AAPS PharmSciTech最新文献

{"title":"The Preparation and Physicochemical Characterization of a Triple Synergistic Nanoplatform Designed for Targeted Subcutaneous Delivery of Sitagliptin with Potential for β-Cell Preservation","authors":"Mo’tasem M. Alsmadi,&nbsp;Rana Obaidat","doi":"10.1208/s12249-026-03489-1","DOIUrl":"10.1208/s12249-026-03489-1","url":null,"abstract":"<div><p>Effective diabetes management necessitates innovative strategies that simultaneously stimulate β-cell growth and prevent apoptosis. While sitagliptin is an established therapeutic, its clinical utility is often hampered by suboptimal oral bioavailability and a lack of site-specific delivery. This research details the development and <i>in vitro</i> assessment of Sita-Ex-Cs-SeNPs, a subcutaneous nanocarrier composed of sitagliptin-loaded chitosan-selenium nanoparticles conjugated with exenatide. The platform is engineered to leverage GLP-1 receptor affinity for pancreatic targeting and utilize selenium’s intrinsic antioxidant properties to achieve therapeutic synergy. We employed the ionotropic gelation technique to encapsulate sitagliptin and integrate exenatide and selenium into a unified, stable delivery system. The resulting nanoparticles exhibited a spherical architecture with an average diameter of 314.1 nm and a zeta potential of + 18.7 mV. We achieved a high encapsulation efficiency of 98%. Analytical techniques (DSC and PXRD) confirmed that sitagliptin transitioned to an amorphous state, while FTIR validated successful peptide conjugation. Release kinetics followed the Weibull model, demonstrating a controlled biphasic profile (57% over 24 h) that significantly extends the therapeutic window compared to the free drug. <i>Sita-Ex-Cs-SeNPs</i> offer a promising, biocompatible approach for targeted diabetes intervention. Although <i>in vitro</i> results confirm stable sustained release, subsequent <i>in vivo</i> trials are essential to validate their efficacy in β-cell preservation.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing Non-oncologic Drugs via Targeted Nanocarriers for Cancer Therapy: Mechanisms, Synergistic Combinations, and Clinical Translation","authors":"Nur Aininie Yusoh,&nbsp;Afiq Azil,&nbsp;Ahlam Zaid Alkilani,&nbsp;Mohd Basyaruddin Abdul Rahman,&nbsp;Azren Aida Asmawi,&nbsp;Rosniza Razali,&nbsp;Fatmawati Adam,&nbsp;Nurul Akmarina Mohd Abdul Kamal","doi":"10.1208/s12249-026-03491-7","DOIUrl":"10.1208/s12249-026-03491-7","url":null,"abstract":"<div><p>The urgent need for innovative cancer therapies has driven increasing interest in repurposing drugs originally developed for non-oncological diseases. Several FDA-approved and clinically investigated agents, including mesalamine, celecoxib, gliclazide, metformin, itraconazole, and doxycycline, have shown anticancer potential through diverse mechanisms. However, despite their therapeutic potential, many of these drugs suffer from limited tumor selectivity, suboptimal bioavailability, and off-target toxicity when used in oncology. Nanocarrier-based delivery systems offer a promising strategy to address these limitations by improving drug solubility, enhancing tumor accumulation, and enabling more selective delivery to cancer cells and the tumor microenvironment. In this context, nanocarriers not only serve as delivery vehicles but also provide opportunities for controlled release, combination therapy, and stimulus-responsive treatment strategies. This review summarizes recent progress in repurposing non-oncologic drugs for cancer therapy with a particular focus on nanocarrier-enabled delivery approaches. We discuss the molecular mechanisms underlying the anticancer activity of repurposed drugs, as well as their targeting of tumor cells, the tumor microenvironment, and cancer stem cells. In addition, we highlight advances in integrating these agents into nanocarrier platforms for combination therapy, photodynamic therapy, dual-drug delivery, and stimuli-responsive systems. Finally, we address translational challenges, including regulatory and intellectual property considerations, and discuss future perspectives involving artificial intelligence and personalized medicine to accelerate clinical implementation.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148323724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Permeability Barriers By Strategic Selection of Thiol Containing Coformer for Novel Cocrystals of Metformin","authors":"Mangesh R. Bhalekar,&nbsp;Ashwini R. Madgulkar,&nbsp;Shweta J. Khiratkar","doi":"10.1208/s12249-026-03486-4","DOIUrl":"10.1208/s12249-026-03486-4","url":null,"abstract":"<div><p>Metformin, a BCS Class III drug, is limited by poor intestinal permeability despite high solubility, affecting its bioavailability. This study aimed to enhance Metformin’s permeability via cocrystallization with functional coformers. L-Cysteine was selected based on ΔpKa criteria and presence of thiol (-SH) group, known to interact with epithelial tight junctions and enhancepermeability. Cocrystals were prepared using solvent evaporation at various drug-to-coformer ratios. 1:2 Metformin–Cysteine cocrystal showed improved dissolution and strong hydrogen bonding interactions confirmed by DSC and FTIR, with PXRD indicating new crystalline phases. In vitro dissolution rates of Metformin and its cocrystals were similar; however, ex vivo experiments demonstrated a 5.9 -fold increase in permeability with the Metformin–Cysteine cocrystal. In vivo pharmacokinetic studies in Wistar rats revealed a Tmax of 1 h, Cmax of 17.64 µg/mL, and AUC0–∞ of 118.86 µg h/mL, significantly higher than pure Metformin. These findings indicate that cocrystallization with L-Cysteine effectively enhances Metformin’s permeability and bioavailability. The thiol group in cysteine likely modulates intestinal barrier function, facilitating absorption. This study highlights the potential of functional coformers in overcoming permeability challenges in BCS Class III drugs and supports further development of Metformin–Cysteine cocrystals as improved oral formulations.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148323831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plume Geometry Matters: Investigating the Contribution of Mass-Based Plume Geometry to Aerosol Delivery Efficiency in pMDIs","authors":"Daniel Moraga-Espinoza,&nbsp;Eli Eshaghian,&nbsp;Tania F. Bahamondez-Canas,&nbsp;Hugh D. C. Smyth","doi":"10.1208/s12249-026-03485-5","DOIUrl":"10.1208/s12249-026-03485-5","url":null,"abstract":"<div><p>To improve the performance of pressurized metered dose inhalers (pMDIs) a better mechanistic understanding of early deposition within the device and upper airways is needed to move toward more efficient inhalation therapies. The present work aimed to address the longstanding gap between plume geometry (PG) measurements and pulmonary drug delivery by evaluating PG with the Plume Induction Port Evaluator (PIPE), a mass-based method that characterizes plume angles under flow and within a restricted geometry. Three Rhodamine B solution pMDI formulations containing 2.49, 9.99, and 19.99% ethanol were evaluated at 5, 25, and 37 °C. PG was characterized by high-speed laser imaging (HSLI, 0 L/min) and by PIPE connected to a Next Generation Impactor (NGI, 30 L/min). Formulation vapor pressure, droplet size by laser diffraction, aerodynamic particle size by cascade impaction, early deposition, fine particle fraction (FPF), and respirable fraction (RF) were also determined. Deposition patterns within PIPE were log-normally distributed and consistently downward oriented, allowing calculation of mass median plume angle (MMPA) under flow. HSLI and MMPA showed opposite responses to formulation vapor pressure, where higher vapor pressure produced narrower optical PG but wider mass-based plume angles. A multivariable model incorporating MMPA, volume median diameter, formulation vapor pressure, and the MMPA × pressure interaction predicted RF with strong agreement (R² = 0.919). These results show that early deposition in pMDIs is not governed by particle size alone, but also by plume trajectory under inhalation flow.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148314926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eigenrate-Based Thermodynamic Decomposition of Competing Release Mechanisms in Polymeric Nano- and Microspheres: The MMIR-S Framework with Arrhenius Dual-Population Burst Kinetics and Log-Normal Polydispersity Averaging","authors":"Pitt Supaphol","doi":"10.1208/s12249-026-03474-8","DOIUrl":"10.1208/s12249-026-03474-8","url":null,"abstract":"<div><p>Simultaneous operation of Fickian diffusion, swelling-mediated relaxation, and polymer erosion in polymeric nano- and microspheres produces release profiles whose mechanistic origins cannot be resolved by empirical models without system-specific refitting. I present the Modified Multicomponent Interactive Release for Spheres (MMIR-S) framework, a thermodynamically self-consistent mechanistic model for homogeneously loaded spherical particles that determines mechanism-specific release weights from tabulated molecular descriptors, without fitting to release data. The theoretical core is Thermodynamic Eigenrate Decomposition (TED), in which each mechanism is assigned a commensurable first-order depletion rate: the diffusion eigenrate (π²<i>D</i>_eff,app/<i>R</i>²) from the dominant eigenvalue of Fick's second law in spherical coordinates; the swelling eigenrate governed by the Flory–Rehner criterion, closing when <i>χ</i>_PM &gt; 0.5; and the erosion rate accommodating surface, first-order, or bulk erosion kinetics. Normalizing these rates yields mechanism weights summing to unity, connected to Hansen solubility parameters, Flory–Huggins interaction parameters, and partition coefficients without empirical intermediaries. The burst release term distinguishes physically adsorbed drug, governed by a first-order desorption rate constant, from chemically adsorbed drug governed by an Arrhenius rate constant parameterized by binding free energy, producing a biexponential burst profile. A polydispersity correction integrates the release function over a log-normal size distribution via Gauss–Hermite quadrature. Validation against the six-compound, two-pH, multi-polymer dataset of Stiepel <i>et al</i>. [1] demonstrates TED weight distributions consistent with effective diffusivity trends recovered by regression and machine learning. The framework recovers the Higuchi, Hopfenberg, and first-order models as limiting cases, providing a foundation for <i>a priori</i> prediction of release profiles from molecular structure alone.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148281802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of the Minimum Number of Usable Time\u0000 Points in Bootstrapped Data Sets on (f_2)\u0000 Confidence Interval Using Bootstrap Methodology for the Comparison of Dissolution\u0000 Profiles","authors":"Zhengguo Xu,&nbsp;Marina Cuquerella-Gilabert,&nbsp;Javier Zarzoso-Foj,&nbsp;Matilde Merino-Sanjuan,&nbsp;Víctor Mangas-Sanjuan,&nbsp;Alfredo García-Arieta","doi":"10.1208/s12249-026-03492-6","DOIUrl":"10.1208/s12249-026-03492-6","url":null,"abstract":"<div><p>To use the conventional <span>(f_2)</span>\u0000 method to compare dissolution profiles, at least 3 time points should be included;\u0000 however, when the bootstrap <span>(f_2)</span>\u0000 method is applied, there are no clear criteria in regulatory guidelines in this\u0000 regard. The effects of applying the minimum number of time points on the accuracy,\u0000 precision, type I error (TIE), and statistical power have been investigated in the\u0000 current study. Four scenarios were simulated where the reference product (R)\u0000 dissolves at different rates. For each scenario, 17 population dissolution profiles\u0000 of the test product (T) were simulated with predefined target population\u0000 <span>(f_2)</span>\u0000 values with different variability and samples sizes. For each bootstrapped data set,\u0000 the expected <span>(f_2)</span>\u0000 was calculated twice to obtain the 90% (CI) by applying the requirement of at least\u0000 3 time points (TP3) or at least 1 time point (TP1). The whole process was repeated\u0000 10000 times to evaluate the statistical properties. Effects on TIE and statistical\u0000 power of TP1 and TP3 are similar for scenario B to D but different for A due to lack\u0000 of enough time points in the bootstrapped data set. For A, TP3 shows much higher\u0000 power than TP1, and TIE can be controlled at an acceptable level. It is recommended\u0000 to calculate the expected <span>(f_2)</span>\u0000 with at least 3 time points for each bootstrapped data set, and there should be\u0000 enough number of calculable expected <span>(f_2)</span>\u0000 from the bootstrapped samples to obtain 90% CI to control TIE. When the variability\u0000 is high, sample size should be increased to improve statistical power.</p></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03492-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149034600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Charge-Interaction-Mediated Adsorption of Human Growth Hormone on Polymeric Nanoparticles","authors":"Rajeshwar Motheram,&nbsp;Rijo John,&nbsp;Jasmin Monpara,&nbsp;Pardeep Gupta","doi":"10.1208/s12249-026-03478-4","DOIUrl":"10.1208/s12249-026-03478-4","url":null,"abstract":"<div><p>The adsorption behavior of recombinant human growth hormone (r-hGH) on cationic (PS⁺, amidine) and anionic (PS⁻, sulfate) polystyrene surfaces was investigated under varying solution pH conditions (surface charge), ionic strengths (0.0075 M and 0.075 M), and solvent dielectric constants to elucidate the adsorption mechanism governed by physicochemical interactions. In addition, desorption upon dilution was also examined. The studies utilized ¹²⁵I-labeled r-hGH and demonstrated that adsorption of r-hGH onto both PS⁺ and PS⁻ surfaces was influenced by solution conditions, ionic strength, and solvent dielectric constant. Marked electrostatic repulsion accompanied by decreased adsorption was observed on PS⁺ surfaces at pH 2.5 and on PS⁻ surfaces at pH 7.2. Adsorption was highest near the isoelectric point of r-hGH but decreased with increasing ionic strength. PS⁺ and PS⁻ surfaces showed significantly different adsorption profiles, resulting from the combined effects of hydrophobic and electrostatic interactions involving r-hGH, the change in r-hGH confirmation in solution, and the structural characteristics of the surface adsorbed protein. Studies were also carried out to assess the effect of the presence of proteins and surfactants at an ionic strength of 0.0075 M over a pH range of 2.5–7.2. Under conditions where both proteins inhibited adsorption, β-casein exhibited a greater inhibitory effect than BSA. Surfactants exhibited concentration dependent effects, with Tween 20 producing stronger inhibition than Pluronic F-68. Overall, these results demonstrate that r-hGH adsorption onto charged polystyrene surfaces is influenced by a complex interplay of charged interactions, hydrophobic effects, competitive adsorption, surfactant effects, and protein conformational stability.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148275619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Characterization of Amorphous PVP K30–Phosphatidylcholine Dispersions for the Fixed-Dose Co-Delivery of Hesperetin and Cannabidiol Prepared by Hot-Melt Extrusion","authors":"Kamil Wdowiak,&nbsp;Judyta Cielecka-Piontek","doi":"10.1208/s12249-026-03484-6","DOIUrl":"10.1208/s12249-026-03484-6","url":null,"abstract":"<div><p>Hesperetin and cannabidiol (CBD) are promising plant-derived bioactives whose oral performance is limited by poor aqueous solubility. To address the shared biopharmaceutical limitations of both compounds, amorphous PVP K30–phosphatidylcholine dispersions were prepared via hot-melt extrusion (HME). A Box–Behnken design (DoE) was applied to investigate the impact of (i) total API load (hesperetin:CBD mass ratio 1:1), (ii) phospholipid content in the carrier, and (iii) extrusion temperature on the solubility of both actives. The resulting extrudates were characterized by XRPD, DSC, and FT-IR/ATR. Solubility and dissolution profiles were evaluated in phosphate buffer (pH 6.8). <i>In vitro</i> passive permeability was assessed using PAMPA GIT model. DoE indicated that API load and phospholipid content were statistically significant factors for solubility of both hesperetin and CBD, whereas extrusion temperature was not significant within the studied range. XRPD confirmed amorphization for all formulations except F6, which contained a minor residual crystalline fraction of hesperetin. DSC revealed single glass-transition events, supporting good miscibility. The best-performing formulation (F7; 15% APIs, 20% phospholipid, 165°C) achieved solubilities of 4.934 mg/mL (hesperetin; 987-fold increase) and 4.314 mg/mL (CBD; 66,369-fold increase) and showed the highest permeability in PAMPA GIT model. HME-produced PVP K30–phosphatidylcholine amorphous dispersions substantially improved the solubility, dissolution behavior, and <i>in vitro</i> permeability of hesperetin and CBD, highlighting polymer–phospholipid amorphous dispersions as a promising solubility-enhancing platform for delivery of poorly soluble.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03484-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148275555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vitro Release Prediction of Colchicine Transdermal Patch Based on Raman Spectroscopy Imaging and Data-Driven Modeling","authors":"Xin Sha,&nbsp;Wenliang Dong,&nbsp;Lisong Zhang,&nbsp;Lian Li,&nbsp;Wenlong Li","doi":"10.1208/s12249-026-03480-w","DOIUrl":"10.1208/s12249-026-03480-w","url":null,"abstract":"<div><p>This study explored the feasibility of combining Raman spectroscopic imaging with data-driven modeling for estimating colchicine release from transdermal patches under <i>in vitro</i> conditions, aiming to reduce the operational complexity and long testing cycle of the conventional paddle-plate method. Ninety representative patch samples were prepared using a Box-Behnken design, with colchicine content, penetration enhancer content, and evaporation time as key variables. Surface Raman imaging data were collected, while reference release profiles were obtained by the paddle-plate method and fitted using the Weibull equation. Based on these data, three models-partial least squares regression, spectra-based convolutional neural network, and image-based convolutional neural network-were developed under curve-fitting-independent and curve-fitting-dependent strategies. Model performance was evaluated using R², root mean square error, and similarity factors <i>f</i>₁ and <i>f</i>₂. The curve-fitting-independent strategy showed better predictive performance than the curve-fitting-dependent strategy, and all three models met the commonly used similarity criteria (<i>f</i>₁ &lt; 15 and <i>f</i>₂ &gt; 50). The lower performance of the curve-fitting-dependent strategy was mainly related to scale differences among the release-equation parameters. Green analysis further indicated that the proposed method reduced solvent consumption, waste generation, and energy use compared with conventional testing. Overall, Raman spectroscopic imaging combined with data-driven modeling provides a non-destructive, greener, and relatively rapid approach for <i>in vitro</i> release prediction and quality evaluation of transdermal patches.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148269850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SeDeM-Guided Design and Optimization of MCC–Calcium Sulfate Co-Processed Excipient (MCCASUL) for Direct Compression Applications","authors":"Minal R. Narkhede,&nbsp;Sonal Y. Mhaske","doi":"10.1208/s12249-026-03479-3","DOIUrl":"10.1208/s12249-026-03479-3","url":null,"abstract":"<div><p>Direct compression is a generally preferred for tablet manufacturing method. However, it demands excipients with balanced flowability, compressibility, and packing properties. Microcrystalline cellulose (MCC) and calcium sulphate (CaSO₄) have balancing functionalities but individual limitations. To develop and optimize a novel MCC–CaSO₄ co-processed excipient (MCCASUL) for direct compression application using the SeDeM Expert System. To determine critical material attributes (CMA),12 SeDeM parameters were used to categorised MCC and CaSO₄. Functional indices, Parametric Profile Index (IPP), and Good Compression Index (IGC) were also calculated. To overcome the compressibility deficiency of CaSO₄ the required proportion of MCC was determined using SeDeM dilution potential equation. Co-dispersion method was used to prepare 9 MCCASUL batch with varying MCC:CaSO₄ ratios and further evaluated using SeDeM indices. Further characterization by FTIR, DSC, SEM, Heckel, and Kawakita analyses were performed for the optimised batch. MCC was more compressible (ѱc = 7.00) than CaSO₄ (ѱc = 4.67). The theoretical amount of correction for MCC was 14.16% among the batch preparation made, MCCASUL 4 exhibited the best results (IPP = 6.50, ѱf = 7.46, ѱc = 6.31). FTIR analysis proved the compatibility between the materials, DSC analysis revealed that modified thermal characteristics were stable, and SEM revealed improved morphology. With SeDeM expert System, co-processing yielded MCCASUL a highly versatile excipient that exhibited superior flowability, compressibility and stability and showed immense potential for direct compression tablet production.</p><h3>Graphical Abstract</h3><p>SeDeM-guided systematic development and optimization of MCCASUL coprocessed excipient demonstrating enhanced flowability, compressibility, and direct compression suitability.</p><div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}