Pharmaceutics最新文献

{"title":"Selective Inhibition of <i>Yersinia enterocolitica</i> Type III Secretion by <i>Lindera obtusiloba</i> Extract and Cinnamtannin B1.","authors":"Jin-Hee Yoo, Tae-Jong Kim","doi":"10.3390/pharmaceutics17091217","DOIUrl":"10.3390/pharmaceutics17091217","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Selective inhibition of bacterial virulence factors is a promising strategy to convert pathogenic bacteria into non-pathogenic commensals, circumventing the challenge of antibiotic resistance. This approach enables the host immune system to eliminate virulence-attenuated pathogens. <b>Methods</b>: In this study, we evaluated the effects of <i>Lindera obtusiloba</i> Blume extract and cinnamtannin B1, the active component of the ethyl acetate fraction, on the type III secretion system (T3SS) of <i>Yersinia enterocolitica</i>. <b>Results</b>: The ethyl acetate fraction, at 100 mg/L, effectively suppressed all three T3SS components-the flagellar, Ysa, and Ysc T3SSs. Cinnamtannin B1, isolated from the ethyl acetate fraction through separation and identified through nuclear magnetic resonance spectrometer analysis, significantly inhibited flagellar and Ysa T3SS secretion, while selectively inhibiting expression of key effector proteins YopH and YopO in the Ysc T3SS. Additionally, cinnamtannin B1 reduced <i>Y. enterocolitica</i>-induced RAW 264.7 macrophage mortality and prevented poly (ADP-ribose) polymerase degradation, a marker of apoptosis. <b>Conclusions</b>: These findings suggest cinnamtannin B1 from <i>L. obtusiloba</i> as a selective T3SS-targeting compound with mechanistic potential for anti-virulence intervention. Further in vivo validation will be necessary to evaluate its therapeutic applicability.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formulation Studies on Microemulsion-Based Polymer Gels Loaded with Voriconazole for the Treatment of Skin Mycoses.","authors":"Michał Gackowski, Anna Froelich, Oliwia Kordyl, Jolanta Długaszewska, Dorota Kamińska, Raphaël Schneider, Tomasz Osmałek","doi":"10.3390/pharmaceutics17091218","DOIUrl":"10.3390/pharmaceutics17091218","url":null,"abstract":"<p><p><b>Background:</b> Skin mycoses affect approximately 10% of the global population, and the range of effective topical antifungal agents remains limited. Voriconazole (VRC) is a broad-spectrum triazole with proven efficacy against drug-resistant fungal infections. This study aimed to develop and optimize VRC-loaded microemulsion (ME) polymer gels (Carbopol^®-based) for cutaneous delivery. Selected formulations also contained menthol (2%) as a penetration enhancer and potential synergistic antifungal agent. <b>Methods:</b> A comprehensive screening was performed using pseudoternary phase diagrams to identify stable oil/surfactant/co-surfactant/water systems. Selected MEs were prepared with triacetin, Etocas™ 35, and Transcutol^®, then gelled with Carbopol^®. Formulations were characterized for pH, droplet size, polydispersity index (PDI), and viscosity. In vitro VRC release was assessed using diffusion cells, while ex vivo permeation and skin deposition studies were conducted on full-thickness human skin. Rheological behavior (flow curves, yield stress) and texture (spreadability) were evaluated. Antifungal activity was tested against standard strain of <i>Candida albicans</i> and clinical isolates including a fluconazole-resistant strain. <b>Results:</b> The optimized ME (pH ≈ 5.2; droplet size ≈ 2.8 nm) was clear and stable with both VRC and menthol. Gelation produced non-Newtonian, shear-thinning hydrogels with low thixotropy, favorable for topical application. In ex vivo studies, performed with human skin, both VRC-loaded gels deposited the drug in the epidermis and dermis, with no detectable amounts in the receptor phase after 24 h, indicating retention within the skin. Menthol increased VRC deposition. Antifungal testing showed that VRC-containing gels produced large inhibition zones against <i>C. albicans</i>, including the resistant isolate. The VRC-menthol gel exhibited significantly greater inhibition zones than the VRC-only gel, confirming synergistic activity. <b>Conclusions:</b> ME-based hydrogels effectively delivered VRC into the skin. Menthol enhanced drug deposition and demonstrated synergistic antifungal activity with voriconazole.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145176710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theranostic Potential of a New ⁶⁴Cu-Labeled NOTA-R954 Peptide Conjugate for Kinin B1R Expressing Prostate Cancer.","authors":"Sadaf Ghanaatgar Kasbi, Martin Savard, Frédéric Couture, Céléna Dubuc, Véronique Dumulon-Perreault, Marie-Edith Nepveu-Traversy, Samia Ait-Mohand, Robert Sabbagh, Sameh Geha, Brigitte Guérin, Yves Dory, Fernand Gobeil","doi":"10.3390/pharmaceutics17091215","DOIUrl":"10.3390/pharmaceutics17091215","url":null,"abstract":"<p><p><b>Background/Objectives</b>: This study explores the potential of the inducible G protein-coupled kinin B1 receptor (B1R) as a target for the diagnosis and treatment of prostate cancer (PCa) and aims to develop the first theranostic agent targeting hB1R for both molecular imaging and radionuclide therapy. <b>Methods</b>: B1R expression was analyzed via qPCR and immunohistochemistry in human PCa cells and tissues specimens. A novel ⁶⁴Cu/NOTA-conjugated peptide analog of the potent B1R antagonist R954 was synthetized and evaluated in vitro and in vivo. <b>Results</b>: B1R was confirmed to be expressed (RNA, protein) by varying degrees in all PCa cell lines and tissues investigated, with protein level significantly correlating with tumor grades. This finding was supported by similar analyses from the TCGA and MSKCC databases. In vitro, the ⁶⁴Cu/NOTA-βAla-R954 conjugate showed nanomolar affinity/potency at hB1R, complete plasma stability over 24 h, significant cellular uptake (up to 33% of ID at 24 h), and dose-dependent anti-clonal growth effects. In vivo, the radioconjugate remained stable in circulation for up to 90 min and was primarily excreted intact via the kidneys following IV administration. Intravenous ⁶⁴Cu/NOTA-βAla-R954 (7.5 MBq) effectively detected subcutaneous PCa xenografts via µPET imaging in male athymic nude mice. At a single higher dose (65 MBq; 50 µg/kg), it significantly reduced tumor growth without observable toxicity. This antitumor effect was associated with increased apoptosis (active caspase-3) and reduced proliferation (Ki67), as shown by immunohistochemistry. In contrast, the nonradioactive ^NatCu/NOTA-βAla-R954 had no therapeutic effect at the same dose. <b>Conclusions</b>: Our findings provide proof-of-concept for the potential theranostic use of ⁶⁴Cu/NOTA-R954 in PCa, and potentially other types of B1R-positive solid cancers.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Industrial Sustainable Decrystallizing Formulation to Enhance Dissolution of Candesartan Cilexetil: Overcoming Limitations of Traditional Solid Dispersion Approaches.","authors":"Mohamed A Ibrahim, Abdelrahman Y Sherif, Doaa Hasan Alshora","doi":"10.3390/pharmaceutics17091214","DOIUrl":"10.3390/pharmaceutics17091214","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Conventional solid dispersion methods face significant industrial limitations, including thermal degradation, residual organic solvents, and complex preparation processes. This study presents a novel decrystallizing formulation using poloxamer and propylene glycol that remains solid during storage but liquefies at physiological temperature (37 °C). <b>Methods</b>: Decrystallizing formulations containing various poloxamer types (407 and 188) at different concentrations (5-25% w/w) were prepared and assessed for decrystallization temperature, decrystallization time, and drug solubility. The optimal formulation was further characterized using FTIR analysis, as well as in vitro liquefaction performance and dissolution studies. Finally, the industrial sustainability of the decrystallizing formulation was assessed against conventional methods. <b>Results</b>: Poloxamer 407 exhibited higher decrystallization temperature, longer decrystallization time, and superior solubilization capacity compared to Poloxamer 188. Maximum drug solubility (5.51 ± 0.08 mg/g) was achieved at 20% w/w of poloxamer 407 with a decrystallization temperature of 37 °C, and it took 216 s for decrystallization. FTIR spectroscopy confirmed hydrogen bonding interactions, which are responsible for temperature-dependent phase transitions. The decrystallizing formulation showed remarkable improvement in dissolution efficiency (80.6 ± 3.9%) compared to the raw drug (1.8 ± 0.8%), a physical mixture (11.1 ± 6.0%), and a marketed tablet (30.8 ± 2.2%). <b>Conclusions</b>: The current decrystallizing formulation offers a promising approach for improving the bioavailability of poorly water-soluble drugs and tackling the limitations of conventional methods. Moreover, it provides additional advantages in terms of industrial sustainability for continuous production compared to conventional approaches.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amino Compound-Synthesized Gold Nanoparticles for SARS-CoV-2 Antigen Delivery.","authors":"Layane Souza Rego, Marianna Teixeira Pinho Favaro, Monica Josiane Rodrigues-Jesus, Robert Andreata-Santos, Luiz Mário Ramos Janini, Marcelo Martins Seckler, Luis Carlos de Souza Ferreira, Adriano Rodrigues Azzoni","doi":"10.3390/pharmaceutics17091211","DOIUrl":"10.3390/pharmaceutics17091211","url":null,"abstract":"<p><p><b>Background:</b> Gold nanoparticles (AuNPs) are a promising platform for vaccine antigen delivery due to their ability to stimulate both innate and adaptive immune responses. These effects depend strongly on physicochemical properties such as size, polydispersity, morphology, and surface charge, which are in turn determined by the synthesis method. While amino acids are often used as capping agents for AuNPs, their direct use as both reducing and stabilizing agents has been rarely investigated. <b>Objectives:</b> This study aimed to establish an ultrasound-assisted method for synthesizing AuNPs using amino compounds as both reducing and stabilizing agents, and assess their physicochemical characteristics, antigen-binding capacity, and immunogenicity. <b>Methods:</b> AuNPs were synthesized using L-cysteine, L-arginine, and cysteamine as dual reducing/stabilizing agents under ultrasonic conditions. The nanoparticles were combined with a recombinant receptor-binding domain (RBD) of SARS-CoV-2 and evaluated in mice for their ability to induce antibody responses. <b>Results:</b> The synthesized AuNPs exhibited hydrodynamic diameters ranging from 6.3 to 12.4 nm and zeta potentials from -40.5 to +36.5 mV, depending on the amino compound used. All formulations elicited robust anti-RBD IgG responses, but virus neutralization activity varied significantly. Notably, AuNP-arginine induced the strongest neutralizing response despite lower adsorption capacity and stability, suggesting that epitope preservation and antigen presentation quality were more decisive than antigen density. <b>Conclusions:</b> These findings underscore the importance of nanoparticle design in optimizing antigen presentation and highlight the potential of amino compound-synthesized AuNPs as effective antigen delivery vehicles for future vaccine development.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Salt Cocrystallization-A Method to Improve Solubility and Bioavailability of Dihydromyricetin.","authors":"Jingping Li, Xinke Chen, Yanan Liu, Caiwu Jiang","doi":"10.3390/pharmaceutics17091209","DOIUrl":"10.3390/pharmaceutics17091209","url":null,"abstract":"<p><p><b>Objectives</b>: This study aimed to find salts with similar pharmacological effects designed as cocrystals to improve the aqueous solubility and bioavailability of dihydromyricetin (DMY). <b>Methods</b>: A salt-cocrystal solvate (DMY-CIP·C₂H₆O) of dihydromyricetin and ciprofloxacin hydrochloride (CIP) was successfully prepared via solvent evaporation method, and further characterized using powder X-ray diffraction, thermal analysis, and infrared spectroscopy. The solubility, stability, bioavailability, and in vitro antimicrobial efficacy of the cocrystal were also studied. <b>Results</b>: The cocrystal could increase the solubility of DMY in water and greatly improve the absorption of DMY in vivo (8-fold enhancement in relative bioavailability). In addition, the in vitro antimicrobial efficacy of the cocrystal was comparable to that of CIP, which is a great improvement for DMY. However, due to the formation of cocrystals with salts, the humidity stability of DMY is reduced and it should not be stored in high-humidity environments. <b>Conclusions</b>: These findings demonstrate that cocrystallization with water-soluble salts represents an effective strategy for optimizing the pharmaceutical properties of poorly soluble compounds.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the Oral Mucosa: Emerging Drug Delivery Platforms and the Therapeutic Potential of Glycosaminoglycans.","authors":"Bruno Špiljak, Maja Somogyi Škoc, Iva Rezić Meštrović, Krešimir Bašić, Iva Bando, Ivana Šutej","doi":"10.3390/pharmaceutics17091212","DOIUrl":"10.3390/pharmaceutics17091212","url":null,"abstract":"<p><p>Research into oral mucosa-targeted drug delivery systems (DDS) is rapidly evolving, with growing emphasis on enhancing bioavailability and precision targeting while overcoming the unique anatomical and physiological barriers of the oral environment. Despite considerable progress, challenges such as enzymatic degradation, limited mucosal penetration, and solubility issues continue to hinder therapeutic success. Recent advancements have focused on innovative formulation strategies-including nanoparticulate and biomimetic systems-to improve delivery efficiency and systemic absorption. Simultaneously, smart and stimuli-responsive materials are emerging, offering dynamic, environment-sensitive drug release profiles. One particularly promising area involves the application of glycosaminoglycans, a class of naturally derived polysaccharides with excellent biocompatibility, mucoadhesive properties, and hydrogel-forming capacity. These materials not only enhance drug residence time at the mucosal site but also enable controlled release kinetics, thereby improving therapeutic outcomes. However, critical research gaps remain: standardized, clinically meaningful mucoadhesion/permeation assays and robust in vitro-in vivo correlations are still lacking; long-term stability, batch consistency of GAGs, and clear regulatory classification (drug, device, or combination) continue to impede scale-up and translation. Patient-centric performance-palatability, mouthfeel, discreet wearability-and head-to-head trials versus standard care also require systematic evaluation to guide adoption. Overall, converging advances in GAG-based films, hydrogels, and nanoengineered carriers position oral mucosal delivery as a realistic near-term option for precision local and selected systemic therapies-provided the field resolves standardization, stability, regulatory, and usability hurdles.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Glycyrrhiza uralensis</i> Polysaccharide Gold Nanoparticles as Antigen Carriers and Potential Adjuvant to DC Vaccines.","authors":"Yanan Zhao, Ming Song, Yilizilan Dilixiati, Shanshan Cai, Reyilanmu Maisaidi, Patanmu Aili, Jinyao Li, Lili Han, Adila Aipire","doi":"10.3390/pharmaceutics17091213","DOIUrl":"10.3390/pharmaceutics17091213","url":null,"abstract":"<p><p><b>Background</b>: Cervical cancer is the fourth leading cause of death among women worldwide, with human papillomavirus (HPV) identified as a major contributing factor. This study investigates the immunostimulatory activity and antigen delivery efficiency of <i>Glycyrrhiza uralensis</i> polysaccharide gold nanoparticles (GUPS-AuNPs) and assesses the antitumor efficacy of an HPV dendritic cell (DC) vaccine using GUPS-AuNPs as a delivery system. <b>Methods</b>: GUPS-AuNPs were synthesized via a green reduction method and characterized using advanced techniques, including SEM, EDS, TEM, UV, and FT-IR spectroscopy. DCs served as the primary experimental model, with flow cytometry employed to evaluate the immunostimulatory activity and antigen delivery effectiveness of GUPS-AuNPs. Additionally, a TC-1 tumor-bearing mouse model was established to assess the immunostimulatory and antitumor effects of the HPV-DC vaccine facilitated by GUPS-AuNPs. <b>Results</b>: The synthesized GUPS-AuNPs exhibited a particle size of 120.77 ± 3.13 nm, a surface charge of -11.9 ± 2.1 mV, and excellent stability. Flow cytometry analysis demonstrated that GUPS-AuNPs significantly enhanced DC maturation and promoted T cell proliferation. Furthermore, antigen delivery experiments revealed that GUPS-AuNPs improved the antigen capture capabilities of DCs. Confocal imaging confirmed that GUPS-AuNPs extended the intracellular retention time of antigens. In vivo studies showed that the HPV-DC vaccine formulated with GUPS-AuNPs as carriers effectively suppressed tumor growth, elevated the populations of CD4⁺ T and CD8⁺ T cells in the spleen, and induced a robust antigen-specific immune response. <b>Conclusions</b>: GUPS-AuNPs effectively enhance DC maturation and antigen delivery, significantly boosting the adaptive immune response triggered by HPV vaccines and leading to the inhibition of tumor progression. This research introduces GUPS-AuNPs as a novel, safe, and efficient antigen delivery platform with promising potential for vaccine development.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing Oral Absorption of an Ester Prodrug by Coating Drug Crystals with Binary Lipid Systems and Evaluating the Influence of Compositions.","authors":"Xiaowei Dong, Tao Zhang, Hellen L Moreno Sanchez, Jaylen C Mans, Sung Hun Bae, Liangqiao Bian","doi":"10.3390/pharmaceutics17091210","DOIUrl":"10.3390/pharmaceutics17091210","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Prodrug strategies are a vital aspect of drug development, with ester prodrugs particularly notable for modifying parent drug properties through ester functional groups to enhance oral absorption. However, ester prodrugs are prone to hydrolysis by water and enzymes, making stability in the gastrointestinal (GI) tract prior to absorption a key challenge. Few formulation strategies effectively address this degradation issue. We recently introduced binary lipid systems (BLS), comprising a lipid and a water-soluble surfactant only that form stable microemulsions. This study aimed to explore the application of BLS for enhancing the oral absorption of ester prodrugs by coating drug crystals with BLS in solid granules and study the impact of the compositions of BLS on oral absorption. <b>Methods</b>: Olmesartan medoxomil (OLM), a methyl ester prodrug of olmesartan (OL), was selected as a model drug. Various lipids were combined with TPGS to form BLS and used to prepare OLM solid granules containing OLM crystals. <b>Results</b>: Among the tested formulations, OLM MCM-TPGS granules significantly enhanced drug release and protected OLM from enzyme-mediated degradation in two-step dissolution studies with esterase. Pharmacokinetic and tissue distribution studies in rats confirmed that OLM MCM-TPGS granules improved oral absorption by 145% and increased tissue uptake compared to OLM powder. <b>Conclusions</b>: This approach overcomes solubility limitations when using lipids and surfactants as excipients, enabling high drug loading in solid dosage forms and expanding the utility of lipids and surfactants for water-insoluble drugs. This novel formulation strategy holds great potential for enhancing oral absorption of ester prodrugs, representing a significant advancement in formulation technologies and offering more effective and versatile drug delivery solutions.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Risk-Based Framework for Hospital Compounding: Integrating Degradation Mechanisms and Predictive Toxicology.","authors":"Philippe-Henri Secretan, Maxime Annereau, Bernard Do","doi":"10.3390/pharmaceutics17091202","DOIUrl":"10.3390/pharmaceutics17091202","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Hospital compounding is essential for the delivery of patient-tailored therapies-particularly for pediatric and oncology patients and other groups requiring precise dosing. Its role is expected to grow as, for instance, the UK MHRA's new Guidance on Decentralised Manufacturing promotes alternative manufacturing pathways that integrate hospital preparation units. However, drug substances that remain stable in commercial oral formulations may undergo rapid degradation under alternative conditions (e.g., aqueous suspension, light exposure, or in the presence of specific excipients). Despite these risks, formulation strategies in hospital compounding often rely on empirical practices and lack structured guidance regarding stability, impurity control, and reproducibility. <b>Methods</b>: This study proposes a risk-based scientific framework for formulation design, integrating degradation profiling with predictive toxicology. Potential degradation pathways (hydrolytic, oxidative, and photolytic) are systematically identified through forced-degradation studies combined with ab initio modeling. These risks are translated into formulation strategies using a structured decision tree encompassing solvent selection, pH adjustment, excipient compatibility, and packaging considerations, even in the absence of a pharmacopeial monograph. The toxicological relevance of degradation products is evaluated using in silico approaches aligned with ICH M7 guidelines, thereby defining critical quality attributes (cQAs) and critical process parameters (CPPs). <b>Results</b>: The applicability of the framework is demonstrated through hospital compounding case studies, with further extension toward advanced applications such as semi-solid extrusion (SSE) 3D printing. <b>Conclusions</b>: By integrating mechanistic understanding of drug degradation into formulation planning, the proposed framework enhances the safety, reproducibility, and quality of compounded preparations. This approach reinforces Good Preparation Practices (GPPs) and is consistent with international quality-by-design (QbD) principles in the context of personalized medicine.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}