These flat tablets are unpleasant to ingest and other tablet geometries should be considered for administration of probiotics but to date, no studies exist on the influence of geometric factors of the tableting tool and of the tablets on the survival of microorganisms. To address this aspect, the survival of <em>Saccharomyces cerevisiae</em> during the production of flat, round tablets with different tablet masses and thus heights as well as differently shaped convex tablets is determined and related to the physical-mechanical tablet properties to derive process-structure-property relationships. It turned out that higher tablet heights were advantageous regarding microbial survival and mechanical strength which is attributed to a lower elastic recovery. However, the use of differently shaped tools had a smaller influence on microbiological and mechanical tablet properties since the global tablet porosity was hardly affected.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100332"},"PeriodicalIF":5.2,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143799764","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}

{"title":"An iterative process and mixture design approach for dry granulated ternary blends of filler-binders","authors":"Niclas Märkle ,&nbsp;Gernot Warnke ,&nbsp;Miriam Pein-Hackelbusch","doi":"10.1016/j.ijpx.2025.100331","DOIUrl":"10.1016/j.ijpx.2025.100331","url":null,"abstract":"<div><div>Roller compaction/dry granulation (RC/DG) is a key process in pharmaceutical manufacturing for improving powder flowability, density, and segregation resistance. Advanced statistical modeling was used to optimize RC/DG process parameters and subsequently binder compositions by employing process and mixture design experiments. The authors used microcrystalline cellulose (MCC), silicified MCC (SMCC), and dicalcium phosphate (DCP) as filler-binder examples in RC/DG experiments. Granule and tablet properties, including flowability, bulk and tapped densities, as well as resistance to crushing, were analyzed using compendial methods. The process design experiments confirmed that RC/DG reduces manufacturability compared to direct compression. Optimal processing conditions, balancing sufficient tablet strengths and granule formation, were identified to be between 20 (SCF * ϑ) [kN/cm] and ∼ 60 (SCF * ϑ) [kN/cm]. Thereby (ϑ) is defined as the screw-to-roll speed ratio and (SFC) as the specific compaction force. Mixture design experiments revealed optimal mixtures balancing SMCC, MCC, and DCP to achieve desired properties like low angle of repose, high bulk density, and strong tablets. These findings provide guidance for selecting formulations and process parameters in RC/DG applications. The derived ‘SCF * ϑ’- factor was found to effectively describe the granulation intensity. A superimposed mixture design model based on precise target values of the parameters bulk density, flow properties, and breaking force allowed identification of the best formulation.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100331"},"PeriodicalIF":5.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776954","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}