AAPS PharmSciTech最新文献

{"title":"Optimizing In Vitro Skin Permeation Studies to Obtain Meaningful Data in Topical and Transdermal Drug Delivery.","authors":"Rajesh Sreedharan Nair, Nashiru Billa, Andrew P Morris","doi":"10.1208/s12249-025-03143-2","DOIUrl":"10.1208/s12249-025-03143-2","url":null,"abstract":"<p><p>Drug delivery through the skin provides several advantages over other administration routes, including the avoidance of first-pass metabolism and gastrointestinal side effects, prolonged drug release, and significant improvement in patient compliance. It is imperative to study the in vitro behavior of drugs and formulations before proceeding to in vivo evaluations. As the ethical guidelines for scientific research evolve, there is an increasing emphasis on adopting alternative methods to reduce animal use. An in vitro permeation study (IVPT) estimates the rate and extent of drug permeation from a topical or transdermal delivery, determining its availability at the skin layers or into the systemic circulation. Vertical Franz diffusion cells are commonly employed for IVPT studies to evaluate the permeation of drugs across skin or other biorelevant membranes. This comprehensive review provides a clear understanding of the importance of optimizing in vitro experimental conditions to obtain reliable and reproducible data. We discuss various in vitro skin models, including excised human and animal skins, human skin equivalents (HSEs), synthetic membranes, and 3D-printed skin models. Additionally, a broad overview of setting up in vitro diffusion cells is provided. Emphasis is given on donor phase design, receptor medium selection, the importance of solubility and stability studies, sampling techniques, and analysis methods. Meticulous design and optimization of in vitro permeation experiments are crucial for generating reproducible data, which are essential for predicting the dermatokinetics of drugs and formulations.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":"147"},"PeriodicalIF":3.4,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172184","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":"Mitigating Shear Stress in Spray Drying for RNA-Loaded Lipid Nanoparticles through Process and Formulation Optimization.","authors":"Susana Farinha, Rute Mota, Carolina Lopes, Ricardo Velez, Mara G Freire, Ana Aguiar-Ricardo, Miguel Ângelo Rodrigues, Luís Marques, Joana S Cristóvão, Paulo Roque Lino","doi":"10.1208/s12249-025-03133-4","DOIUrl":"10.1208/s12249-025-03133-4","url":null,"abstract":"<p><p>Lipid nanoparticles (LNPs) have emerged as effective delivery systems for nucleic acid therapies, exemplified by the success of Moderna and Pfizer/BioNTech COVID-19 vaccines. However, these therapies still present significant shelf-life stability limitations, often requiring conservative cold chain storage conditions. Given the hurdles associated with cold chain supply, it is critical to overcome the stability challenges of these therapies. Drying technologies, such as spray drying (SD), can improve stability by removing water and preventing RNA hydrolysis and degradation. Nonetheless, shear and thermal stresses from SD can introduce additional risks to both the nucleic acid and the delivery system. Here, microfluidics was used to produce ribonucleic acid (RNA)-loaded LNPs with high encapsulation efficiency (> 95%), which were subsequently used to optimize the SD. A thorough process and formulation optimization was performed to maintain the LNPs' colloidal stability and nucleic acid encapsulation efficiency after spray drying. Poloxamer 188 (P188) proved crucial in protecting LNPs from shear stress possibly due to its ability to insert itself within lipid layers, allowing the maintenance of colloidal stability during SD. Additionally, SD was benchmarked against freeze drying (FD) as an alternative low shear drying technology. Overall, the study demonstrates the importance of optimizing the SD process to enhance nucleic acid-loaded LNPs' stability and delivery potential.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":"145"},"PeriodicalIF":3.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172182","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":"Microneedle Innovations in Oral Therapeutics: Transforming Protein and Peptide Delivery.","authors":"Kirthana Gopal, Syed Mahmood, Zarif Mohamed Sofian, Ayah R Hilles, Najihah Mohd Hashim","doi":"10.1208/s12249-025-03127-2","DOIUrl":"10.1208/s12249-025-03127-2","url":null,"abstract":"<p><p>Therapeutic proteins and peptides hold great potential in treating metabolic disorders, infectious diseases, and cancers; however, their oral administration remains challenging due to enzymatic degradation and poor intestinal permeability. To address these limitations, microneedles have emerged as a promising, minimally invasive delivery system to enhance oral bioavailability. This review explores the advantages of microneedles in overcoming physiological barriers to protein and peptide delivery, discussing various types, including solid, dissolvable, coated, hollow, and hydrogel-forming microneedles, in terms of their structural properties, mechanisms of action, and drug release kinetics. Additionally, we examine how microneedles enable controlled and efficient therapeutic protein and peptide release, improving bioavailability and efficacy. Recent research on microneedle applications for transdermal and oral delivery is summarized, alongside a detailed overview of mathematical modeling approaches used to optimize drug release. Microneedles show promise for administering protein and peptides such as vaccines, insulin, and other biologics via the oral route, addressing current limitations in biopharmaceutical delivery. Recent in vivo studies reinforce their feasibility and clinical relevance, demonstrating improved patient compliance and therapeutic outcomes. By offering a safe, effective, and patient-friendly solution, microneedle technology represents a transformative approach to drug delivery, paving the way for non-invasive and convenient therapeutic strategies for protein and peptide-based treatments.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":"146"},"PeriodicalIF":3.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172179","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":"Printabily of Pharmaceutical-Grade Polymers using Selective Laser Sintering with a CO2 Laser","authors":"Atabak Tabriz,&nbsp;Laura Andrade Junqueira,&nbsp;Siva Satyanarayana Kolipaka,&nbsp;Ho-Wah Hui,&nbsp;Nathan Boersen,&nbsp;Sandra Roberts,&nbsp;John Jones,&nbsp;Dennis Douroumis","doi":"10.1208/s12249-025-03141-4","DOIUrl":"10.1208/s12249-025-03141-4","url":null,"abstract":"<div><p>Selective laser sintering (SLS) has gained attention for pharmaceutical applications and the printing of solid oral dosage forms. The aim of this study was to evaluate the suitability of various pharmaceutical-grade polymers for tablet production using an SLS printer equipped with a CO₂ laser. Seven polymers, offering a range of release profiles such as immediate, controlled, and pH-dependent, were selected for investigation. Initially, the materials were characterized, revealing significant variations in their properties, including glass transition temperature, degradation temperature, mean particle size, and flowability. While some polymers exhibited ideal properties for printing, others were less suitable. By varying printing parameters such as the laser power, bed temperature, scanning speed, and powder feed rate, all powders were used for the reproducible fabrication of tablets. The physical properties of the tablets, including the hardness and friability, as well as their microstructure were affected by both the polymer grade and the laser intensity. The tablet physical characteristics varied according to the used polymer and thus hardness values ranged from 31 to 350 N, while friability varied across different formulations, with few tablets exhibiting values below 1%, others between 1–3%, and some exceeding 5%. Overall, this work demonstrated the suitability of using various pharmaceutical-grade polymers to produce tablets using SLS with a CO₂ laser.</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 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03141-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144117571","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 and In Vivo Appraisal of Glycerylmonostearate/chitosan Hybrid Nanocapsules As Peroral Delivery System of Simvastatin","authors":"Mohammed Elmowafy,&nbsp;Khaled Shalaby,&nbsp;Nabil K. Alruwaili,&nbsp;Omar Awad Alsaidan,&nbsp;Mohammed H. Elkomy,&nbsp;Mohamed A. Abdelgawad,&nbsp;Ehab M. Mostafa,&nbsp;Ayman Salama,&nbsp;Abdulsalam M. Kassem,&nbsp;Mohamed F. Ibrahim,&nbsp;Mahran Mohamed Abd El-Emam","doi":"10.1208/s12249-025-03135-2","DOIUrl":"10.1208/s12249-025-03135-2","url":null,"abstract":"<div><p>Simvastatin is one the most commonly used drugs for treatment of hypercholesterolemia but suffers from low bioavailability (about 5%) owing to poor aqueous solubility and extensive first pass metabolism. Glycerylmonostearate/chitosan hybrid olive oil cored nanocapsules were fabricated by a self-assembly method. Nine batches were successfully produced based on glycerylmonostearate/chitosan ratio and olive oil concentration. Selected formulation was and evaluated for oral bioavailability enhancement and pharmacodynamics. Glycerylmonostearate/chitosan ratio strongly influence the particle size and encapsulation of the formulations. Higher concentrations of olive oil produced larger particle size, heterogeneous distribution and higher encapsulation. Embedding of SIM in system matrix with existence in amorphous state was verified by DSC and FTIR tools. Selected formulation significantly enhanced SIM oral bioavailability with a 3.27-time higher in AUC when compared to SIM suspension. In addition, <i>in vivo</i> prolonged effect was verified by higher elimination half-life and mean residence time in plasma. Furthermore, pathological changes in liver and aorta associated with Poloxamer 704 injection have been mostly corrected. Serum lipid profile, liver function enzymes and oxidative stress were also restored. According to these results, glycerylmonostearate/chitosan hybrid olive oil cored nanocapsules proved to be a promising formulation strategy to significantly enhance SIM peroral bioavailability and therefore 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 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091113","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":"Tablet Color Changes Due to Light Irradiation and Titanium Dioxide: Color Change Prevention Using Plasticizers","authors":"Yuki Matsushima,&nbsp;Reo Kainuma,&nbsp;Hidemasa Katsumi,&nbsp;Akiko Tanaka,&nbsp;Tomoyuki Furubayashi,&nbsp;Toshiyasu Sakane","doi":"10.1208/s12249-025-03132-5","DOIUrl":"10.1208/s12249-025-03132-5","url":null,"abstract":"<div><p>The color and shape of the tablets manufactured by pharmaceutical companies were selected with branding and anti-counterfeiting measures in mind. Our previous report clarified that the discoloration of tablets by light exposure is due to the degradation of hydroxypropyl methylcellulose in the coating film and that the degradation reaction is triggered by TiO₂. In this study, we identified a pharmaceutical excipient that prevents light-induced discoloration of the coating film mediated by TiO₂. Among the excipients examined, triethyl citrate and glycerol triacetate, which are used as plasticizers, prevented color changes in the tablets. The prevention of color change was attributed to increased tensile strength rather than the coating film's glassy or rubbery state. In conclusion, the color change of tablets owing to photochemical reactions with TiO2 can be prevented by using excipients which can increase the strength of the coating film.</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 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091114","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":"Cyclodextrin-Based Inclusion Complexes Improve the In Vitro Solubility and Pharmacokinetics of Ivacaftor Following Oral Administration in Mice","authors":"David S. Nakhla,&nbsp;Youssef W. Naguib,&nbsp;Sanjib Saha,&nbsp;Dylan Gao,&nbsp;Nikesh Gupta,&nbsp;Walla Malkawi,&nbsp;Timothy M. Acri,&nbsp;Aliasger K. Salem","doi":"10.1208/s12249-025-03131-6","DOIUrl":"10.1208/s12249-025-03131-6","url":null,"abstract":"<div><p>Cystic fibrosis is a serious life-threatening hereditary disease that occurs due to a mutation in the cystic fibrosis transmembrane conductance regulator gene (<i>CFTR</i>). Ivacaftor (IVA) is a drug that targets the mutated CFTR protein. IVA is highly hydrophobic (log <i>P</i> = 5.6) with poor aqueous solubility (0.05 µg/mL) and is formulated as an amorphous solid dispersion tablet under the brand name Kalydeco^®. The recommended daily dose of Kalydeco^® is twice per day with a high fat meal to aid in IVA’s absorption. In this research, we studied the application of cyclodextrins (CDs) to improve the dissolution of IVA. Phase solubility studies between IVA and four different CDs (α-, β-, γ-, and hydroxypropyl-β-CD [HP-β-CD]) were conducted and a significant improvement in IVA’s aqueous solubility with HP-β-CD was observed. Solid state characterizations confirmed the formation of IVA/HP-β-CD inclusion complexes. <i>In vitro</i> dissolution studies were conducted at pH = 6.8 and showed improvement in IVA’s rate and extent of dissolution with IVA/HP-β-CD (1:2) complexes in comparison to uncomplexed IVA. <i>In vivo</i> pharmacokinetics in mice showed a 2-fold increase in area under the curve (AUC) after the oral administration of the IVA/HP-β-CD complex in comparison to Kalydeco tablets. In addition, HP-β-CD extended the release of IVA from the IVA/HP-β-CD complexes with a longer T_max of 7.05 h compared to 2.96 h with Kalydeco^® tablets. These results demonstrate that CD inclusion complexes of IVA using HP-β-CD can be a successful alternative approach to improving the solubility of IVA while extending its release.</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 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03131-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144073873","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":"Formulation and In-Vitro Testing of Nebulized Camostat Mesylate Loaded Nanoliposomes for the Treatment of SARS-CoV- 2 Infection","authors":"Rama Kashikar,&nbsp;Arun Kumar Kotha,&nbsp;Rakshya Shrestha,&nbsp;Rudragouda Channappanavar,&nbsp;Mahavir Bhupal Chougule","doi":"10.1208/s12249-025-03099-3","DOIUrl":"10.1208/s12249-025-03099-3","url":null,"abstract":"<div><p>COVID- 19, caused by the coronavirus SARS-CoV- 2, has arisen as a global health epidemic, claiming the lives of millions of people throughout the world. Combating the pandemic has involved developing and approving vaccines and antiviral products. Camostat Mesylate (Camo) is a TMPRSS2 inhibitor that inhibits virus-cell membrane fusion and, thereby, viral multiplication. Significant limitations of using oral Camo include the limited amount of Camo reaching the site of action, lungs, side effects due to distribution to all tissues, and enzymatic breakdown in the gut. This investigation aims to develop self-administrable and patient-compliant extended-release Camo-loaded pegylated nanoliposomes (Camo-pegNLs) for delivering Camo directly to the lungs, thereby enabling faster onset of action and overcoming limitations of oral Camo delivery. We developed the Camo-pegNLs were composed of 1,2-dipalmitoyl-sn-glycerol- 3-phosphocholine (DPPC), 1,2-dioleoyl-sn-glycerol- 3-phosphoethanolamine (DOPE-PEG, MW2000) and cholesterol using the ethanol injection technique and syringe pump. The NLs were characterized for their particle size, polydispersity index (PDI), and zeta potential using Malvern Zetasizer. The assay, unentrapped Camo using Vivaspin 500 ultrafilter (10 kDa) and in-vitro release were determined. The Camo content was analyzed using a validated HPLC method. The aerodynamic properties of Camo-pegNLs were determined using a Westech Andersen Cascade Impactor (ACI) at 28.3L/min and a pneumatic jet nebulizer. The antiviral effect of Camo-pegNLs was assessed in Vero cells expressing TMPRSS2 and infected with SARS-CoV- 2. Camo-pegNLs suspension showed size of 167.50 ± 0.90 nm, zeta potential of 0.48 ± 0.04 mV, and PDI of 0.07 ± 0.01. The quantity of entrapped Camo was found to be 44.86 ± 1.35%w/v, and the drug loading was 27.41 ± 0.04%w/w. The Camo-pegNL- 2 had an extended release of up to 24 h, MMAD of 4.295 ± 0.1 µm, GSD of 1.915 ± 0.064, and FPF of 42.01% ± 6.90. Camo-pegNLs showed a significant antiviral effect on Vero cells compared to no treatment group (<i>p</i> &lt; 0.01). An efficacious nebulized Camo-pegNLs suspension product was successfully developed for direct lung delivery to Camo-pegNLs to treat the SARS-CoV- 2 infection.</p><h3>Graphical Abstract</h3><p>SARS-CoV- 2</p>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03099-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144073856","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":"Development and Preclinical Testing of a Rapid, High-Volume, Auto-Injector for Subcutaneous Administration with Recombinant Human Hyaluronidase","authors":"Robert J. Connor,&nbsp;Tara Nekoroski,&nbsp;David W. Kang","doi":"10.1208/s12249-025-03116-5","DOIUrl":"10.1208/s12249-025-03116-5","url":null,"abstract":"<div><p>Handheld auto-injectors (AIs) provide a convenient method for subcutaneous (SC) administration of therapeutics in clinical settings or at home via a caregiver or self-administration. However, AIs have been limited to low volumes (&lt; 2 mL), partly due to hyaluronan (HA), a glycosaminoglycan that acts as a barrier to bulk fluid flow in the SC tissue. Recombinant human hyaluronidase PH20 (rHuPH20) is an enzyme that temporarily depolymerizes HA to facilitate the dispersion of SC-administered therapeutics and may enhance the use of AIs capable of delivering high volumes. These studies detail the development and preclinical testing of a novel high-volume AI (HVAI) that successfully delivered 10 mL of a representative macromolecule (immune globulin; Ig) co-administered with rHuPH20 in ≤ 30 s (s) in a miniature pig model. Testing of a surrogate AI informed the development of a novel, clinically-ready prototype HVAI. HVAI injections of Ig co-administered with 2,000 U/mL rHuPH20 improved injection site outcomes (back-leakage, bleb size, swelling, induration) and yielded up to 30% faster injection times compared with injections of Ig alone. In a mock clinical study that replicated clinical settings, the HVAI delivered 10 mL of Ig with 4,000 U/mL rHuPH20 with mean (± standard error of the mean) injection durations of 19.8 s (± 0.5) using a thin-wall 25-gauge (G) needle and 30.0 s (± 1.1) using a standard 25G needle. The data presented here demonstrate the feasibility of the prototype HVAI for rapid, high-volume administration of a concentrated biologic with rHuPH20, and will inform future clinical testing.</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 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03116-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144073870","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":"Development and Evaluation of Cyclosporine a Mixed Micelle Eye Drops for Enhanced Ocular Drug Delivery","authors":"Yue Hu,&nbsp;Jiong Wu,&nbsp;Xiaoyan Du,&nbsp;Yan Shen,&nbsp;Daquan Chen,&nbsp;Xiujuan Feng,&nbsp;Dilei Yan","doi":"10.1208/s12249-025-03129-0","DOIUrl":"10.1208/s12249-025-03129-0","url":null,"abstract":"<div><p>Ocular drug delivery is hindered by anatomical and physiological barriers that limit drug bioavailability. Among emerging solutions, mixed micelle systems offer promising potential for enhancing the efficacy of ocular formulations. This study investigates the development and evaluation of a novel cyclosporine A (CsA) micellar eye drop formulation using octylphenol polyethylene glycol ether 40 (OP-40), a surfactant with favorable ocular delivery properties, and polyoxyethylene hydrogenated castor oil 40 (RH-40), a non-ionic surfactant that can enhance the dispersion and stability of the system. OP-40 was optimized through a purification process, and a hybrid micelle system was developed by screening excipients and refining the formulation process. The critical micelle concentration (CMC), crystalline form of CsA, interactions between surfactants and excipients, and the influence of excipients on buffer capacity were systematically examined. The resulting eye drops demonstrated favorable physicochemical characteristics, including pH, osmolality, and stability under both accelerated conditions and long-term storage at room temperature. Furthermore, the formulation exhibited no ocular irritation in rabbit models, confirming its safety. In conclusion, OP-40-based CsA mixed micelle eye drops provide a promising strategy to overcome ocular drug delivery challenges, with significant potential to enhance bioavailability and therapeutic efficacy in ophthalmic 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 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144073872","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}