International Journal of Pharmaceutics: X最新文献

{"title":"HSPiP and QbD oriented optimized stearylamine-elastic liposomes for topical delivery of ketoconazole to treat deep seated fungal infections: In vitro and ex vivo evaluations","authors":"Afzal Hussain,&nbsp;Mohammad A. Altamimi,&nbsp;Yaser Saleh Alneef","doi":"10.1016/j.ijpx.2024.100279","DOIUrl":"10.1016/j.ijpx.2024.100279","url":null,"abstract":"<div><p>The study explored stearylamine containing cationic elastic liposomes to improve topical delivery and efficacy of ketoconazole (KETO) to treat deeply seated fungal infections. Stearylamine was used for dual functionalities (electrostatic interaction and flexibility in lipid bilayer). Hansen solubility program (HSPiP) estimated Hansen solubility parameters (HSP) based on the SMILE file and structural properties followed by experimental solubility study to validate the predicted values. Various formulations were developed by varying phosphatidylcholine and surfactants (tween 80 and span 80) concentration. To impart cationic properties, stearylamine (1.0 %) was added into the organic phase. Using quality by design (QbD) method, we optimized the formulations and evaluated for vesicle size, polydispersity index, zeta potential, morphology (scanning electron microscopy), in vitro drug release (%), and ex vivo permeation profiles. Result showed that there is a good correlation (0.65) between HSPiP predicted and actual experimental solubility of KETO in water, chloroform, S80, and tween 80. Spherical OKEL1 showed an established correlation between the predicted and the actual formulation parameters (size, zeta potential, and polydispersity index) (259 nm vs 270 nm, +2.4 vs 0.21 mV, and 0.24 vs 0.27). OKEL1 was associated with the highest value of %EE (83.1 %) as compared to liposomes. Finally, OKEL1 exhibited the highest % cumulative permeation (49.9 %) as compared to DS (13 %) and liposomes (25 %). Moreover, OKEL1 resulted in 4-fold increase in permeation flux as compared to DS which may be attributed to vesicular mediated improved permeation and gel based compensated trans epidermal water loss in the skin. The drug deposition elicited OKEL1 and OKEL1-gel as suitable carriers for maximum therapeutic benefit to treat deeply seated fungal infections.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100279"},"PeriodicalIF":5.2,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590156724000513/pdfft?md5=4986714eeb3d26c7bfbabef529ffcfa3&pid=1-s2.0-S2590156724000513-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142098469","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":"Off-the-shelf medication transformed: Custom-dosed metoprolol tartrate tablets via semisolid extrusion additive manufacturing and the perception of this technique in a hospital context","authors":"Valerie R. Levine ,&nbsp;Mattias Paulsson ,&nbsp;Maria Strømme ,&nbsp;Julian Quodbach ,&nbsp;Jonas Lindh","doi":"10.1016/j.ijpx.2024.100277","DOIUrl":"10.1016/j.ijpx.2024.100277","url":null,"abstract":"<div><p>Pharmacies are currently unable to stock proper oral dosage forms for pediatric populations. This leads to manipulation of medications or the need to compound specialized medications, which can be a time-consuming process. Using Semisolid Extrusion (SSE) additive manufacturing (AM), specialized medications can be produced in an expedited process from off-the shelf medication in a hospital or outpatient pharmacy setting. In this study, tablets with a desired dose of 5 mg of metoprolol tartrate derived from commercial Seloken™ 50 mg tablets were 3D printed in a hospital setting. Validation testing was done on five batches, highlighting tablets with a high uniformity in mass and dimension, drug content, acceptable microbial assays, and prolonged release during in-vitro analysis. The average drug content found for the tablets was within ±6% of 5 mg for all batches produced. Comparisons were done between the SSE tablets and capsules produced in an external compounding facility, highlighting several positive aspects of SSE-produced tablets beyond simply shortening the production timeline. The SSE tablets printed in this study are characterized by their smaller size, enhanced prolonged release properties, and more uniform drug content across the tested samples. Additionally, interviews with pharmaceutical professionals were conducted to determine the positive aspects of SSE and further improvements to bring this technique as seamlessly as possible into the pharmacy. This study underscores the feasibility of employing SSE in the production of specialized medications within a hospital environment. Furthermore, it highlights the methodological advantages SSE offers over existing production standards, demonstrating its potential to improve pharmaceutical manufacturing in healthcare settings.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100277"},"PeriodicalIF":5.2,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590156724000495/pdfft?md5=b27a835df09636295206ed920aaa5d28&pid=1-s2.0-S2590156724000495-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142050251","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":"Platelet Membrane-Encapsulated Poly(lactic-co-glycolic acid) Nanoparticles Loaded with Sildenafil for Targeted Therapy of Vein Graft Intimal Hyperplasia","authors":"Fajing Yang ,&nbsp;Yihui Qiu ,&nbsp;Xueting Xie ,&nbsp;Xingjian Zhou ,&nbsp;Shunfu Wang ,&nbsp;Jialu Weng ,&nbsp;Lina Wu ,&nbsp;Yizhe Ma ,&nbsp;Ziyue Wang ,&nbsp;Wenzhang Jin ,&nbsp;Bicheng Chen","doi":"10.1016/j.ijpx.2024.100278","DOIUrl":"10.1016/j.ijpx.2024.100278","url":null,"abstract":"<div><p>Autologous vein grafts have attracted widespread attention for their high transplantation success rate and low risk of immune rejection. However, this technique is limited by the postoperative neointimal hyperplasia, recurrent stenosis and vein graft occlusion. Hence, we propose the platelet membrane-coated Poly(lactic-<em>co</em>-glycolic acid) (PLGA) containing sildenafil (PPS). Platelet membrane (PM) is characterised by actively targeting damaged blood vessels. The PPS can effectively target the vein grafts and then slowly release sildenafil to treat intimal hyperplasia in the vein grafts, thereby preventing the progression of vein graft restenosis. PPS effectively inhibits the proliferation and migration of vascular smooth muscle cell (VSMCs) and promotes the migration and vascularisation of human umbilical vein endothelial cells (HUVECs). In a New Zealand rabbit model of intimal hyperplasia in vein grafts, the PPS significantly suppressed vascular stenosis and intimal hyperplasia at 14 and 28 days after surgery. Thus, PPS represents a nanomedicine with therapeutic potential for treating intimal hyperplasia of vein grafts.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100278"},"PeriodicalIF":5.2,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590156724000501/pdfft?md5=3d845205751fe068fe01735728d463c6&pid=1-s2.0-S2590156724000501-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142050248","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":"M1 macrophage-membrane-cloaked paclitaxel/β-elemene nanoparticles targeting cervical cancer for enhanced therapy","authors":"Yi Wang ,&nbsp;Jiakun Wang ,&nbsp;Chengbo Huang ,&nbsp;Yang Ding ,&nbsp;Leyao Lv ,&nbsp;Yuhao Zhu ,&nbsp;Nuo Chen ,&nbsp;Yingyi Zhao ,&nbsp;Qing Yao ,&nbsp;Shengjie Zhou ,&nbsp;Mei Chen ,&nbsp;Qibing Zhu ,&nbsp;Lifeng Li ,&nbsp;Fengyun Chen","doi":"10.1016/j.ijpx.2024.100276","DOIUrl":"10.1016/j.ijpx.2024.100276","url":null,"abstract":"<div><p>Cervical cancer is a leading cause of cancer-related mortality in females worldwide, necessitating urgent solutions for effective treatment. Paclitaxel (PTX), a natural diterpene alkaloid compound, has the ability to inhibit mitosis and induce programmed apoptosis in tumor cells. However, its toxicity and drug resistance limit its efficacy in certain cervical cancer patients. β-elemene (β-ELE) can reverse multidrug resistance by inhibiting ATP-binding cassette transporters, thereby enhancing chemotherapy drug retention. Therefore, we propose a combination therapy using PTX/β-ELE to improve chemotherapy sensitivity. To enhance targeted drug delivery, we developed M1-macrophage-membrane-coated nanoparticles (M1@PLGA/PTX/β-ELE) for co-delivery of PTX&amp;β-ELE. Through both <em>in vitro</em> and <em>in vivo</em> cervical cancer models, we demonstrated that M1@PLGA/PTX/β-ELE effectively suppressed tumor progression and polarization of tumor-associated macrophages. Furthermore, H&amp;E staining confirmed the high therapeutic biosafety of M1@PLGA/PTX/β-ELE as there was no significant damage observed in major organs throughout the entire therapeutic process. Overall, this study presents a targeted biomimetic nanoplatform and combinatorial strategy that synergistically enhances chemosensitivity in malignant tumors.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100276"},"PeriodicalIF":5.2,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590156724000483/pdfft?md5=428acdc9d41659fed71ace04dce58008&pid=1-s2.0-S2590156724000483-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142050249","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":"Systematic investigation of the impact of screw elements in continuous wet granulation","authors":"Katharina Kiricenko ,&nbsp;Robin Meier ,&nbsp;Peter Kleinebudde","doi":"10.1016/j.ijpx.2024.100273","DOIUrl":"10.1016/j.ijpx.2024.100273","url":null,"abstract":"<div><p>Twin-screw wet granulation (TSG) is a continuous manufacturing technique either for granules as final dosage form or as an intermediate before tableting or capsule filling. A comprehensive process understanding is required to implement TSG, considering various parameters influencing granule and tablet quality. This study investigates the impact of screw configuration on granule properties followed by tableting, using a systematic approach for lactose-microcrystalline cellulose (lactose-MCC) and ibuprofen-mannitol (IBU) formulations. The most affecting factor, as observed by other researchers, was the L/S ratio impacting the granule size, strength and tabletability. Introducing tooth-mixing-elements at the end of the screw, as for the IBU formulation, resulted in a high proportion of oversized granules, with values between 36% and 78%. Increasing the thickness of kneading elements (KEs) produced denser, less friable granules with reduced tablet tensile strength. Granulation with more KEs, larger thickness or stagger angle increased torque values and residence time from 30 to 65 s. Generally, IBU granules exhibited high tabletability, requiring low compression pressure for sufficient tensile strength. At a compression pressure of 50 MPa, IBU tablets where at least one kneading zone was included resulted in approximately 2.5 MPa compared to lactose-MCC with 0.5 MPa. In conclusion, the TSG process demonstrated robustness by varying the screw design with minimal impact on subsequent tableting processes.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100273"},"PeriodicalIF":5.2,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590156724000458/pdfft?md5=50c2e0eba51b5397b6492700e1af0989&pid=1-s2.0-S2590156724000458-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141964659","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":"Reactive oxygen species responsive double-locked liposome collaborative photodynamic therapy for reducing electrical conduction recurrence after radiofrequency catheter ablation","authors":"Ying Zhuge ,&nbsp;Gonghao Li ,&nbsp;Mingyue Sun ,&nbsp;Jiajia Zhang ,&nbsp;Jiafeng Zou ,&nbsp;Feng Gao ,&nbsp;Fang Wang","doi":"10.1016/j.ijpx.2024.100275","DOIUrl":"10.1016/j.ijpx.2024.100275","url":null,"abstract":"<div><p>Radiofrequency catheter ablation (RFCA) is the preferred technique for the treatment of atrial fibrillation, but the recovery of electrical conduction after ablation seriously endangers the health of patients. This study aimed to develop reactive oxygen species (ROS) responsive double-locked liposome collaborative photodynamic therapy (PDT) to target the ablation area and reduce the recovery of electrical conduction after ablation. The successful synthesis of β-cyclodextrin modified with phenylboronic acid pinacol ester (OCD) was confirmed by ¹H NMR and FT-IR. Furthermore, the successful synthesis of octadecylamine-modified indocyanine green (ICG-ODA) was confirmed by ¹H NMR and mass spectrometry. The ICG-ODA was encapsulated in liposomes to generate a double-locked hybrid liposome (ICG-ODA@rNP), which was subsequently characterized. Several properties of ICG-ODA@rNP were evaluated, including the drug release, targeting ability and ability to inhibit electrical conduction recurrence. Moreover, a model was constructed for the blockage of electrical conduction after RFCA in rabbits to further evaluate ICG-ODA@rNP. The preliminary safety evaluation of ICG-ODA@rNP was also performed. The ICG-ODA@rNP with a uniform particle size showed excellent storage stability. The nanoparticle can sensitively release drugs under ROS environment, and exhibits excellent photothermal effects. Furthermore, ICG-ODA@rNP can circulate for a long time <em>in vivo</em> and accumulate significantly in the ablation area. In a pacing test with a left atrial appendage (LAA), these nanoparticles, combined with PDT, reduced the ratio of electrical conduction recovery, which was confirmed by a hematoxylin and eosin (H&amp;E) test. Further molecular analysis revealed that ICG-ODA@rNP could increase RFCA-induced apoptosis and ROS levels. Specifically, ICG-ODA@rNP significantly increased the expression of Bax and cleaved caspase-3, and decreased the expression of Bcl-2. In addition, the excellent biosafety of the double-locked nanoparticle was verified. This study provides evidence that ICG-ODA@rNP, with the double lock characteristic and biosafety, which exhibits a targeting effect on RFCA-induced cardiac injury areas, which further reduce electrical conduction recovery in RFCA areas by collaborativing PDT.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100275"},"PeriodicalIF":5.2,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590156724000471/pdfft?md5=71f97ac9aaddeba98820d85a32cf7441&pid=1-s2.0-S2590156724000471-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142012267","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 examination of process models and model risk frameworks for pharmaceutical manufacturing","authors":"Thomas F. O'Connor ,&nbsp;Sharmista Chatterjee ,&nbsp;Johnny Lam ,&nbsp;Dolores Hernán Pérez de la Ossa ,&nbsp;Leticia Martinez-Peyrat ,&nbsp;Marcel H.N. Hoefnagel ,&nbsp;Adam C. Fisher","doi":"10.1016/j.ijpx.2024.100274","DOIUrl":"10.1016/j.ijpx.2024.100274","url":null,"abstract":"<div><p>Process models are a growing tool for pharmaceutical manufacturing process design and control. The Industry 4.0 paradigm promises to increase the amount of data available to understand manufacturing processes. Tools such as Artificial Intelligence (AI) might accelerate process development and allow better predictions of process trajectories. Several examples of process improvements realized through the application of process models have been shown in lyophilization, chromatography, fluid bed drying, bioreactor control, continuous direct compression, and wet granulation. An important consideration of implementing a process model is determining the impact of the model on the quality of the product and the risks associated with model maintenance over the product lifecycle. Several regulatory documents address risk-based considerations for process models. This work discusses existing risk-based frameworks for model validation and lifecycle maintenance that could aid the adoption of process models in pharmaceutical manufacturing. Hypothetical case studies illustrate the implications of applying a model risk framework to facilitate model validation and lifecycle maintenance in the manufacture of pharmaceuticals and biological products.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100274"},"PeriodicalIF":5.2,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S259015672400046X/pdfft?md5=9ffcd3019bddcac26895281a73457971&pid=1-s2.0-S259015672400046X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141951060","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":"Biopharmaceutical profiling of anti-infective sanggenons from Morus alba root bark for inhalation administration","authors":"Jacqueline Schwarzinger ,&nbsp;Sigrid Adelsberger ,&nbsp;Karin Ortmayr ,&nbsp;Sarah Luise Stellnberger ,&nbsp;Ammar Tahir ,&nbsp;Gabriela Hädrich ,&nbsp;Verena Pichler ,&nbsp;Judith M. Rollinger ,&nbsp;Ulrike Grienke ,&nbsp;Lea Ann Dailey","doi":"10.1016/j.ijpx.2024.100272","DOIUrl":"10.1016/j.ijpx.2024.100272","url":null,"abstract":"<div><p>Mulberry Diels-Alder-type adducts (MDAAs), isolated from <em>Morus alba</em> root bark, exhibit dual activity against viral and bacterial pathogens but show sobering efficacy following oral administration. Inhalation administration may overcome issues with oral bioavailability and improve efficacy for the treatment of respiratory infections. To assess the suitability of MDAAs for inhalation administration, physicochemical (e.g. pH, pK_a, logP, pH-dependent solubility) and biopharmaceutical (epithelial cytotoxicity, permeability, and uptake) properties of two bioactive MDAA stereoisomers sanggenon C (SGC) and sanggenon D (SGD) were evaluated as isolated natural compounds and within parent extracts (MA21, MA60). Despite their structural similarity, SGD exhibited a 10-fold higher solubility than SGC across pH 1.2–7.4, with slight increases at neutral pH. Both compounds were more soluble in isolated form than in the parent extracts. The more lipophilic SGC was found to be more cytotoxic when compared to SGD, indicating a better cellular penetration, which was confirmed by uptake studies. Nonetheless, SGC and SGD exhibited no measurable permeability across intact Calu-3 monolayers, highlighting their potential for increased lung retention and improved local anti-infective activity following inhalation administration. Results suggest that SGC and SGD in isolated form, rather than as extracts, are promising candidates for pulmonary drug delivery to treat lung infections.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100272"},"PeriodicalIF":5.2,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590156724000446/pdfft?md5=23c48052cbbfd0eed0d776058bca8b11&pid=1-s2.0-S2590156724000446-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141997631","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":"EVA implants for controlled drug delivery to the inner ear","authors":"Y. Bedulho das Lages ,&nbsp;N. Milanino ,&nbsp;J. Verin ,&nbsp;J.F. Willart ,&nbsp;F. Danede ,&nbsp;C. Vincent ,&nbsp;P. Bawuah ,&nbsp;J.A. Zeitler ,&nbsp;F. Siepmann ,&nbsp;J. Siepmann","doi":"10.1016/j.ijpx.2024.100271","DOIUrl":"10.1016/j.ijpx.2024.100271","url":null,"abstract":"<div><p>This study evaluated the potential of poly(ethylene vinyl acetate) (EVA) copolymers as matrix formers in miniaturised implants, allowing to achieve controlled drug delivery into the inner ear. Due to the blood-cochlea barrier, it is impossible to reliably deliver a drug to this tiny and highly sensitive organ in clinical practice. To overcome this bottleneck, different EVA implants were prepared by hot melt extrusion, altering the vinyl acetate content and implant diameter. Dexamethasone was incorporated as a drug with anti-inflammatory and anti-fibrotic activity. Its release was measured into artificial perilymph, and the systems were thoroughly characterised before and after exposure to the medium by optical and scanning electron microscopy, SEM-EDX analysis, DSC, X-ray powder diffraction, X-ray microtomography and texture analysis. Notably, the resulting drug release rates were much higher than from <em>silicone</em>-based implants of similar size. Furthermore, varying the vinyl acetate content allowed for adjusting the desired release patterns effectively: With decreasing vinyl acetate content, the crystallinity of the copolymer increased, and the release rate decreased. Interestingly, the drug was homogeneously distributed as tiny crystals throughout the polymeric matrices. Upon contact with aqueous fluids, water penetrates the implants and dissolves the drug, which subsequently diffuses out of the device. Importantly, no noteworthy system swelling or shrinking was observed for up to 10 months upon exposure to the release medium, irrespective of the EVA grade. Also, the mechanical properties of the implants can be expected to allow for administration into the inner ear of a patient, being neither too flexible nor too rigid.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100271"},"PeriodicalIF":5.2,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590156724000434/pdfft?md5=84cb68b692d4656d50737d87a39e0681&pid=1-s2.0-S2590156724000434-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142012268","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":"The pH-dependence of efflux ratios determined with bidirectional transport assays across cellular monolayers","authors":"Soné Kotze ,&nbsp;Kai-Uwe Goss ,&nbsp;Andrea Ebert","doi":"10.1016/j.ijpx.2024.100269","DOIUrl":"https://doi.org/10.1016/j.ijpx.2024.100269","url":null,"abstract":"<div><p>MDCK/Caco-2 assays serve as essential in vitro tools for evaluating membrane permeability and active transport, especially mediated by P-glycoprotein (P-gp). Despite their utility, challenges remain in quantifying active transport and using the efflux ratio (ER) to determine intrinsic values for active efflux. Such an intrinsic value for P-gp facilitated efflux necessitates knowing whether this transporter transports the neutral or ionic species of a compound. Utilising MDCK-MDR1 assays, we investigate a method for determining transporter substrate fraction preference by studying ER pH-dependence for basic, acidic and non-dissociating compounds. These results are compared with model fits based on various assumptions of transporter species preference. As an unexpected consequence of these assays, we also give evidence for an additional influx transporter at the basolateral membrane, and further extend our model to incorporate this transport. The combined influences of paracellular transport, the previously unaccounted for basolateral influx transporter, as well as potential pH effects on the transporter impedes the extraction of intrinsic values for active transport from the ER. Furthermore, we determined that using inhibitor affects the measurement of paracellular transport. While clear indications of transporter species preference remain elusive, this study enhances understanding of the MDCK system.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100269"},"PeriodicalIF":5.2,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590156724000410/pdfft?md5=836d8c4dc4474fe1aa86bde0b6c72993&pid=1-s2.0-S2590156724000410-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141607105","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}