AAPS PharmSciTech最新文献

{"title":"Optimization of Capecitabine-Loaded Niosomes Using Factorial Design: An Approach for Enhanced Drug Release and Cytotoxicity in Breast Cancer","authors":"Vidya Sabale,&nbsp;Ashwini Ingole,&nbsp;Rutuja Pathak,&nbsp;Prafulla Sabale","doi":"10.1208/s12249-025-03037-3","DOIUrl":"10.1208/s12249-025-03037-3","url":null,"abstract":"<div><p>Capecitabine, an oral prodrug of 5-fluorouracil, is increasingly being loaded into various drug delivery system to enhance its bioavailability and cytotoxicity. This study aimed to prepare and evaluate capecitabine-loaded niosomes as a drug delivery system for breast cancer treatment. The niosomes were prepared by thin film hydration method using Span 60 and cholesterol. Optimization was done using 3² factorial design with the responses of particle size and entrapment efficiency. Scanning electron microscopy (SEM) was used to observe the morphology. Fourier transform infrared spectroscopy (FTIR) and ultraviolet (UV) spectrophotometry were used to confirm the nature of the interactions. The optimized batch was further assessed for percent cumulative drug release, nature of crystallinity using the X-ray diffraction method, and drug excipient compatibility using FTIR and Differential Scanning Calorimetry (DSC). The optimized batch (F8) exhibited a particle size of 118 nm, a zeta potential of 24.1 mV, an entrapment efficiency of 93%, and a polydispersibility index (PDI) of 0.25. The cumulative drug release in a pH of 6.8 indicated that 86.46 ± 0.45% of the drug was released in 24 h. Cytotoxicity testing using MTT assay on MCF-7 breast cancer cell lines showed that the capecitabine niosomes were 2.6 times more cytotoxic than the pure drug. The study demonstrates that capecitabine-niosomes significantly enhanced the anticancer activity of capecitabine, suggesting a promising approach for breast cancer treatment.</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":"26 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143388832","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":"Unveiling the Potential of Nanosuspension Formulation Strategy for Improved Oral Bioavailability of Gefitinib","authors":"Parvez Sayyad,&nbsp;Shikha Jha,&nbsp;Reena Sharma,&nbsp;Vivek Yadav,&nbsp;Sanyog Jain","doi":"10.1208/s12249-025-03040-8","DOIUrl":"10.1208/s12249-025-03040-8","url":null,"abstract":"<div><p>Gefitinib (GB), an oral tyrosine kinase inhibitor suffers major setbacks in clinical application due to limited aqueous solubility leading to poor oral bioavailability. Nanosuspension serves as a promising formulation strategy to overcome the above-mentioned drawbacks. Hence, the present study involves the development of gefitinib nanosuspension (GB-NS) using High-pressure homogenization (HPH) to increase its aqueous solubility and maximize oral bioavailability. GB-NS was optimized by utilizing the quality-by-design strategy to optimize independent variables such as homogenization pressure, drug-to-stabilizer ratio, and number of cycles. Lecithin was found to stabilize the nanosuspension with optimal particle size, PDI, and zeta potential of 157 ± 18.77 nm, 0.296 ± 0.040, and -33.25 respectively. Intriguingly, a drug-to-stabilizer ratio significantly influenced (p &lt; 0.005) particle size and PDI, establishing its crucial role in optimization. The morphological characterization by SEM of GB-NS revealed a rod-shaped structure. Thereafter, the thermal and powder X-ray analysis depicted the crystalline nature of gefitinib in GB-NS. Additionally, GB-NS exhibited enhanced saturation solubility (~ 2.4- and ~ 3.4-fold) and dissolution rate (~ 2.5- and ~ 3.5-fold) compared to pure GB in 0.1 N HCl and PBS 6.8 respectively. GB-NS remained stable under both storage conditions ( 25°C and 4°C). Finally, the pharmacokinetic study depicted a considerable increase in C_max (~ 2.84-fold) and AUC_(0-t) (~ 3.87-fold) of GB-NS when compared to free GB. Therefore, developed formulations showed a competent solution for enhancing the oral bioavailability of poor water-soluble drugs.</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":"26 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143379834","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":"Experimental and Theoretical Investigation of the Formation of Daidzein Ion-pair Compounds: Solubility, Hydrogen Bonds, Stability","authors":"Zhaoyang Zhang,&nbsp;Sheng Wang,&nbsp;Qianlei Wang,&nbsp;Qian Ye,&nbsp;Wenjuan Wang","doi":"10.1208/s12249-025-03049-z","DOIUrl":"10.1208/s12249-025-03049-z","url":null,"abstract":"<div><p>Ion pairs represent a robust molecular force arising from the union of oppositely charged ions, held together by Coulomb attraction. Daidzein (Dai), categorized as a BCS IV drug, faces limitations in clinical application due to its relatively low solubility. To enhance the drug’s solubility, a Dai ion pair was prepared, and the mechanism underlying ion-pair formation was investigated. A comprehensive approach, combining experimental techniques and theoretical calculations, such as scanning electron microscopy, powder X-ray diffraction, differential scanning calorimetry, Fourier-transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, X-ray Photoelectron Spectroscopy, and computational simulation was employed to explore the ion-pair formation mechanism. The findings indicate a significant improvement in Dai solubility through the preparation of Arg and Lys ion-pair compounds. The results revealed that the Dai–Lys ion pair exhibited more short hydrogen bonds and fewer long hydrogen bonds than did the Dai–Arg ion pair, strengthening the intermolecular interactions and improving crystal structure stability. This study effectively enhanced the solubility of Dai and offers valuable insights into the mechanisms underlying ion pair formation in ionizable drugs.</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":"26 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143379835","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":"Current Status and Future Prospects of Lyotropic Liquid Crystals as a Nanocarrier Delivery System for the Treatment of Cancer","authors":"Raj Baldha,&nbsp;G. S. Chakraborthy,&nbsp;Sachin Rathod","doi":"10.1208/s12249-025-03058-y","DOIUrl":"10.1208/s12249-025-03058-y","url":null,"abstract":"<div><p>Multidrug resistance (MDR) poses a significant challenge in cancer treatment by reducing the efficacy of therapies. This review highlights the potential of lyotropic liquid crystals (LLCs) as innovative nanocarrier systems to overcome MDR. LLCs are characterized by their highly ordered internal structures, which can self-assemble into various phases, including lamellar, hexagonal, and cubic geometries. These structures allow LLCs to encapsulate and release cargo with diverse sizes and polarities, making them promising candidates for drug delivery applications. The phase of LLCs—whether cubic, hexagonal, or lamellar—can influence the physicochemical properties of encapsulated drugs, enabling tailored release profiles such as sustained, controlled, or targeted delivery. This review also explores the transitions in molecular geometry of amphiphilic compounds, additives, and hydrotrope molecules, which affect the formation and stability of LLC phases with varying pore sizes and water channels. The conclusion underscores the importance of ongoing research into LLCs for addressing cancer treatment challenges, including MDR. The versatility of LLCs extends beyond drug delivery to theranostic and diagnostic applications. By leveraging responsive smart drug delivery systems or incorporating natural compounds, LLCs offer a multifaceted approach to cancer therapy, highlighting their potential as a breakthrough in the field.</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":"26 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362069","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":"Current Developments in the Delivery of Gastro-Retentive Drugs","authors":"Kamal Shah,&nbsp;Disha Singh,&nbsp;Rutvi Agrawal,&nbsp;Akash Garg","doi":"10.1208/s12249-025-03052-4","DOIUrl":"10.1208/s12249-025-03052-4","url":null,"abstract":"<div><p>The pharmaceutical industry has expressed a lot of interest in site specific drug delivery &amp; oral controlled release to increase treatment efficiency. The idea of a unique drug delivery system was developed to address several concerns with the physicochemical characteristics of drug molecules and the associated formulations. The use of gastro retentive systems for drug delivery, which focus on site-specific drug release for either systemic or local effects in the stomach, is one of these cutting-edge strategies for lengthening gastric residency time. This approach is especially useful for drugs that have a small window of upper gastro intestinal tract absorption. This review has discussed various gastro-retentive techniques, including floating &amp; non-floating systems. With a focus on the numerous gastro retentive approaches that have lately emerged as the most efficient methods for site specific oral controlled release drug administration, the aim of this study on gastro retentive drug delivery systems was to synthesise the most current findings. We have highlighted the major reasons affecting gastric retention so that you may comprehend the many physiological challenges involved. Next, we discussed the different gastro retentive strategies that have been developed and improved to date, including floating, high density, mucoadhesive, unfoldable, expandable, super porous hydrogel, &amp; magnetic systems. The benefits of gastro retentive medication administration techniques were then thoroughly discussed.</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":"26 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362067","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":"Fabrication, Characterization, and Pharmacokinetics of Phospholipid-Based Naturosomal Nanocarriers for Enhanced Oral Solubility and Bioavailability of Naringin","authors":"Vijay Metkari,&nbsp;Rohit Shah,&nbsp;Nitin Salunkhe,&nbsp;Shailendra Gurav","doi":"10.1208/s12249-025-03047-1","DOIUrl":"10.1208/s12249-025-03047-1","url":null,"abstract":"<div><p>This study hypothesizes that phospholipid-based naturosoomal nanocarriers can significantly enhance the oral solubility and bioavailability of naringin (NARNs) by improving its absorption and pharmacokinetic profile. The NARNs were prepared using solvent evaporation techniques employing a quality-by-design approach followed by physicochemical (UV–visible spectroscopy, FTIR, DSC, XRD, SEM, TEM, PS, ZP analysis), functional (EE, apparent solubility, <i>in-vitro</i> drug release study) characterization and pharmacokinetic investigation. NARNs showed 91.15 ± 1.40% EE, with 12-fold aqueous solubility than the pure drug, i.e., naringin (NAR). The size of the NARNs vesicles was between 150 and 300 nm, demonstrating the controlled vesicle size, whereas the zeta potential and polydispersity index were -32.2 mV and 0.524, respectively signifying the excellent stability and homogeneity of naturosomal suspension. The NARNs <i>in-vitro</i> dissolution data demonstrated a superior release profile (92.12%) compared to pure NAR (38.90%) and physical mixture (43.72%). The pharmacokinetic parameters of NARN in the rabbit showed promising results (T_max = 2.0 h, C_max = 1.76 ± 0.10 µg/mL, and AUC_0-24 = 14.22 ± 0.13 µg/mL h). Thus, overall results indicated that naturosomal drug delivery is a capable method for improving the drug release profile of NAR and oral bioavailability, reducing toxicity by minimizing dose size.</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":"26 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03047-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143108180","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":"Investigating the Influence of Crospovidone’s Manufacturer Variability on Dissolution Profiles of Hydrochlorothiazide Tablets","authors":"Arash Yavari,&nbsp;Seyed Kazem Sadjady,&nbsp;Elham Moniri,&nbsp;Ali Nokhodchi,&nbsp;Fatemeh Haghighat Talab","doi":"10.1208/s12249-025-03039-1","DOIUrl":"10.1208/s12249-025-03039-1","url":null,"abstract":"<div><p>This study examines the influence of crospovidone (CP) manufacturer variability on the dissolution profiles of hydrochlorothiazide (HCTZ) tablets. Four CP batches from different manufacturers were characterized using pharmacopeial and physicochemical tests, including infrared absorption, loss on drying, and scanning electron microscopy (SEM). Significant differences were observed in the particle size distribution, wetting time, and water absorption capacities of the CP batches. Tablets were formulated using both direct compression and wet granulation methods. For the latter, the superdisintegrant was either added to the binder solution or incorporated intra- or extra-granularly. Disintegration and dissolution tests revealed that both CP concentration and the method of incorporation significantly affected tablet performance. Poly Kovidone and Max-Povidon exhibited superior performance at lower concentrations, while differences between brands became less pronounced at higher concentrations. The extra-granular method notably enhanced drug release profiles. Statistical analyses, including <i>f</i>_<i>2</i> similarity factors and MANOVA with Principal Component Analysis (PCA), highlighted significant differences in dissolution behavior among the formulations. These findings emphasize the importance of controlling excipient variability to ensure consistent product performance. The study concludes that a 2% CP concentration is optimal for mitigating source variability and that the extra-granular addition of CP in wet granulation is recommended for enhancing its functional properties.</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":"26 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143108183","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 of a Dermal Nanoemulsion with Antioxidants Derived from Rice Residues Using an HLD Theory Approach","authors":"Paola Vargas-Escobar,&nbsp;Patricia Quintero-Rincón,&nbsp;Oscar Flórez-Acosta","doi":"10.1208/s12249-025-03043-5","DOIUrl":"10.1208/s12249-025-03043-5","url":null,"abstract":"<div><p>Agricultural waste, such as rice straw, has become increasingly valuable as biocomposites in various industries. For cosmetic and pharmaceutical sectors, these biocomposites have improved active substance incorporation and waste reduction, which is pivotal for mitigating environmental impact. This study reports the encapsulation of a protein derivative derived from rice straw within a nanoemulsion for skin care applications, emphasizing stability and efficacy. Protein hydrolysates were produced by extracting proteins in an alkaline medium, followed by precipitation at the isoelectric point. The hydrolysates were enzymatically treated with Alcalase® at 80 °C and pH 10 for 45 min to generate antioxidant-rich formulations. Utilizing Hydrophilic-Lipophilic Deviation (HLD) theory, oil-in-water (O/W) emulsions were formulated by adjusting variables to achieve an HLD near zero. Sunflower oil and surfactants were combined, stirred at 70 °C, and homogenized using a rotor–stator. The final formulation's stability and permeability were evaluated through fluorescence microscopy, particle size analysis, zeta potential measurements, and accelerated stability assays. Nanoemulsion ENE37 showed high stability with 47.25 nm size, PDI 0.21, and excellent dispersion, maintaining integrity without phase separation. Hydrolyzed protein into ENE37 (NE37-HP) improved stability, increasing zeta potential and preventing aggregation while maintaining structure without phase inversion. NE37-HP exhibited shear-thinning behavior and good diffusion capacity, achieving 20.14 μg/cm².h. The HLD theory and ternary diagrams are valuable methodological tools for formulating stable nanoscale emulsions. Additionally, this dosage form, containing protein hydrolysates derived from rice straw, demonstrated potential for adequate dermal absorption in humans.</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":"26 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03043-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143108182","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":"Rodent Diets Incorporated with Live Biotherapeutic Products (LBPs): An Innovative Dosing Strategy to Support Preclinical Animal Studies on LBP Intervention","authors":"Haixi Cui,&nbsp;Yongrong Zhang,&nbsp;Hua Yu,&nbsp;R. Gary Hollenbeck,&nbsp;Lydia Nyasae,&nbsp;Yihan Wang,&nbsp;Yiguang Han,&nbsp;Zhiyong Yang,&nbsp;Hanping Feng,&nbsp;Stephen W. Hoag","doi":"10.1208/s12249-025-03050-6","DOIUrl":"10.1208/s12249-025-03050-6","url":null,"abstract":"<div><p>Currently, the administration of live biotherapeutic products (LBPs) in animal-based pre-clinical studies is achieved via oral gavage or voluntary consumption through the water supply. Oral gavage provides the most accurate and precise dosing for the administration of LBPs to laboratory animals; however, it induces stress responses and is labor-intensive, especially when long-term dosing is needed, placing a significant burden on both lab personnel and the subject animals. On the other hand, voluntary LBP consumption through water supply requires less effort and reduces animal stress, but still puts challenges concerning uncontrolled dosing, variations in LBP viability during the dosing period, uneven dosing due to sedimentation of LBPs, and the need for frequent refreshments due to stability and viability concerns in an aqueous environment. To address these problems, we developed lyophilized rodent diet pellets incorporated with stabilized Bioengineered Probiotic Yeast Medicines (BioPYM™), with customizable pellet size, robust mechanical strength, low friability, uniform BioPYM distribution, and proved stability for 10 weeks at 4 to 8°C storage, ensuring easy handling and more reliable dosing. Optimal cell viability preservation in dry diets was achieved through optimization of lyoprotectant and blending methods. Pharmacokinetic studies of the shedding of live BioPYM cells and their therapeutic payloads revealed the effective delivery of therapeutic agents targeting rodent gastrointestinal system. Overall, BioPYM-diet pellets represent an improved method for the delivery of LBP, and provide convenient and precise dosing. In addition, this method improves laboratory animal welfare and decreases laboratory workload.</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":"26 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03050-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143108181","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":"Evaluation of Physicochemical, Microstructure Parameters (Q3) and Performance Attributes of Commercial Ketoprofen Gels","authors":"Şeyma İşkin,&nbsp;Emine Kahraman,&nbsp;Sevgi Güngör","doi":"10.1208/s12249-025-03044-4","DOIUrl":"10.1208/s12249-025-03044-4","url":null,"abstract":"<div><p><i>In vitro</i> methods for quality and equivalence assessment of semi-solid products applied to the skin have increasingly garnered attention because <i>in vivo</i> bioequivalence studies is high cost, complexity, and time-consuming. Regulatory authorities established draft guidelines that outline a modular framework demanding qualitative, quantitative, microstructure and product performance equivalence to support generic products. In line with these guidelines, our study aimed to evaluate the relationship between microstructure and performance attributes in both originator and generic semi-solid products applied to the skin. In this context, reference and three generics of ketoprofen gel were selected as models for semi-solid formulations. Microstructure of all products was assessed regarding pH, specific gravity, drying rate, formulation rheology and potential drug polymorphism. Additionally, performance attributes of products were evaluated using <i>in vitro</i> release testing and <i>in vitro</i> permeation testing. Polymorphism and drying rate data showed no significant difference in microstructure of ketoprofen gels. All tested products exhibited <i>pseudo-plastic</i> flow behavior with <i>thixotropic</i> characteristic. However, differences in pH, specific gravity and viscosity values at low shear stress were observed between reference product and generic products, according to EMA guidance. Although IVRT outcomes did not entirely align with Q3 attributes, IVRT results for reference product <i>versus</i> Generic Product-I and Generic Product-II met the acceptance limits according to FDA guidance, which differs from EMA's assessment. Furthermore, <i>in vitro</i> release rate results were consistent with IVPT data. Consequently, it can be concluded that microstructure of semi-solid products applied to the skin may not consistently correlate with performance attributes due to various alternations influenced by manufacturing process parameters and/or formulation components.</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":"26 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03044-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143108225","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}