RSC Pharmaceutics最新文献

{"title":"Ion pairing as a strategy to enhance the delivery of diclofenac","authors":"Mignon Cristofoli, Jonathan Hadgraft, Majella E. Lane and Bruno C. Sil","doi":"10.1039/D5PM00096C","DOIUrl":"https://doi.org/10.1039/D5PM00096C","url":null,"abstract":"<p >This study explores the use of ion pairing and solvent selection to enhance the percutaneous delivery of diclofenac (DF) from topical formulations. Previous investigations identified <small>L</small>-histidine monochloride monohydrate (LHSS) as an ion pair candidate for diclofenac sodium (DNa). Initial <em>in vitro</em> permeation tests (IVPT) demonstrated that while LHSS increased DF permeation, it caused DF precipitation at higher concentrations. As DNa is sparingly soluble in water, the only solvent in which LHSS dissolves, its solubility was tested in alternative solvents. The highest solubility was observed in Transcutol® (TC), dipropylene glycol (DiPG) and propylene glycol (PG). Building on earlier research using TC : water binary systems to evaluate ion pairs, this study assessed: (i) the substitution of TC with DiPG in binary formulations, (ii) the development of ternary systems comprising water, TC and either DiPG or PG, and (iii) their impact on DF delivery using finite dose IVPT with porcine skin. The inclusion of LHSS (10 mg mL<small>⁻¹</small>) with DNa (10 mg mL<small>⁻¹</small>) in a DiPG : water (60 : 40 v/v) binary system significantly enhanced DF delivery (2.69 ± 1.01%), relative to the LHSS-free control (1.02 ± 0.44%, <em>p</em> &lt; 0.05.). However, this was significantly lower than in TC : water binary formulations (4.80 ± 1.08–5.41 ± 2.21%; <em>p</em> &lt; 0.05). Similarly, the ternary formulation containing DiPG (5 mg mL<small>⁻¹</small> DNa; 12.5 mg mL<small>⁻¹</small> LHSS; DiPG : TC : water; 10 : 40 : 50 v/v/v) resulted in lower DF delivery (5.62 ± 2.78%) compared to the corresponding TC : water (50 : 50 v/v) binary formulation (12.26 ± 3.06%, 5 mg mL<small>⁻¹</small> DNa; 12.5 mg mL<small>⁻¹</small> LHSS, <em>p</em> &lt; 0.05). Conversely, replacing DiPG with PG in the ternary formulation (PG : TC : water; 10 : 40 : 50 v/v/v) containing 25 mg mL<small>⁻¹</small> LHSS, significantly enhanced DF permeation (4.26 ± 1.41 μg cm<small>⁻²</small>) compared to all binary (0.14 ± 0.28–1.52 ± 0.32 μg cm<small>⁻²</small>) and ternary formulations (0.21 ± 0.36–1.72 ± 1.06 μg cm<small>⁻²</small>, <em>p</em> &lt; 0.05). This formulation also outperformed a recognised commercial product (1.74 ± 0.6 μg cm<small>⁻²</small>) by 145%, despite containing only half the DNa concentration and resulted in the highest total DF uptake as a percentage of the applied dose (27.25 ± 2.61%). This work builds on previous findings, confirming that LHSS enhances DF delivery in combination with DNa. By examining solvent systems and counterion effects, it provides a deeper understanding of formulation strategies to optimise the percutaneous delivery of DF.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 5","pages":" 1163-1174"},"PeriodicalIF":0.0,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm00096c?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145073485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential of small extracellular vesicles for pancreatic cancer therapy","authors":"Richard Crow, Oksana Kehoe and Clare Hoskins","doi":"10.1039/D5PM00115C","DOIUrl":"https://doi.org/10.1039/D5PM00115C","url":null,"abstract":"<p >Extracellular vesicles come in various shapes and sizes and are released by most cell types. They have myriad roles in intercellular signalling in both physiological and pathological environments, carrying a range of lipids, proteins and nucleic acids. Their cargo is then unloaded at the target site inducing a change in their target cell. Cancers use these vesicles to their advantage for a wide range of outcomes such as immune evasion and chemoresistance leading to the reduced effect of chemotherapies and unfavourable patient outcomes. Pancreatic cancer has one of the worst outcomes of any cancer with surgery being the only cure. As surgery is only available in a small number of cases, targeted delivery of cargos directly to the tumour site is of high importance to efficiently target and destroy cancer cells with high effectiveness without the toxic off-target effects of chemotherapy drugs. Hijacking the body's postal system has gained interest in the last decade for the delivery of therapeutic drugs. The low immunogenicity and inherent biocompatibility of extracellular vesicles avoids the hurdles experienced by other nanoparticles such as toxicity. Various techniques for loading and functionalising extracellular vesicles have progressed to clinical trials, however, these therapies are yet to make it onto the market. This review seeks to be a call to action to the pancreatic cancer community, highlighting the potential of these biologic systems in the improvement of therapeutic outcomes of what is one of the deadliest cancers.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 5","pages":" 1034-1049"},"PeriodicalIF":0.0,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm00115c?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145073572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging drug delivery strategies for glaucoma therapy: focus on nanoparticles and stimuli-responsive systems","authors":"Sourabh Kundu, Gitika Kumari and Dadi A. Srinivasarao","doi":"10.1039/D5PM00068H","DOIUrl":"https://doi.org/10.1039/D5PM00068H","url":null,"abstract":"<p >Glaucoma is a progressive and chronic eye complication characterized by elevated intraocular pressure (IOP) and consequential optic nerve damage, ultimately leading to blindness. Current therapeutic interventions mainly focus on frequent topical administration of IOP-lowering agents. However, ocular tissues cause prompt clearance of the administered drugs, thereby leading to low bioavailability and reduced patient compliance. This necessitates the development of advanced delivery systems that not only enhance the ocular residence of therapeutic agents but also govern drug release at the site of interest in a spatiotemporally controlled manner. The emergence of nanomedicine and stimuli-responsive delivery systems partially helped to achieve these objectives. These systems show improved permeability, longer ocular retention, or stimuli-responsive drug release (against specific triggers like temperature, pH, ion or enzymes), thereby offering on-demand drug release at the site of interest. This review discusses the anatomy and physiology of ocular tissues, emphasizing their barrier properties for drug delivery in glaucoma therapy. The challenges associated with conventional drug delivery approaches, routes of drug administration, and the need for the development of advanced drug delivery systems have also been emphasized. Furthermore, recent advances in the development of polymeric ophthalmic drug delivery systems and formulation strategies are mentioned with a special emphasis on nanoparticles, <em>in situ</em> gels, and stimuli-responsive systems. Finally, we present our perspectives on scale-up issues, regulatory hurdles, and clinical translation of advanced drug delivery systems.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 5","pages":" 1050-1077"},"PeriodicalIF":0.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm00068h?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145073540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intratumoral microbiota: a new perspective in cancer initiation, development, and therapy","authors":"Huiling Liu, Zhonghui Luo, Fangzhen Luo, Xilian Wang, Hua Wei and Cui-Yun Yu","doi":"10.1039/D5PM00045A","DOIUrl":"https://doi.org/10.1039/D5PM00045A","url":null,"abstract":"<p >Microbes have been identified as significantly impacting human health. Considerable attention has been focused on how microbiota affects cancer initiation, development, and therapeutic response. Currently, the biological functions of intratumoral microbiota have been preliminarily elucidated in tumors with high microbial abundance. However, the biological roles of the microbiota and their clinical significance in tumors with low microbial abundance, to our knowledge, remain largely unexplored. This gap in understanding is primarily due to the limited sensitivity of current detection technologies. This review provides a detailed examination of intratumoral microbiota characteristics and their interactions with the tumor microenvironment, focusing on the microbiota composition in various systems and its clinical role in different tumor types. Furthermore, the review explores the potential applications of intratumoral microbiota in cancer immunotherapy, including their role as immune enhancers, new drug delivery targets, and anticancer therapeutic agents. In conclusion, these insights may facilitate the use of microbiota for cancer diagnosis, prognosis, and the development of new therapeutic strategies.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 5","pages":" 865-881"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm00045a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145073487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accelerating safer administration of medicines to children in low resource settings – bridging stakeholder viewpoints","authors":"Sifan Hu, Alka Mukne, Vandana Patravale, Pradeep Behera, Krishnarajan Bangarurajan, Esmerald Hermans, Jennifer Walsh and Smita Salunke","doi":"10.1039/D5PM00133A","DOIUrl":"https://doi.org/10.1039/D5PM00133A","url":null,"abstract":"<p >Accurate medicine administration <em>via</em> the appropriate route is crucial, with oral liquids requiring dosing devices for precision and inhalation therapy depending on well-designed devices to ensure proper drug delivery. Hence, a workshop was held to understand the uptake of already existing administration devices for oral and respiratory medicines in low- and middle-income countries (LMICs), and to assess the level of awareness of issues associated with use of administration devices as well as the need for innovative devices. Discussions and knowledge shared during this event showed the effectiveness of the workshop in fostering a deeper understanding of the issues regarding use and development of administration devices in low resource settings.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 5","pages":" 1155-1162"},"PeriodicalIF":0.0,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm00133a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145073546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clobetasol propionate and pramoxine hydrochloride loaded nanolipid carrier gel for the treatment of atopic dermatitis†","authors":"Akhil Suresh, K. V. Navyasree, M. S. Sreelakshmi and Vidya Viswanad","doi":"10.1039/D5PM00048C","DOIUrl":"https://doi.org/10.1039/D5PM00048C","url":null,"abstract":"<p > <em>Aim.</em> To prepare and evaluate clobetasol propionate (CP) and pramoxine hydrochloride (PH) loaded nanolipid carrier (NLC)-based gel for improved skin permeation in the treatment of atopic dermatitis. <em>Methodology.</em> CP and PH-loaded NLCs were prepared by the melt emulsification ultrasonication technique<em>. In vitro</em>, <em>ex vivo</em>, and <em>in vivo</em> studies in the atopic dermatitis animal model of formulated drug-loaded NLC (DNLC) gel were evaluated. Dermal pharmacokinetic parameters were evaluated by Phoenix WinNonlin software. <em>Results and discussions</em>. DNLC gel was prepared successfully. Skin permeation and retentive property of the DNLC gel showed that CP from the DNLC had a permeability flux of 5.88 μg cm<small>⁻²</small> h<small>⁻¹</small> and an enhancement ratio of 1.92 compared to a CP drug solution, while PH from the DNLC gel had a permeability flux of 9.52 μg cm<small>⁻²</small> h<small>⁻¹</small> and an enhancement ratio of 1.62 compared to a PH drug solution. Dermal pharmacokinetic parameters were determined using WinNonlin software. CP retention at 24 h in stratum corneum, epidermis, and dermis was 4.25 ± 0.02 μg, 75.77 ± 0.01 μg, and 32.04 ± 0.012 μg, respectively, while PH retention at 24 h was 11.82 ± 0.003 μg, 344.0 ± 0.05 μg, and 172.85 ± 0.040 μg, respectively. More CP was retained from the DNLC gel than that from marketed CP cream. <em>In vivo</em> animal studies confirmed the effectiveness of DNLC gel in treating atopic dermatitis compared to commercial cream and individual drug-loaded DNLC gel, decreasing induced disease on a par with marketed CP cream. Epidermal thickness, immunoglobin E (IgE), and absolute eosinophil count (AEC) showed the greatest reduction in the DNLC gel treatment group.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 5","pages":" 1175-1188"},"PeriodicalIF":0.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm00048c?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145073486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new strategy for the extrahepatic delivery of lipid-based nanomedicines: a protein corona-mediated selective targeting system based on an ionizable cationic lipid library","authors":"Mahmoud A. Younis, Yusuke Sato, Seigo Kimura and Hideyoshi Harashima","doi":"10.1039/D5PM00079C","DOIUrl":"https://doi.org/10.1039/D5PM00079C","url":null,"abstract":"<p >Applying lipid nanoparticle (LNP) technology to ribonucleic acid (RNA) nanomedicines was integral to the success of mRNA vaccines against COVID-19. To expand the power of LNP technology, extrahepatic delivery systems have been developed using specific ligands that target the cells in question. However, recent increases in evidence support targeting without the need to attach specific ligands to nanocarriers. In this review, we focused on protein corona-mediated extrahepatic delivery of nanoparticles as an alternative to classic ligand-mediated active targeting. First, the interaction of LNPs with biological components and the impact that the physicochemical properties of LNPs exert on their biological fate are discussed. Then, we highlight a new system that targets activated hepatic stellate cells (aHSCs) as a successful model achieved through intensive optimization of LNPs based on an ionizable cationic lipid library. We also discuss cumulative evidence that support the ligand-free extrahepatic delivery of nanoparticles to a broad diversity of tissues, such as the spleen, lungs, brain, tumors, kidneys, placenta, pancreas, and bone marrow. In conclusion, we propose protein corona-mediated extrahepatic delivery as a new strategy of active targeting for RNA nanomedicines and inspire the future directions in this area.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 5","pages":" 982-1002"},"PeriodicalIF":0.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm00079c?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145073484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic screening of excipients to stabilize aerosolized lipid nanoparticles for enhanced mRNA delivery†","authors":"Brittany J. Heiser, Mae M. Lewis, Meysam Mohammadi Zerankeshi, Emily K. Netemeyer, Ashlee M. Hernandez, Alexander E. Marras and Debadyuti Ghosh","doi":"10.1039/D5PM00061K","DOIUrl":"10.1039/D5PM00061K","url":null,"abstract":"<p >Aerosolized lipid nanoparticles (LNPs) delivering mRNA are an attractive strategy for use in local, inhalable therapy to treat patients with lung diseases. However, a major barrier to delivering aerosolized mRNA LNPs is the shear forces encountered during aerosolization. These forces lead to significant morphology changes and subsequent decrease in efficacy of mRNA delivery. To best retain the physicochemical properties of mRNA LNPs during aerosolization, we took a formulation-based strategy to stabilize LNPs. We used a design-of-experiment (DOE) approach to comprehensively screen rationally chosen excipients at multiple concentrations. Excipients were carefully selected based on their use in clinically approved inhaled products or their ability to support lipid membrane properties. These excipients were added to the same mRNA LNP composition after formulation, were subsequently characterized, and used to transfect human lung cells at air–liquid interface. From this systematic screen, we identified that the addition of our lead candidate, poloxamer 188, best stabilizes LNP size throughout aerosolization and enhances mRNA expression after aerosolization. Additional morphological studies of the inclusion of poloxamer 188 in LNPs suggests that the excipient lowers aerosolization induced fusion or aggregation of particles without altering the internal structure. Our results indicate that poloxamer 188 can support aerosolized mRNA LNP delivery by maintaining LNP size and significantly enhancing therapeutic nucleic acid delivery to lung cells.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 5","pages":" 1139-1154"},"PeriodicalIF":0.0,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12272335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incorporating AI, in silico, and CRISPR technologies to uncover the potential of repurposed drugs in cancer therapy","authors":"Hend Gamal, Eman Mostafa Shoeib, Areej Hajjaj, Heba Elsafy Abdelaziz Abdullah, Esmail H. Elramy, Doaa Ahmed Abd Ellah, Shorouk Mahmoud El-Sayed and Mohammad Fadl Khder","doi":"10.1039/D5PM00158G","DOIUrl":"https://doi.org/10.1039/D5PM00158G","url":null,"abstract":"<p >Patients with cancer have faced exhausting physical and mental obstacles as a result of traditional treatment methods including chemotherapy and radiation therapy. In cancer, drug repurposing—the use of already-approved medications for novel therapeutic indications—has become a game-changing tactic. This method greatly lowers development costs and durations by utilizing the wealth of safety and pharmacokinetic data available for licensed medications. Large-scale databases and advanced computer techniques enable it to logically find either combinations of traditional medications or selective “non-selective” target medications. Furthermore, repurposing cancer drugs can undergo a significant and profound change thanks to genome-editing technologies like CRISPR-dCas9. It is recognized that there is yet unrealized potential of these advanced methods in further applications. Understanding the pros and cons of these technologies can provide valuable insights for clinical practice and fundamental research projects. This research will explore various innovative methods, including artificial intelligence (AI) algorithms, supervised machine learning (ML), data resources for <em>in silico</em>, microbial clustered regularly interspaced short palindromic repeats-dCas9 (CRISPR-dCas9) based artificial transcription factors, and combination therapy. This comprehensive guide outlines various methods for repurposing drugs, addressing effects, trials, barriers, and potential solutions to aid clinicians and researchers in maximizing efficacy and efficiency.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 5","pages":" 1019-1033"},"PeriodicalIF":0.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm00158g?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145073571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Release performance and crystallization of racemic and enantiopure praziquantel amorphous solid dispersion in various media†","authors":"Benedito Roberto de Alvarenga Junior and Lynne S. Taylor","doi":"10.1039/D5PM00117J","DOIUrl":"https://doi.org/10.1039/D5PM00117J","url":null,"abstract":"<p >Praziquantel (PZQ) is the first-line treatment for schistosomiasis, but its low aqueous solubility and extensive first-pass metabolism limit PZQ's bioavailability. Furthermore, the commercial formulation of PZQ includes the inactive (<em>S</em>)-PZQ enantiomer, which causes unwanted side effects and a bitter taste. This work aimed to evaluate the impact of chirality on PZQ's performance in amorphous solid dispersion (ASD) formulations prepared from both racemic and the active (<em>R</em>)-PZQ enantiomer, with additional studies on polymer type and processing method. ASDs of (<em>R</em>,<em>S</em>)-PZQ and (<em>R</em>)-PZQ at 30% drug loading were prepared with HPMCAS MF and HPMC E5 <em>via</em> solvent evaporation (SE) and hot-melt extrusion (HME). Release testing was conducted in aqueous media with different pH values and in biorelevant media simulating fasted- and fed-state conditions. Results demonstrated that ASDs significantly enhanced PZQ concentrations, with the amorphous solubility being up to 8-fold higher than that of the corresponding crystalline form. HPMCAS-based ASDs showed pH-dependent release, with poor release at gastric pH but achieving near-complete release with crystallization inhibition at intestinal pH conditions, while HPMC-based ASDs exhibited faster gastric release but reduced stability due to crystallization, which was confirmed by polarized light microscopy (PLM) and powder X-ray diffraction (PXRD). (<em>R</em>)-PZQ-HPMCAS ASDs outperformed (<em>R</em>,<em>S</em>)-PZQ-HPMCAS ASDs in simple media at pH 6.5 at high target concentration, which was attributed to a slightly higher amorphous solubility. However, both ASDs exhibited comparable release in fasted-state media due to bile salt-enhanced solubility. PZQ-ASDs showed crystallization when evaluated in FeSSIF-V2 and did not release well. Different processing methods minimally affected release profiles, highlighting HME's potential as a scalable, solvent-free method. These findings suggest that (<em>R</em>)-PZQ-HPMCAS is a promising alternative to commercial racemic PZQ formulations, potentially reducing side effects and improving patient compliance through allowing for a reduced pill burden.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 5","pages":" 1125-1138"},"PeriodicalIF":0.0,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm00117j?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145073545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}