AAPS PharmSciTech最新文献

{"title":"Development of a Single Vial Mass Flow Rate Monitor to Assess Pharmaceutical Freeze Drying Heterogeneity","authors":"Tiffany Yu,&nbsp;Richard Marx,&nbsp;Michael Hinds,&nbsp;Nicholas Schott,&nbsp;Emily Gong,&nbsp;Seongkyu Yoon,&nbsp;William Kessler","doi":"10.1208/s12249-024-02961-0","DOIUrl":"10.1208/s12249-024-02961-0","url":null,"abstract":"<div><p>During pharmaceutical lyophilization processes, inter-vial drying heterogeneity remains a significant obstacle. Due to differences in heat and mass transfer based on vial position within the freeze drier, edge vials freeze differently, are typically warmer and dry faster than center vials. This vial position-dependent heterogeneity within the freeze dryer leads to tradeoffs during process development. During primary drying, process developers must be careful to avoid shelf temperatures that would result in overheating of edge vials causing the product sublimation interface temperature to rise above the critical (collapse) temperature. However, at lower shelf temperatures, center vials require longer to complete primary drying, risking collapse or melt-back due to incomplete drying. Both situations may result in poor product quality affecting drug stability, activity, and reconstitution times. We present a new approach for monitoring vial location-specific water vapor mass flow based on Tunable Diode Laser Absorption Spectroscopy (TDLAS). The single vial monitor enables measurement of the gas flow velocity, water vapor temperature, and gas concentration from the sublimating ice, enabling the calculation of the mass flow rate which can be used in combination with a heat and mass transfer model to determine vial heat transfer coefficients and product resistance to drying. These parameters can in turn be used for robust and rapid process development and control.</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":"25 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142447416","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":"Discriminative Power of the Flow through Cell Dissolution Tester in Predicting the In Vivo Performance of Pentoxifylline SR Product under Fed and Fasting Conditions","authors":"Nesrin F. Taha,&nbsp;Laila H. Emara","doi":"10.1208/s12249-024-02956-x","DOIUrl":"10.1208/s12249-024-02956-x","url":null,"abstract":"<div><p>This study explored, for the first time the role of different designs of the Flow-Through-Cell (FTC, USP IV) dissolution Tester in predicting the <i>in-vivo</i> performance of Pentoxifylline (PTX) sustained-release (SR) market product, under fed &amp; fasting conditions. Release studies of Trental^® SR 400 mg (Sanofi, Egypt), were carried-out in the FTC under different conditions, including: different volumes / compositions of release media, variable FTC flow patterns as well as applying open / closed loop configuration setups. Pharmacokinetic (PK) data, obtained from literature, were converted to <i>in-vivo</i> fraction-absorbed [F_A] using Wagner-Nelson (WN) method. A 1:1 IVIVC was investigated by comparing PTX fraction-dissolved [F_D] under different FTC release designs <i>versus</i> calculated [F_A]. Predicted PK parameters were evaluated, and compared with actual data, with estimation of prediction-error (PE%). The suggested FTC design; a closed-loop setup, with turbulent-flow pattern of the dissolution medium; provided the most acceptable PTX release according to USP labeled limits (USP 27). Also, results showed that PTX release was pronouncedly increased in a finite-volume of gradient-buffer system rather than water, which guarantee complete resemblance to GIT environment. This release design presented the most predictive IVIVC model with PTX <i>in-vivo</i> performance under fasting / fed states, with acceptable PE% values in terms of C_max and AUCs. A suggested FTC design is proposed as an alternative dissolution model in the official USP-monograph for PTX SR 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":"25 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-024-02956-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438713","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":"Effect of Fluid Paraffin on the Formulation Properties of Pressure Sensitive Adhesive Formulations Containing Diclofenac Sodium","authors":"Kaede Osanai,&nbsp;Shunsuke Aoki,&nbsp;Chihiro Otsuka,&nbsp;Hirotaka Watanabe,&nbsp;Haruhiko Hikichi,&nbsp;Takayuki Terukina,&nbsp;Hiromu Kondo","doi":"10.1208/s12249-024-02959-8","DOIUrl":"10.1208/s12249-024-02959-8","url":null,"abstract":"<div><p>Understanding the relationship between the release characteristics of the active ingredient in the tape formulation and the pharmaceutical characteristics of the adhesive layer can optimize therapeutic efficacy and improve patient adherence. This study aimed to clarify the effect of liquid paraffine (LP)/styrene–isoprene-styrene (SIS) triblock copolymer ratio on pressure-sensitive adhesive (PSA) formulation properties, such as adhesive properties and drug release, with a certain amount of diclofenac sodium (DFS) and tackifier. The effects of changes in PSA composition in DFS-containing tape formulations on adhesive and drug release properties were evaluated. The viscoelasticity results showed rigid gel-like behavior at low angular frequencies regardless of the LP/SIS ratio, and deformable gel-like behavior at high angular frequencies, with a maximum plasticizing effect of LP up to an LP/SIS ratio of 3.7. The peel adhesion test results showed that peel adhesion was not affected, but indicated a decreasing trend by increasing the LP/SIS ratio in the presence of DFS. Drug release test results showed that DFS release increased up to 24 h for LP/SIS ratios of up to 3.7, but decreased when the LP/SIS ratio was 6. The results of the drug permeation tests were similar to those of the drug release tests. In conclusion, it is possible to change the drug release properties by changing the amount of LP in the tape formulation; however, no definitive correlation was found between the adhesive and drug release 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":"25 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438712","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":"Moxifloxacin HCl -loaded Cellulose Acetate Butylate In Situ Forming Gel for Periodontitis Treatment","authors":"Warakon Thammasut,&nbsp;Catleya Rojviriya,&nbsp;Pornsit Chaiya,&nbsp;Thawatchai Phaechamud,&nbsp;Sucharat Limsitthichaikoon","doi":"10.1208/s12249-024-02960-1","DOIUrl":"10.1208/s12249-024-02960-1","url":null,"abstract":"<p>Periodontitis presents significant treatment challenges due to its complexity and potential complications. In response, an <i>in situ</i> forming gel (ISG) loaded with moxifloxacin HCl (Mx) and cellulose acetate butyrate (CAB) was developed for targeted periodontitis therapy. Mx-loaded 10–45% CAB-based ISGs were developed, and their physicochemical properties such as rheology, viscosity, contact angle, gel morphology and gel formation, interface interaction were investigated. Moreover, the formulation performance studies including drug release and kinetics, <i>in vitro</i> degradation, and antimicrobial activities were also evaluated. The Mx-loaded ISGs containing 25–45% CAB demonstrated rapid matrix formation in both macroscopic and microscopic examinations and presented plastic deformation matrix. Tracking with sodium fluorescein and Nile red fluorescence probes indicated delayed solvent movement owing to CAB matrix formation. Adequate CAB content sustained Mx release for one week, following Peppas-Sahlin model and indicating a predominantly Fickian diffusion mechanism. Higher CAB content likely contributed to a denser matrix structure, leading to a slower <i>in vitro</i> degradation rate. Synchrotron radiation X-ray tomographic and SEM imaging provided insights into the CAB matrix structure and porous network formation. These ISG formulations effectively inhibited <i>Staphylococcus aureus, Escherichia coli, Candida albicans,</i> and <i>Porphyromonas gingivalis</i>. The Mx-loaded 40% CAB-based ISG shows promise as a dosage form for treating periodontitis. Further clinical trials are necessary to ensure the safety of this new ISG formulation, despite existing safety data for other medicinal uses of CAB.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434736","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":"Surfactant-Assisted Wet Granulation-Based Matrix Tablets without Exceptional Additives: Prolonging Systemic Exposure of Model BCS Class II Ketoprofen","authors":"Rahat Shamim,&nbsp;Sana Shafique,&nbsp;Khalid Hussain,&nbsp;Nasir Abbas,&nbsp;Sana Ijaz,&nbsp;Nadeem Irfan Bukhari","doi":"10.1208/s12249-024-02966-9","DOIUrl":"10.1208/s12249-024-02966-9","url":null,"abstract":"<div><p>The present study was aimed to ameliorate the issue of solubility and thereby, bioavailability of ketoprofen, a BCS Class II drug. The sustained release matrix tablets (MT) were prepared using surfactant-assisted wet granulation (SAWG) with 1–5% of different surfactants. The tablet characteristics were within the compendial limits. The selected sustained release-compliant matrix tablet formulation containing granules prepared using 3% Soluplus® (MT2) released the drug by swelling-erosion. In human volunteers, MT2 attained the maximum plasma concentration (C_max) of 5.72µg /ml ± 0.30 h, time to C_max (T_max) of 5.56 ± 0.30 h and maintained the plasma concentration above its minimum effective concentration (MEC), 0.7 µg.ml⁻¹ till 24h. A control formulation, prepared from granules without surfactant (MT16), promptly attained C_max of 9.62 ± 0.76 µg/ml within 1h but rapidly declined to below MEC in 8h. Area under the curve from initial point to infinity (AUC_0-∞) of MT2 (78.65 ± 7.64 µg.h.ml⁻¹) was 2.29 folds higher than 34.39 ± 3.06 µg.h.ml⁻¹ of MT16. With decreased C_max, increased AUC_0-∞, delayed T_max and retained ketoprofen concentration above MEC for longer time, MT2 corresponded with the <i>in-vitro</i> sustained drug release characteristic. There is a likelihood of administration of once-a-day single dose of MT2 without plasma fluctuations, expected from two doses of MT16. SAWG helped developing a swellable-erodible sustained release matrix tablet formulation of ketoprofen with the desired biopharmaceutical and pharmacokinetics properties, merely by addition of Soluplus® in granules and without incorporation of any special ingredients or the major manipulation of the formulative ingredients in the formulation.</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":"25 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434737","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 Versatile High-through-put Oligonucleotide LC–MS Method to Accelerate Drug Discovery","authors":"Changhong Yun,&nbsp;Hyun Chong Woo,&nbsp;Ditte Lovatt,&nbsp;Craig A. Parish,&nbsp;Daniel S. Spellman,&nbsp;Honglue Shen","doi":"10.1208/s12249-024-02934-3","DOIUrl":"10.1208/s12249-024-02934-3","url":null,"abstract":"<div><p>Liquid chromatography-mass spectrometry (LC–MS) is an effective tool for high-throughput quantification of oligonucleotides that is crucial for understanding their biological roles and developing diagnostic tests. This paper presents a high-throughput LC–MS/MS method that may be versatilely applied for a wide range of oligonucleotides, making it a valuable tool for rapid screening and discovery. The method is demonstrated using an in-house synthesized MALAT-1 Antisense oligonucleotide (ASO) as a test case. Biological samples were purified using a reversed liquid–liquid extraction process automated by a liquid handling workstation and analyzed with ion-pairing LC–MS/MS. The assay was evaluated for sensitivity (LLOQ = 2 nM), specificity, precision, accuracy, recovery, matrix effect, and stability in rat cerebrospinal fluid (CSF) and plasma. Besides some existing considerations such as column selection, ion-pairing reagent, and sample purification, our work focused on the following four subtopics: 1) selecting the appropriate Multiple Reaction Monitoring (MRM) transition to maximize sensitivity for trace-level ASO in biological samples; 2) utilizing a generic risk-free internal standard (tenofovir) to avoid crosstalk interference from the oligo internal standard commonly utilized in the LC–MS assay; 3) automating the sample preparation process to increase precision and throughput; and 4) comparing liquid–liquid extraction (LLE) and solid-phase extraction (SPE) as sample purification methods in oligo method development. The study quantified the concentration of MALAT-1 ASO in rat CSF and plasma after intrathecal injection and used the difference between the two matrices to evaluate the injection technique. The results provide a solid foundation for further internal oligonucleotide discovery and development.</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":"25 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399046","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":"Material-Sparing Approach to Predict Tablet Capping Under Processing Compression Conditions Based on Mechanical and Molecular Properties Derived from Compaction Simulation and Crystal Structural Analysis","authors":"Pratap Basim,&nbsp;Harsh S. Shah,&nbsp;Robert Sedlock,&nbsp;Bhavin V. Parekh,&nbsp;Rutesh H. Dave","doi":"10.1208/s12249-024-02950-3","DOIUrl":"10.1208/s12249-024-02950-3","url":null,"abstract":"<div><p>Present study evaluates the usability of compaction simulation-based mechanical models as a material-sparing approach to predict tablet capping under processing compression conditions using Acetaminophen (APAP) and Ibuprofen (IBU). Measured mechanical properties were evaluated using principal component analysis (PCA) and principal component regression (PCR) models. PCR models were then utilized to predict the capping score (CS) from compression pressure (CP). APAP formulations displayed a quadratic correlation between CS and CP, with CS rank order following CP of 200MPa &lt; 300MPa &lt; 100MPa, indicating threshold compression pressure (TCP) limit between 200 and 300 MPa, resulting in higher CS at 300 than 200 MPa regardless of increased CP. IBU formulations displayed a linear correlation between CS and CP, with CS rank order following CP of 100MPa &lt; 200MPa &lt; 300MPa, indicating TCP limit between 100 and 200 MPa, resulting in higher CS at 200 and 300 than 100 MPa regardless of increased CP. Molecular models were developed as validation methods to predict capping from CP. Measured XRPD patterns of compressed tablets were linked with calculated Eatt and d-spacing of slip planes and analyzed using variable component least square methods to predict TCP triggering cleavage in slip planes and leading to capping. In APAP and IBU, TCP values were predicted at 245 and 175 MPa, meaning capped tablets above these TCP limits regardless of increased CP. A similar trend was observed in CS predictions from mechanical assessment, confirming that compaction simulation-based mechanical models can predict capping risk under desired compression conditions rapidly and accurately.</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":"25 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399047","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":"Remote Regulatory Assessments of Bioavailability/Bioequivalence Study Conduct by the Office of Study Integrity and Surveillance","authors":"Monica Javidnia,&nbsp;Hasan A. Irier,&nbsp;Sean Kassim,&nbsp;Seongeun Julia Cho","doi":"10.1208/s12249-024-02967-8","DOIUrl":"10.1208/s12249-024-02967-8","url":null,"abstract":"<div><p>The Office of Study Integrity and Surveillance (OSIS) in CDER in FDA coordinates and conducts inspections of sites conducting bioavailability and/or bioequivalence (BA/BE) studies supporting regulatory submissions. In response to travel restrictions during the SARS-CoV-2 (COVID-19) public health emergency, OSIS developed and began conducting remote assessments of BA/BE sites in 2020. This paper provides an overview of remote regulatory assessments (RRAs) and OSIS’s approach to RRAs, including procedures, experiences, and examples of findings during RRAs. In addition, as OSIS continues to utilize RRAs while resuming inspections, some areas for improvement are discussed.</p></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399048","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":"New Insight for Enhanced Topical Targeting of Caffeine for Effective Cellulite Treatment: In Vitro Characterization, Permeation Studies, and Histological Evaluation in Rats","authors":"Shahinaze A. Fouad,&nbsp;Taher A. Badr,&nbsp;Ahmed Abdelbary,&nbsp;Maha Fadel,&nbsp;Rehab Abdelmonem,&nbsp;Bhaskara R. Jasti,&nbsp;Mohamed El-Nabarawi","doi":"10.1208/s12249-024-02943-2","DOIUrl":"10.1208/s12249-024-02943-2","url":null,"abstract":"<p>Cellulite (CLT) is one of the commonly known lipodystrophy syndromes affecting post-adolescent women worldwide. It is topographically characterized by an orange-peel, dimpled skin appearance hence, it is an unacceptable cosmetic problem. CLT can be modulated by surgical procedures such as; liposuction and mesotherapy. But, these options are invasive, expensive and risky. For these reasons, topical CLT treatments are more preferred. Caffeine (CA), is a natural alkaloid that is well-known for its prominent anti-cellulite effects. However, its hydrophilicity hinders its cutaneous permeation. Therefore, in the present study CA was loaded into solid lipid nanoparticles (SLNs) by high shear homogenization/ultrasonication. CA-SLNs were prepared using Compritol® 888 ATO and stearic acid as solid lipids, and span 60 and brij™35, as lipid dispersion stabilizing agents. Formulation variables were adjusted to obtain entrapment efficiency (EE &gt; 75%), particle size (PS &lt; 350 nm), zeta potential (ZP &lt; −25 mV) and polydispersity index (PDI &lt; 0.5). CA-SLN-4 was selected and showed maximized EE (92.03 ± 0.16%), minimized PS (232.7 ± 1.90 nm), and optimum ZP (−25.15 ± 0.65 mV) and PDI values (0.24 ± 0.02). CA-SLN-4 showed superior CA release (99.44 ± 0.36%) compared to the rest CA-SLNs at 1 h. TEM analysis showed spherical, nanosized CA-SLN-4 vesicles. Con-LSM analysis showed successful CA-SLN-4 permeation transepidermally and <i>via</i> shunt diffusion. CA-SLN-4 incorporated into Noveon AA−1® hydrogel (CA-SLN-Ngel) showed accepted physical/rheological properties, and <i>in vitro</i> release profile. Histological studies showed that CA-SLN-Ngel significantly reduced mean subcutaneous fat tissue (SFT) thickness with 4.66 fold (<i>p</i> = 0.035) and 4.16 fold (<i>p</i> = 0.0001) compared to CA-gel, at 7th and 21st days, respectively. Also, significant mean SFT thickness reduction was observed compared to untreated group with 4.83 fold (<i>p</i> = 0.0005) and 3.83 fold (<i>p</i> = 0.0043), at 7th and 21st days, respectively. This study opened new avenue for CA skin delivery <i>via</i> advocating the importance of skin appendages. Hence, CA-SLN-Ngel could be a promising nanocosmeceutical gel for effective CLT treatment.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-024-02943-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387208","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":"Advancements in Colon-Targeted Drug Delivery: A Comprehensive Review on Recent Techniques with Emphasis on Hot-Melt Extrusion and 3D Printing Technologies","authors":"Nouf D. Alshammari,&nbsp;Rasha Elkanayati,&nbsp;Sateesh Kumar Vemula,&nbsp;Esraa Al Shawakri,&nbsp;Prateek Uttreja,&nbsp;Mashan Almutairi,&nbsp;Michael A. Repka","doi":"10.1208/s12249-024-02965-w","DOIUrl":"10.1208/s12249-024-02965-w","url":null,"abstract":"<div><p>This review investigates the progression and effectiveness of colon-targeted drug delivery systems, offering a comprehensive understanding of the colon's anatomy and physiological environment. Recognizing the distinctive features of the colon is crucial for successfully formulating oral dosage forms that precisely target specific areas in the gastrointestinal tract (GIT) while minimizing side effects through mitigating off-target sites. This understanding forms the basis for designing effective targeted drug delivery systems. The article extensively examines diverse approaches to formulating drugs for colonic targeting, highlighting key polymers and excipients in their production. Special emphasis is given to innovative approaches such as hot-melt extrusion (HME) and three-dimensional printing (3D-P), renowned for their accuracy in drug release kinetics and intricate dosage form geometry. However, challenges arise regarding material standardization and the complex network of regulatory clearances required to confirm safety and effectiveness. The review provides insights into each application’s advantages and potential challenges. Furthermore, it sheds light on the local diseases that necessitate colon targeting and the available marketed products, providing an overview of the current state of colon-targeted drug delivery systems. Additionally, the review emphasizes the importance of testing drugs in a controlled <i>in vitro</i> environment during the development phase. It also discusses the future directions for successful development in this field. By integrating knowledge across anatomy, formulation techniques, and assessment methodologies, this review is a valuable resource for researchers navigating the dynamic field of colonic drug 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":"25 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-024-02965-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387206","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}