International Journal of Pharmaceutics: X最新文献

{"title":"Tailored transethosomal systems for tadalafil transdermal delivery: Impact of Phosal and edge activators on skin permeation and cellular uptake","authors":"Turky Omar Asar ,&nbsp;Hossam S. El-Sawy ,&nbsp;Ahmed M. Reda ,&nbsp;Mohamed Ashraf ,&nbsp;Amer H. Asseri ,&nbsp;Abdelsattar M. Omar ,&nbsp;Tarek A. Ahmed ,&nbsp;Khalid M. El-Say","doi":"10.1016/j.ijpx.2025.100376","DOIUrl":"10.1016/j.ijpx.2025.100376","url":null,"abstract":"<div><div>Tadalafil (TDLF), a Biopharmaceutics Classification System (BCS) Class II drug, exhibits poor aqueous solubility and extensive first-pass metabolism, which limits its therapeutic efficacy. We developed Phosal-based transethosomes (TrEthOs) to overcome these challenges, thereby enhancing transdermal delivery. A Box-Behnken design was employed to optimize the formulation by evaluating the effects of Phosal type, polyethylene glycol (PEG) 400 concentration, and cholesterol content. The optimized TrEthOs exhibited a mean vesicle size of 129.74 nm and an entrapment efficiency of 67.3%, ensuring efficient encapsulation of the drug. <em>Ex vivo</em> permeation studies demonstrated a cumulative TDLF permeation of 70.24% over 6 hours, with a steady-state flux of 19.49 × 10^-4 mg/cm²·min. Confocal laser scanning microscopy confirmed deep skin penetration, while <em>in vitro</em> studies revealed significantly enhanced cellular uptake (P &lt; 0.0001) and reduced cytotoxicity (IC₅₀ = 67.61 μg/mL) compared to pure TDLF (IC₅₀ = 34.85 μg/mL). The novel Phosal-based TrEthOs system presents a promising transdermal drug delivery strategy, potentially reducing dosing frequency and improving patient compliance. These outcomes emphasize the potential of advanced nanocarrier systems to optimize systemic bioavailability while minimizing adverse effects.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100376"},"PeriodicalIF":6.4,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144866522","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":"Enhance therapeutic efficacy of BiTE (HER2/CD3) for HER2- positive tumors through in vivo expression","authors":"Huifang Zong ,&nbsp;Xi Li ,&nbsp;Yunxia Li ,&nbsp;Lei Wang ,&nbsp;Yali Yue ,&nbsp;Jie Chen ,&nbsp;Yong Ke ,&nbsp;Pameila Paerhati ,&nbsp;Lei Han ,&nbsp;Yijia Li ,&nbsp;Jianwei Zhu ,&nbsp;Baohong Zhang","doi":"10.1016/j.ijpx.2025.100375","DOIUrl":"10.1016/j.ijpx.2025.100375","url":null,"abstract":"<div><div>Bispecific T-cell engagers (BiTEs) are small-molecule antibodies that exhibits potent tumoricidal activity but suffer from a short plasma half-life. Mesenchymal stromal cells (MSCs) represent promising delivery vehicles for sustained therapeutic protein expression. In this study, we used human umbilical cord blood-MSCs (hUC-MSCs) as a delivery system to to secrete HER2/CD3 BiTE antibodies, thereby addressing the pharmacokinetic limitations of conventional BiTE therapies. HER2 amplification and overexpression are observed in multiple solid tumors, making it a potent target for anti-cancer therapies. Therefore, we constructed a BiTE targeting HER2 and CD3 as a model. <em>In vitro</em> efficacy, both MSCs and MSC-BiTE supernatants could induce significant cell death in BT474 and NCIN87 cells. <em>In vivo</em>, MSC-BiTE inhibited tumor growth in NCIN87 xenograft model. Furthermore, MSC-BiTE elevated the plasma levels of BiTE (HER2/CD3) antibody. Therefore, MSC-BiTE may be used as an efficient therapeutic agent for HER2-positive cancers.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100375"},"PeriodicalIF":6.4,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908610","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":"Stabilising large biologics through complimentary buffer component protection and rapid drying times","authors":"Laura Foley ,&nbsp;Marina Steiner-Browne ,&nbsp;Emmet O'Reilly","doi":"10.1016/j.ijpx.2025.100374","DOIUrl":"10.1016/j.ijpx.2025.100374","url":null,"abstract":"<div><div>High processing temperatures restrict spray drying applications for heat sensitive biologics. This work highlights the potential of Phosphate Buffer Saline (PBS) as the sole stabilising excipient when spray drying large biologics via a complimentary buffer component effect. Fibrinogen (∼340 kDa) was spray dried in PBS at various temperatures and concentrations, followed by assessment of the protein's structural integrity by UV–Vis, ATR-FTIR, SEM, and PXRD analyses. Experimental findings demonstrate that fibrinogen can maintain structural integrity when spray dried at temperatures up to 60 °C (T_out), when PBS is used as the sole stabilising excipient in combination with rapid drying rates. Results show a synergistic effect between the phosphate and salt components of the buffer when subjected to rapid drying rates mitigating protein aggregation and preserving protein secondary and tertiary structures. Stability studies conducted over 90 days indicated that powders stored under low humidity retained structural integrity. Findings provide valuable insights into the feasibility of spray drying large biologics through understanding the individual stabilising effects of PBS buffer components coupled with the rapid drying times. This approach offers a promising and scalable formulation strategy for the pharmaceutical industry in developing an alternative to freeze drying methods, offering advantages in cost, processing time, and product stability.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100374"},"PeriodicalIF":6.4,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144840995","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":"Platelet-rich plasma-contained drug delivery systems to treat orthopedic injuries","authors":"Mingdong Liu ,&nbsp;Jiaxin Ding ,&nbsp;Yanbo Peng ,&nbsp;Jialin Fang ,&nbsp;Man Zhao ,&nbsp;Wenyuan Zhang ,&nbsp;Haotian Chen ,&nbsp;Jian Zhang ,&nbsp;Haisheng Peng ,&nbsp;Qun Wang","doi":"10.1016/j.ijpx.2025.100372","DOIUrl":"10.1016/j.ijpx.2025.100372","url":null,"abstract":"<div><div>Orthopedic disorders affecting bones, joints, muscles, tendons, and other tissues are prevalent among outpatients, often caused by trauma, sports, or tumor removal. Surgical intervention is common but may yield unsatisfactory results due to limited regenerative capacity and poor blood supply. Platelet-rich plasma (PRP), an autologous biocomponent, has been clinically applied in tissue regeneration and repair, yet it faces challenges such as unclear mechanisms, side effects, and uncontrollable release. This review provides evidence for further clinical research on PRP and its associated drug delivery strategies in orthopedics. We searched multiple databases, including PubMed, Embase, Scopus, and Google Scholar databases Inclusion criteria focused on original studies containing the phrases (“orthopedic injuries,” “nanotechnology,” “microsphere,” or “drug delivery system”) and (“platelet-rich plasma”) over two decades to provide evidence to support further clinical research on PRP combined with nanotechnology in osteoarthritis, fractures, cartilage repair, and other orthopedic fields. Excluding criteria were referred to studies only describing “nanotechnology,” “microsphere,” or “drug delivery system”. In conclusion, PRP is a novel therapeutic tool for orthopedic diseases with advantages over traditional surgery. However, its clinical efficacy, action mechanisms, and preparation standards need further clarification. Future research should optimize PRP's therapeutic concentration, administration, and timing, and explore high-concentration PRP GFs as alternatives.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100372"},"PeriodicalIF":6.4,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144840994","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":"Advancing amorphous solid dispersions through empirical and hybrid modeling of drug–polymer solubility and miscibility: A case study using Ibuprofen","authors":"Matheus de Castro ,&nbsp;Ana Sara Cordeiro ,&nbsp;Mingzhong Li ,&nbsp;Christian Lübbert ,&nbsp;Catherine McColl ,&nbsp;Jatin Khurana ,&nbsp;Mark Evans ,&nbsp;Walkiria S. Schlindwein","doi":"10.1016/j.ijpx.2025.100373","DOIUrl":"10.1016/j.ijpx.2025.100373","url":null,"abstract":"<div><div>This study investigates the solubility and miscibility of ibuprofen (IBU) with four pharmaceutical polymers, KOLVA64®, KOL17PF®, HPMCAS, and Eudragit® EPO, using a combination of empirical and hybrid modeling approaches, supported by differential scanning calorimetry (DSC) experiments. Traditional group contribution methods based on Hildebrand and Hansen solubility parameters (Fedors, Hoftyzer–van Krevelen, and Just–Breitkreutz) showed variability in solubility predictions but consistently classified all polymer–API blends as miscible (Δδ &lt; 7<!--> <!-->MPa^½). Bagley plots reinforced these findings, although borderline miscibility was indicated for HPMCAS and EPO depending on the method used. A novel attempt to derive the Flory–Huggins (FH) interaction parameter (χ) from solubility parameters at near-melting temperatures showed poor agreement with experimental data, underscoring the limitations of such extrapolations and the semi-empirical nature of the FH model.</div><div>Phase diagrams were constructed from DSC-based melting point depression data using three modeling strategies: FH theory, the empirical approach by Kyeremateng (with two fitting methods), and the perturbed-chain statistical associating fluid theory (PC-SAFT) equation of state, both in pure predictions and with fitted binary interaction parameters (k_ij). The glass transition temperature (T_g) of the mixtures was modeled using the Gordon–Taylor and Kwei equations. All models provided a consistent polymer ranking based on their solubilizing capacity, with KOL17PF as the most compatible and HPMCAS as the least. Demixing zones (liquid-liquid equilibrium - LLE) predicted by FH and PC-SAFT models suggest that for HPMCAS-based ASDs only very low drug loadings (&lt; 5 % w/w) could potentially be stable at room temperature. In contrast, higher drug loadings (&gt; 10 % w/w) fall under a meta-stable zone with the other polymers, making them better candidates for IBU formulation. HPMCAS also exhibited consistently prediction errors across all T_g models, (AARD ∼4.5 %), indicating poorer agreement with experimental data. By integrating empirical and hybrid modeling approaches, this study highlights the strengths and limitations of commonly used solubility prediction methods and advocates for a shift toward a harmonized framework.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100373"},"PeriodicalIF":6.4,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144829939","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":"Integrative green synthesis and molecular simulation of ibrutinib cocrystals for enhanced biopharmaceutical performance and in vivo pharmacokinetics","authors":"Divya Dhatri Kara,&nbsp;Pragathi Devanand Bangera,&nbsp;Mahesha Keerikkadu,&nbsp;Mahalaxmi Rathnanand","doi":"10.1016/j.ijpx.2025.100371","DOIUrl":"10.1016/j.ijpx.2025.100371","url":null,"abstract":"<div><div>Bruton's tyrosine kinase (BTK) inhibitor, Ibrutinib (IBR), belongs to class II of the Biopharmaceutics Classification System (BCS). CYP3A4 enzyme forces IBR to have a very limited oral bioavailability. This study employed hot-melt extrusion (HME) with carboxylic and carboxamide coformers, guided by computational screening, to prepare and characterize IBR cocrystals (IBR-CC). Several carboxylic acid and carboxyl amide coformers were chosen in accordance with computational evaluations and predictions for the solubility parameter to formulate IBR-CC. According to the computational results, the formulated IBR-CC systems had multiple hydrogen bonds and π-π-stacking interactions. The IBR-CC formulations were further evaluated for powder dissolution studies, flow properties, and in vitro release studies. Furthermore, IBR-CC formulations were correlated with better anticancer action in K562-CCL-243 cancer cells when compared with IBR. From the in vivo pharmacokinetic evaluation studies, it was proven that the IBR oral bioavailability in IBR-Nicotinamide-cocrystal formulation has shown a 4.58-fold improvement, IBR-Fumaric acid-cocrystal formulation has shown a 2.66-fold improvement, and IBR-3-Hydroxy benzoic acid has shown a 1.76-fold enhancement when compared with pure IBR suspension. Biodistribution studies showed greater drug release in the intestine and other lymphoid organs when administered with IBR-Nicotinamide-cocrystal formulation than pure IBR suspension. As a result, the IBR-CC formulations produced utilizing the HME approach serve as an effective method of drug delivery that increases IBR's solubility and oral bioavailability.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100371"},"PeriodicalIF":6.4,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144810422","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":"Glucose-functionalized redox-responsive dihydroartemisinin prodrug nanosystem for targeted malaria therapy","authors":"Rongrong Wang ,&nbsp;Jiaqi Yang ,&nbsp;Jihong Qiang ,&nbsp;Qingxia Li ,&nbsp;Geng Wang ,&nbsp;Canqi Ping ,&nbsp;Kesheng Liu ,&nbsp;Ruili Wang ,&nbsp;Bin Zheng ,&nbsp;Guolian Ren ,&nbsp;Shuqiu Zhang","doi":"10.1016/j.ijpx.2025.100370","DOIUrl":"10.1016/j.ijpx.2025.100370","url":null,"abstract":"<div><div>Although malaria has been effectively controlled, it still poses a threat to global health. Artemisinins are the first-line antimalarial drugs. However, their therapeutic efficacy is significantly limited by poor solubility and short biological half-life. To overcome these limitations and enhance drug accumulation in <em>Plasmodium</em>, we developed a glucose-functionalized redox-responsive dihydroartemisinin (DHA) prodrug nanosystem (D@GLU-PMs-SS). The nanosystem was prepared by using DHA-dithiodipropionic acid-octadecylamine prodrug and D-α-Tocopherol polyethylene glycol 1000 succinate-arbutin conjugate. The resultant D@GLU-PMs-SS exhibited excellent stability under conditions of storage and physiological environment. D@GLU-PMs-SS could be activated by glutathione (GSH), leading to the dissociation of nanoparticles and subsequent release of free DHA. <em>In vitro</em> experiments revealed that the host erythrocyte uptake of glucose-functionalized nanoparticles was significantly enhanced <em>via</em> GLUT-mediated transport. Cellular experiments illustrated that D@GLU-PMs-SS effectively reduced GSH concentrations in <em>Plasmodium</em>. Furthermore, D@GLU-PMs-SS displayed remarkable efficacy in inhibiting the growth of <em>Plasmodium</em> while maintaining biosafety. Overall, this study developed a strategy to enhance the targeting of nanoparticles to improve their therapeutic efficacy against malaria, warranting further investigation in clinical trials.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100370"},"PeriodicalIF":6.4,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144766926","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":"Exploring the influence of the nanoporous structure of nickel-based superalloy membranes on emulsification performance","authors":"Daniel Jupke ,&nbsp;Janik Marius Lück ,&nbsp;Joachim Rösler ,&nbsp;Jan Henrik Finke ,&nbsp;Arno Kwade","doi":"10.1016/j.ijpx.2025.100369","DOIUrl":"10.1016/j.ijpx.2025.100369","url":null,"abstract":"<div><div>Nanoporous structures made from nickel-based superalloy are fairly new and not thoroughly studied membrane materials for premix membrane emulsification. They show a different kind of pore structure than other membranes typically used in this process with a network of elongated, interconnected pores (150–400 nm). Two different membrane structures, resulting from different creep strains, times and temperatures during production, were investigated for their performance in premix membrane emulsification. The membranes were used in a system with a fixed process pressure, varying specific energy input via pressure or number of emulsification cycles. Furthermore, membranes with different manufacturing parameters and thicknesses were used. Both membrane structures achieved monomodal droplet size distributions with median droplet sizes under 500 nm in one emulsification cycle. The results indicate that while all droplet sizes fall within a comparable range, the pore sizes still play a significant role, with finer pores resulting in smaller droplets but broader droplet size distribution that showed minimal further breakup after repeated passes. The larger, more irregular pores showed the ability to further breakup droplets with increasing emulsification cycles, broadening their distribution. The findings also suggest that a pressure increase activates smaller pores that seem to remain inactive for emulsification at lower pressures, facilitating more transport and droplets breakup. Results underscore the critical role of elongational flow at the membrane inlet in promoting droplet breakup. This study strengthens the theory that droplet breakup in premix membrane emulsification requires droplets to be stretched as they enter the membrane, then breakup either spontaneously by surface instabilities when remaining in this elongated state for a sufficient time or deterministically by mechanical stresses such as shear caused by a tortuous channel.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100369"},"PeriodicalIF":6.4,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724444","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 the appearance of the Magenstrasse depend on the amount of water consumed?","authors":"Linus Großmann ,&nbsp;Johanna Cyrus ,&nbsp;Stefan Senekowitsch ,&nbsp;Toni Wildgrube ,&nbsp;Theodora Tzakri ,&nbsp;Marie-Luise Kromrey ,&nbsp;Werner Weitschies ,&nbsp;Michael Grimm","doi":"10.1016/j.ijpx.2025.100365","DOIUrl":"10.1016/j.ijpx.2025.100365","url":null,"abstract":"<div><div>The <em>Magenstrasse</em> (stomach road) is a phenomenon describing the rapid evacuation of water drunken after a solid meal from the stomach. So far, its existence has been demonstrated for water volumes of 150 mL or more. The aim of this three-arm, randomised, cross-over, 12-subject study was to investigate whether the <em>Magenstrasse</em> is also present for smaller water volumes. For this purpose, gastric emptying of 50, 100 or 150 mL of water that was administered after a light meal was determined using MR imaging. With each dose of water, a fast-dissolving compression coated tablet containing caffeine and iron oxide as well as a hard capsule containing stable isotope labelled caffeine and medium-chain triglycerides were administered. This made it possible to determine the initial localization of the respective forms in the stomach on MR images as a function of the amount of water drunk, and also to determine the emptying rates of the two caffeine variants using saliva samples that were obtained in the study and quantified using LC-MS/MS. Gastric emptying of the ingested water was rapid and usually completed after approximately 20 min, regardless of the applied volume. In contrast to the consumed water, gastric emptying of natural caffeine and stable isotope labelled caffeine was delayed. The capsule usually floated on liquid and chyme, whereas the compression coated tablet was often embedded in chyme.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100365"},"PeriodicalIF":5.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714209","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":"Release mechanisms of PLGA microparticles prepared using a microfluidics device or a beaker","authors":"L.A. Lefol ,&nbsp;A. Sodano ,&nbsp;P. Bawuah ,&nbsp;J.A. Zeitler ,&nbsp;J. Verin ,&nbsp;F. Danede ,&nbsp;J.F. Willart ,&nbsp;J. Siepmann ,&nbsp;F. Siepmann","doi":"10.1016/j.ijpx.2025.100366","DOIUrl":"10.1016/j.ijpx.2025.100366","url":null,"abstract":"<div><div>The aim of this study was to better understand the release mechanisms of poly(lactic-<em>co</em>-glycolic acid) (PLGA) microparticles prepared via emulsification - solvent extraction/evaporation using a “classical beaker” vs. a “microfluidics device”. Ibuprofen-loaded microparticles were studied by optical microscopy, SEM, X-ray powder diffraction, X-ray μCT and drug release measurements from <em>single</em> microparticles in well agitated phosphate buffer pH 7.4 or agarose gel (mimicking living tissue). The use of a microfluidics device facilitated the preparation of microparticles with a less broad size distribution. However, in addition to the microparticle size, the inner system structure was found to be also of utmost importance for the resulting drug release kinetics in this case. Interestingly, even microparticles with <em>similar size, composition and inner &amp; outer structure</em> exhibited a <em>broad spectrum of individual drug release patterns</em>. This was true, irrespective of the type of preparation method and experimental release set-up, and could be explained as follows: The investigated microparticles were characterized by a continuous inner pore network and an initially smooth &amp; non-porous surface. Drug release set on as soon as: (i) the pore network got direct access to the release medium (e.g., due to a “weak point” in the PLGA surface layer), or (ii) substantial system swelling started (after a lag-time of several days). Importantly, <em>each</em> microparticle had its own, specific structure, which determined “<em>its way</em>” to release the drug. Furthermore, the experimental conditions were found to be of key importance: The presence of a surrounding agarose gel protected the microparticles from damage caused by convective fluid flow, and hindered microparticle swelling, thus, slowing down drug release.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100366"},"PeriodicalIF":6.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749162","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}