AAPS PharmSciTech最新文献

{"title":"QbD-Based Development of Fluocinolone Nanocomposite Transdermal Gel: Optimization, Characterization, and Enhanced Anti-hyperpigmentation Efficacy Assessment","authors":"Priyanka Rathore,&nbsp;Rishikesh Gupta,&nbsp;Prem Prakash Singh,&nbsp;Anshu Awasthi,&nbsp;Ankita Kishore,&nbsp;Kuldeep K. Bansal,&nbsp;Alok Kumar Mahor","doi":"10.1208/s12249-025-03094-8","DOIUrl":"10.1208/s12249-025-03094-8","url":null,"abstract":"<div><p>The current study presents a comprehensive pharmaceutical engineering approach to developing an advanced transdermal drug delivery system for addressing skin hyperpigmentation through innovative nanocomposite gel formulation. Utilizing a systematic Quality-by-Design (QbD) methodology with Box-Behnken design, we developed a novel fluocinolone-loaded chitosan-graphene oxide nanocomposite (FCGN1) aimed at optimizing pharmaceutical performance and therapeutic efficacy. The nanocomposite formulation demonstrated critical pharmaceutical quality attributes: a precisely controlled nanoscale particle size of 144.78 ± 0.15 nm, stable zeta potential of -17.93 ± 3.75 mV, and high drug entrapment efficiency of 81.3 ± 3.64%. The optimized gel formulation (FNTG3) exhibited superior transdermal delivery characteristics, achieving approximately 70% permeation within 15 h and a significant flux rate of 190 µg/cm², which substantially outperforms current market alternatives. The comprehensive pharmaceutical evaluation included rigorous stability studies over 45 days, confirming consistent physical stability and sustained drug permeation. <i>In vivo</i> assessments using a UVB-induced hyperpigmentation rat model validated the formulation's dermal tolerability and depigmentation potential, demonstrating comparable or superior performance to commercial hydroquinone treatments. Histopathological analyses revealed pronounced depigmentation effects, attributable to the synergistic design of the nanocomposite system. The strategic integration of fluocinolone, chitosan, and graphene oxide facilitated enhanced drug release kinetics and improved skin penetration, highlighting the potential of rational pharmaceutical design in developing advanced topical delivery systems. This research provides a robust framework for developing sophisticated pharmaceutical dosage forms with enhanced therapeutic performance, offering significant insights into nanoscale drug delivery technologies for dermatological applications. The findings underscore the importance of systematic optimization and multifunctional component design in creating innovative pharmaceutical formulations.</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 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143761754","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":"Investigation of Curcumin-β-Cyclodextrin Complex Release in Injectable Hyaluronic Acid/Quince Seed Gum Hydrogel","authors":"Serdar Kolay,&nbsp;Nilhan Kayaman Apohan,&nbsp;Erdinç Babuç,&nbsp;Gökay Gün","doi":"10.1208/s12249-025-03095-7","DOIUrl":"10.1208/s12249-025-03095-7","url":null,"abstract":"<div><p>Injectable hydrogels play a crucial role in various biomedical applications, serving as fillers in tissue engineering, facilitating cell repair, and contributing to the development of drug delivery systems. This study aims to investigate the release of dissolved curcumin from a new injectable hyaluronic acid/quince seed gum (HA/QSG) hydrogel. Curcumin possesses numerous biological activities, including anti-cancer, antioxidant, antimicrobial, and anti-inflammatory properties. However, due to its very low water solubility, its bioavailability is poor. To address this, curcumin was encapsulated in three inclusion complexes: Cur 1:2 β-CD, Cur 1:4 β-CD, and Cur 1:6 β-CD. These Cur-β-CD inclusion complexes were lyophilized and converted into a water-soluble form. The curcumin, bisdemethoxycurcumin, and desmethoxycurcumin content of the obtained lyophilized Cur-β-CD complexes were analyzed using the HPLC method. HA-QSG hydrogels were loaded with Cur 1:2 β-CD inclusion complex in compositions of 0.75% (w/w), 0.50% (w/w), and 0.25% (w/w). The dissolution profiles of the HA-QSG hydrogels were examined in a pH 6.8 phosphate buffer medium, used as the swelling medium in intra-articular hydrogels. The initial burst of the 0.75% (w/w) hydrogel reached 9% release within the first 15 min, whereas the 0.25% (w/w) hydrogel exhibited only 6% release during the same period. The 0.75%(w/w) and 0.50% (w/w) hydrogels displayed very similar dissolution profiles, with a slightly faster release in the early stages of dissolutions, compared to the 0.25%(w/w) Cur β-CD-HA-QSG hydrogel. The 0.25%(w/w) Cur β-CD-HA-QSG hydrogel demonstrated a relatively slower release rate particularly during the initial stage of dissolution period. However, all three formulations reached approximately 98% release within 24 h. While the 0.75%(w/w) and 0.50%(w/w) curcumin-loaded HA-QSG hydrogels, with their rapid initial release, may be suited for intra-articular applications requiring quick drug availability, the 0.25%(w/w) curcumin-loaded HA-QSG hydrogel, with its slower release, may be more beneficial for sustained intra-articular delivery.</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 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03095-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749116","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":"Biogenic Amino Acid Cross-Linked Hyaluronic Acid Nanoparticles Containing Dexamethasone for the Treatment of Dry Eye Syndrome","authors":"Ajit Mishra,&nbsp;Jitu Halder,&nbsp;Ivy Saha,&nbsp;Vineet Kumar Rai,&nbsp;Ritu Mahanty,&nbsp;Deepak Pradhan,&nbsp;Priyanka Dash,&nbsp;Chandan Das,&nbsp;Tushar Kanti Rajwar,&nbsp;Bibhanwita Satpathy,&nbsp;Salim Manoharadas,&nbsp;Muralidhar Tata,&nbsp;Amit Goyal,&nbsp;Biswakanth Kar,&nbsp;Goutam Ghosh,&nbsp;Goutam Rath","doi":"10.1208/s12249-025-03090-y","DOIUrl":"10.1208/s12249-025-03090-y","url":null,"abstract":"<div><p>Ocular barriers, poor retention time, and frequent ocular discharge suppress the activity of Dexamethasone. Arginine (Arg) and hyaluronic acid (HA) are crucial for maintaining ocular health because of their unique biological benefits. In this study, we investigated the cationic properties of arginine to develop dexamethasone-loaded HA nanoparticles (ADHA NPs) and evaluated their therapeutic potential in alleviating dry eye syndrome using various reported <i>in-vitro</i> and <i>in-vivo</i> techniques. The ionic cross-linking method was used to prepare ADHA NPs. The ADHA NPs exhibited nearly 94.99 ± 4.16% drug release at the end of 6 h and followed the Korsemeyar-Peppas kinetic model (R² = 0.9811). Moreover, the developed formulation exhibited a higher water retention capacity, i.e., 86.89 ± 1.41%, and revealed enhanced mucoadhesion characteristics. ADHA NPs also exhibited significant anti-inflammatory effects (<i>p</i> &lt; 0.001) compared to dexamethasone in LPS-induced RAW 264.7 cell lines against proinflammatory cytokines IL-1 β, NO and TNF-α. Furthermore, cell line studies in HCECs (human corneal epithelial cells) showed cytocompatibility and a dose-dependent uptake of ADHA NPs. ADHA NPs also maintained the cell integrity against 0.005% benzalkonium chloride (BAC) induced dry eye model on HCECs. Further, the Schirmer tear test showed twofold enhanced tear production in the developed formulation, and ADHA NPs seem to maintain the uniform structure of the tear. <i>In vivo,</i> drug retention studies ensured the good retention properties of ADHA NPs up to 12 h. In conclusion, ADHA NPs, because of their anti-inflammatory, mucoadhesiveness, modified drug release capacity, and higher drug retention properties, could serve as a potential therapeutic alternative for treating dry eye conditions.</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 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717045","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":"Harnessing Exercise-Like Benefits of Protonation prone Liposomal Resveratrol in Differentiated Fat Cells: A Proof-of-Concept Study","authors":"Nupur Vasdev,&nbsp;Tanisha Gupta,&nbsp;Anoothi Bain,&nbsp;Dnyaneshwar Kalyane,&nbsp;Suryanarayana Polaka,&nbsp;Rakesh Kumar Tekade","doi":"10.1208/s12249-025-03085-9","DOIUrl":"10.1208/s12249-025-03085-9","url":null,"abstract":"<div><p>Obesity is a significant health issue resulting from a sedentary lifestyle and is linked to numerous other serious conditions, including cancer, diabetes, and cardiovascular diseases. Consequently, resveratrol (RES) is gaining attention as an emerging therapeutic agent due to its exercise-like effects. However, RES's instability and low aqueous solubility have limited its applications. This research report focuses on the loading, solubilization, and sustained delivery of RES using a dendrimer complex loaded liposomal formulation. The safety and efficacy of formulation was studied by performing various assays. The DEN-RES complex loaded liposomes were optimized using a Quality by Design (QbD) approach whereas particle size, PDI and zeta potential were found to be 159.29 ± 0.58 nm, 0.206 ± 0.008, and -7.2 ± 0.14 mV, which followed first-order release kinetics for sustained RES release. The mRNA levels of the SIRT1 and AMPK genes were found to be upregulated by more than two folds, whereas the LIPO-DEN-RES downregulated the mRNA expression of PPARγ in adipocytes. Therefore, the modulation of mRNA levels detected in 3T3-L1 cells post-treatment with the LIPO-DEN-RES validates the formulation's potential in addressing obesity.</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 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717044","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":"Exploration of Conventional and FDM-Mediated 3D Printed Tablets Fabricated Using HME-Based Filaments for pH-Dependent Drug Delivery","authors":"Ruchira Patil,&nbsp;Prajakta Bule,&nbsp;Naveen Chella","doi":"10.1208/s12249-025-03088-6","DOIUrl":"10.1208/s12249-025-03088-6","url":null,"abstract":"<div><p>Hot melt extrusion (HME) helps to improve the solubility of BCS class II and IV molecules. The downstream processing of the resulting filaments was crucial in developing the final dosage form. The present work investigates advantages of combining HME with fused deposition modelling (FDM) 3-Dimensional (3D) printing in delivering the naringenin to the colon to treat inflammatory bowel disease. HME filaments were made using a pH-sensitive polymer hydroxypropyl methylcellulose acetate succinate for the localized delivery of naringenin at the colonic pH. Polyethylene glycol (PEG – 4000) and Aerosil 200 were incorporated as plasticizer and flow modulator respectively, to facilitate the extrusion process. Naringenin was converted to amorphous form as confirmed by differential scanning calorimetry and powder x-ray diffraction. The optimized filament showed 0.03, 11.52 and 77.80% drug release at pH 1.2, 6.8 and 7.4 respectively. The tablets produced with the optimized filament by compression and 3D printing also confirmed the presence of naringenin in amorphous form and demonstrated pH-dependent release followed by zero-order release independent of the concentration. The dissolution profiles of FDM 3D printed (3DP) tablets with varying dimensions and infill densities suggested that both significantly influenced drug release from the tablets without altering the composition of tablets, indicating the potential application of 3D printing technology in developing personalized medicine according to patient requirements. These promising results may be valuable in evaluating the potential of naringenin in animal models, which may further facilitate clinical applications.</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 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717046","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":"Integrating Quantitative Methods & Modeling and Analytical Techniques in Reverse Engineering; A Cutting-Edge Strategy in Complex Generic Development","authors":"Akash Rajput,&nbsp;Megha Pillai,&nbsp;Jinal Ajabiya,&nbsp;Pinaki Sengupta","doi":"10.1208/s12249-025-03067-x","DOIUrl":"10.1208/s12249-025-03067-x","url":null,"abstract":"<div><p>Generic drugs are crucial for healthcare, offering affordable alternatives to brand-name drugs. Complex generics, with intricate ingredients, are gaining increasing importance in managing chronic conditions. However, prior to the regulatory market approval, they must demonstrate similarity in active ingredients, formulations, strength, and administration routes to ensure bioequivalence. The primary constraint lies in demonstrating bioequivalence with the innovator drug using traditional methods includes a lack of advanced technologies, and standardized protocols for analysing complex products. Given the multifaceted nature of these products, a single methodology may not suffice to establish <i>in vitro</i>/<i>in vivo</i> bioequivalence. Recognizing this, the USFDA conducts several workshops aiming advancement of complex generic drug product development. Notably, these efforts highlight the need to use Quantitative Methods and Modeling (QMM) approaches to support generic product development. QMM is a scientific approach used to analyze data and simulate drug development processes, ensuring safe, effective, and similar formulations of generic drugs using mathematical, statistical, and computational tools. QMM facilitates the design of formulations and processes, establishes a framework for <i>in vivo</i> BE studies, and suggests alternative ways to demonstrate BE. Appropriate utilization of the QMM approach can reduce the need for unwanted <i>in vivo</i> studies and bolster <i>in vitro</i> approaches for generic product development. Furthermore, use of orthogonal analytical techniques to characterize and decode innovator drugs can provide valuable insights into product attributes. Integrating this data into QMM enables the assessment of critical material attributes, or critical process parameters, thus demonstrating sameness. The combined application of QMM and analytical techniques not only supports regulatory decisions but also enhances the success rate of complex generic drug products.</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 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706929","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":"Co-Delivery of Tacrolimus and Thymoquinone Topically by Nanostructured Lipid Carrier Gel for Enhanced Efficacy Against Psoriasis","authors":"Meraj Alam,&nbsp;Md. Rizwanullah,&nbsp;Shahnawaz Ahmad,&nbsp;Ashif Iqubal,&nbsp;Showkat R. Mir,&nbsp;Tae-Geum Kim,&nbsp;Saima Amin","doi":"10.1208/s12249-025-03074-y","DOIUrl":"10.1208/s12249-025-03074-y","url":null,"abstract":"<div><p>Psoriasis is a chronic inflammatory skin disorder affecting 2–5% of the global population and is often characterized by skin thickening, scaling, and various epidermal changes. Current topical treatments have limitations in terms of efficacy, skin penetration, and side effects. The present study aimed to develop a novel nanostructured lipid carrier (NLC) gel that co-encapsulates tacrolimus (TAC) and thymoquinone (THQ) to enhance drug delivery and efficacy in the treatment of psoriasis. TAC-THQ-NLC was formulated using the emulsification solvent-evaporation technique and subsequently converted into nanogel using Carbopol Ultrez10 as a gelling agent. The prepared nanogel efficacy was evaluated through <i>ex-vivo</i> skin permeation, dermatokinetic analysis, and psoriasis-induced Balb/c mice model. The TAC-THQ-NLC-gel (TAC-THQ-NG) demonstrated significantly higher skin permeation compared to the TAC-THQ-suspension-gel (TAC-THQ-SG). Specifically, the permeation enhancement for the NLC-gel was 2.51-fold and 2.12-fold for TAC and THQ, respectively. These enhancements were confirmed using Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC). The dermatokinetic analysis showed that the TAC-THQ-NG had 2.78-fold and 2.37-fold higher maximum concentration (C_max) and 2.93-fold and 2.40-fold higher area under the curve (AUC) for TAC and THQ, respectively, compared to the TAC-THQ-SG. Further, in the Balb/c mice psoriasis model, the TAC-THQ-NG formulation resulted in an 83.80 ± 3.62% reduction in the cumulative Psoriasis Area Severity Index (PASI) score of thickness, erythema, and scaling, compared to the TAC-THQ-SG formulation, which showed 57 ± 9.90% reduction. The results of the <i>in vivo</i> skin compliance study suggested that the developed TAC-THQ-NG was safe for topical application. Further histopathological examination showed no significant changes in the skin, spleen, and liver, indicating the efficacy and safety of the TAC-THQ-NG formulation. Based on these observations, it can be inferred that the developed TAC-THQ-NG exhibits superior therapeutic efficacy.</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 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698686","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":"Treatment of Bleomycin-induced Pulmonary Fibrosis by Intratracheal Instillation Administration of Ellagic Acid-Loaded Chitosan Nanoparticles","authors":"Zhilin Luo,&nbsp;Yao Sun,&nbsp;Shihao Cai,&nbsp;Hongting Liu,&nbsp;Conglu Zhao,&nbsp;Xiang Xu,&nbsp;Aiguo Xu,&nbsp;Honggang Zhou,&nbsp;Cheng Yang,&nbsp;Xiaoting Gu,&nbsp;Xiaoyu Ai","doi":"10.1208/s12249-025-03086-8","DOIUrl":"10.1208/s12249-025-03086-8","url":null,"abstract":"<div><p>Idiopathic Pulmonary Fibrosis (IPF) is a rare and serious chronic interstitial lung disease that may endanger the lives of patients. The median survival time of patients with idiopathic pulmonary fibrosis is short, and the mortality rate is higher than that of many types of cancer. At present, pirfenidone (PFD) and nintedanib (NDNB) have been approved by FDA for IPF, but they can only delay the process of pulmonary fibrosis and cannot cure the disease. Therefore, it is urgent to develop other drugs with the effect of improving pulmonary fibrosis. Ellagic acid (EA) can inhibit the Wnt-signaling pathway and has an effect in treating pulmonary fibrosis induced by bleomycin (BLM) in mice. However, its solubility is poor, resulting in its low bioavailability and limited therapeutic benefits, so its clinical application has been limited. Herein, based on the characteristics of nano-drug lung delivery system, chitosan (CS) was selected as the carrier, and ellagic acid-loaded chitosan nanoparticles (EA-CS-NPs) were prepared by ionic gelation method. The EE% and DL% of prepared EA-CS-NPs was 73.73 ± 4.52% and 6.23 ± 1.09%, the particle size was 119.6 ± 5.51 nm (PDI = 0.234 ± 0.017), the zeta potential was 29.833 ± 0.503 mV. The morphology of the nanoparticles was observed by TEM microscope, which was round, uniform dispersion, indicating that the preparation process is stable and feasible. The toxicity experiment showed that EA-CS-NPs maintained 80% cell viability, significantly higher than that of the NDNB group, indicating lower toxicity and better inhibitory effects on TGF-β1-stimulated MLg and NIH-3T3 cells. Wound healing assay results showed that the inhibitory effect of EA-CS-NPs on cell migration was more pronounced than that of EA in the same amount of EA-containing drugs. Drug uptake experiments revealed that EA-CS-NPs significantly enhanced drug uptake in MLg and NIH-3T3 cells. <i>In vivo</i>, Cy7-CS-NPs exhibited higher fluorescence intensity in rat lungs compared to Cy7 solution, indicating better lung retention. The <i>in vivo</i> efficacy test showed that compared with the EA group, EA-CS-NPs could better reduce the area of pulmonary fibrosis and collagen deposition, improve lung function, and have a longer retention time in the lung. In summary, our results revealed that EA-CS-NPs may be a good choice for the treatment of pulmonary fibrosis.</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 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706926","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 Complex Generics and Similar Biological Products: An Industrial Perspective of Reverse Engineering","authors":"Rajeev Ranjan","doi":"10.1208/s12249-025-03087-7","DOIUrl":"10.1208/s12249-025-03087-7","url":null,"abstract":"<div><p>Generic drugs are developed to be bioequivalent to innovator formulation, matching them in dosage form, safety, strength, quality and efficacy. Known as \"interchangeable multi-source pharmaceutical products,\" generics play a crucial role in reducing therapeutic costs and enhancing patient compliance. Over the past decade, generics have accounted for more than 90% of prescriptions in the U.S., which has driven down the average price of these drugs to nearly match production costs once market competition grows. Simple generics of small-molecule drugs are often produced through trial and error based on existing data, but complex generics require advanced techniques like reverse engineering to replicate the brand drug's release profile. These complex generics include sophisticated drug delivery forms that ensure the therapeutic agent is released gradually, maximizing effectiveness. Conversely, similar biological products highly similar to approved biologics-undergo rigorous analytical and clinical evaluations due to their complexity and the nature of biologic production. The increased demand for similar biological products is driven by expiring biologic patents, economic incentives, and regulatory advancements, with the market expected to grow significantly by 2026. The Biologic Price Competition and Innovation Act (BPCIA) enable abbreviated approvals for similar biological products, promoting affordability. Despite minor differences from original biologics, similar biological products undergo extensive testing to ensure safety and efficacy, following global regulatory guidelines that emphasize strict quality standards. This framework is essential for expanding patient access to effective therapies for conditions like cancer and autoimmune diseases while supporting healthcare sustainability.</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 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706927","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":"Novel Methods Developed in Bioequivalence Assays: Patent Review","authors":"Brian Sebastian Correa Barrera,&nbsp;Izabel Almeida Alves,&nbsp;Diana Marcela Aragón","doi":"10.1208/s12249-025-03079-7","DOIUrl":"10.1208/s12249-025-03079-7","url":null,"abstract":"<div><p>This study examines advancements in bioequivalence (BE) assessment methods, with a focus on <i>in vitro</i>-<i>in vivo</i> correlation (IVIVC) and dissolution testing technologies. A systematic patent search was conducted via Espacenet, following PRISMA criteria and the study objectives, revealing 216 relevant patents, of which 28 were selected based on their contributions to novel BE methodologies. Analysis indicates a rapid increase in patent filings from 2021 to 2022, with a significant concentration of contributions from China. Key innovations include enhancements in dissolution testing apparatus, application of physiologically based pharmacokinetic (PBPK) modeling for IVIVC, and advanced statistical approaches for BE assessment. In dissolution testing, ƒ1 and ƒ2 factors remain essential metrics for assessing similarity, especially in solid oral dosage forms. These innovations enhance the efficiency (streamline) of BE evaluations, optimizing the biowaiver process and minimizing the need for extensive clinical trials while ensuring greater precision and reliability. The dissolution test, particularly when combined with PBPK models, allows for predictive evaluation of formulation changes and population-specific responses, fostering efficiency in drug development. Overall, these novel BE assessment approaches provide a framework for regulatory compliance, cost-effective production, and assurance of therapeutic equivalence in generic formulations. While they may not always be implemented in practice, they contribute significantly to innovation in the field, driving advancements in bioequivalence evaluation. This review highlights the evolving landscape of BE and IVIVC methodologies and underscores the importance of incorporating innovative testing approaches to advance pharmaceutical science and regulatory practices.</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 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698685","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}