Pharmaceutical ResearchPub Date : 2024-08-01Epub Date: 2024-07-24DOI: 10.1007/s11095-024-03743-w
Showmika T Supti, Liam M Koehn, Stephanie A Newman, Yijun Pan, Joseph A Nicolazzo
{"title":"Iron Reduces the Trafficking of Fatty Acids from Human Immortalised Brain Microvascular Endothelial Cells Through Modulation of Fatty Acid Transport Protein 1 (FATP1/SLC27A1).","authors":"Showmika T Supti, Liam M Koehn, Stephanie A Newman, Yijun Pan, Joseph A Nicolazzo","doi":"10.1007/s11095-024-03743-w","DOIUrl":"10.1007/s11095-024-03743-w","url":null,"abstract":"<p><strong>Purpose: </strong>Alzheimer's disease (AD) is associated with brain accumulation of amyloid-beta (Aβ) and neurofibrillary tangle formation, in addition to reduced brain docosahexaenoic acid (DHA) and increased brain iron levels. DHA requires access across the blood-brain barrier (BBB) to enter the brain, and iron has been shown to affect the expression and function of a number of BBB transporters. Therefore, this study aimed to assess the effect of iron on the expression and function of fatty acid binding protein 5 (FABP5) and fatty acid transport protein 1 (FATP1), both which mediate brain endothelial cell trafficking of DHA.</p><p><strong>Methods: </strong>The mRNA and protein levels of FABP5 and FATP1 in human cerebral microvascular endothelial (hCMEC/D3) cells was assessed by RT-qPCR and Western blot, respectively following ferric ammonium citrate (FAC) treatment (up to 750 µM, 72 h). The function of FABP5 and FATP1 was assessed via uptake and efflux of radiolabelled <sup>3</sup>H-oleic acid and <sup>14</sup>C-DHA.</p><p><strong>Results: </strong>FAC (500 µM, 72 h) had no impact on the expression of FABP5 at the protein and mRNA level in hCMEC/D3 cells, which was associated with a lack of effect on the uptake of <sup>14</sup>C-DHA. FAC led to a 19.7% reduction in FATP1 protein abundance in hCMEC/D3 cells with no impact on mRNA levels, and this was associated with up to a 32.6% reduction in efflux of <sup>14</sup>C-DHA.</p><p><strong>Conclusions: </strong>These studies demonstrate a role of iron in down-regulating FATP1 protein abundance and function at the BBB, which may have implications on fatty acid access to the brain.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"1631-1648"},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11362236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pharmaceutical ResearchPub Date : 2024-08-01Epub Date: 2024-08-02DOI: 10.1007/s11095-024-03742-x
Albert Cao, Luchen Zhang, Yingzi Bu, Duxin Sun
{"title":"Machine Learning Prediction of On/Off Target-driven Clinical Adverse Events.","authors":"Albert Cao, Luchen Zhang, Yingzi Bu, Duxin Sun","doi":"10.1007/s11095-024-03742-x","DOIUrl":"10.1007/s11095-024-03742-x","url":null,"abstract":"<p><strong>Objective: </strong>Currently, 90% of clinical drug development fails, where 30% of these failures are due to clinical toxicity. The current extensive animal toxicity studies are not predictive of clinical adverse events (AEs) at clinical doses, while current computation models only consider very few factors with limited success in clinical toxicity prediction. We aimed to address these issues by developing a machine learning (ML) model to directly predict clinical AEs.</p><p><strong>Methods: </strong>Using a dataset with 759 FDA-approved drugs with known AEs, we first adapted the ConPLex ML model to predict IC <math><mmultiscripts><mrow></mrow> <mn>50</mn> <mrow></mrow></mmultiscripts> </math> values of these FDA-approved drugs against their on-target and off-target binding among 477 protein targets. Subsequently, we constructed a new ML model to predict clinical AEs using IC <math><mmultiscripts><mrow></mrow> <mn>50</mn> <mrow></mrow></mmultiscripts> </math> values of 759 drugs' primary on-target and off-target effects along with tissue-specific protein expression profiles.</p><p><strong>Results: </strong>The adapted ConPLex model predicted drug-target interactions for both on- and off-target effects, as shown by co-localization of the 6 small molecule kinase inhibitors with their respective kinases. The coupled ML models demonstrated good predictive capability of clinical AEs, with accuracy over 75%.</p><p><strong>Conclusions: </strong>Our approach provides a new insight into the mechanistic understanding of in vivo drug toxicity in relationship with drug on-/off-target interactions. The coupled ML models, once validated with larger datasets, may offer advantages to directly predict clinical AEs using in vitro/ex vivo and preclinical data, which will help to reduce drug development failure due to clinical toxicity.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"1649-1658"},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pharmaceutical ResearchPub Date : 2024-08-01Epub Date: 2024-08-06DOI: 10.1007/s11095-024-03737-8
Stephen R Byrn
{"title":"Accelerated Development of Pharmaceuticals Past, Present, and Future.","authors":"Stephen R Byrn","doi":"10.1007/s11095-024-03737-8","DOIUrl":"10.1007/s11095-024-03737-8","url":null,"abstract":"<p><p>This paper reviews the accelerated development of pharmaceuticals, exploring past, present, and future perspectives. It provides a historical overview of early strategies used to expedite development, beginning with initiatives from the 1990s. The work of Gardner and Byrn in accelerated development analysis during this era is highlighted. The narrative progresses to the 2000s, discussing the emergence of PK/PD in accelerating pharmaceutical development. The paper further examines case studies in the accelerated development field, including the INDIGO and Chorus programs. It concludes with an analysis of the current state of the field, referencing the NIPTE conference, which focused on the industrial perspective of accelerated development. Additionally, the paper outlines strategies for the rapid development of Solid Lipid Nanoparticle manufacturing and vaccine production.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"1547-1555"},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141898014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pharmaceutical ResearchPub Date : 2024-08-01Epub Date: 2024-08-06DOI: 10.1007/s11095-024-03756-5
Antonio Vitiello, Giovanni Rezza, Andrea Silenzi, Antonio Salzano, Mosè Alise, Maria Rosaria Boccellino, Annarita Ponzo, Andrea Zovi, Michela Sabbatucci
{"title":"Therapeutic Strategies to Combat Increasing Rates of Multidrug Resistant Pathogens.","authors":"Antonio Vitiello, Giovanni Rezza, Andrea Silenzi, Antonio Salzano, Mosè Alise, Maria Rosaria Boccellino, Annarita Ponzo, Andrea Zovi, Michela Sabbatucci","doi":"10.1007/s11095-024-03756-5","DOIUrl":"10.1007/s11095-024-03756-5","url":null,"abstract":"<p><p>The emergence of antimicrobic-resistant infectious pathogens and the consequent rising in the incidence and prevalence of demises caused by or associated to infections which are not sensitive to drug treatments is one of today's major global health challenges. Antimicrobial resistance (AMR) can bring to therapeutic failure, infection's persistence and risk of serious illness, in particular in vulnerable populations such as the elderly, patients with neoplastic diseases or the immunocompromised. It is assessed that AMR will induce until 10 million deaths per year by 2050, becoming the leading cause of disease-related deaths. The World Health Organisation (WHO) and the United Nations General Assembly urgently call for new measures to combat the phenomenon. Research and development of new antimicrobial agents has decreased due to market failure. However, promising results are coming from new alternative therapeutic strategies such as monoclonal antibodies, microbiome modulators, nanomaterial-based therapeutics, vaccines, and phages. This narrative review aimed to analyse the benefits and weaknesses of alternative therapeutic strategies to antibiotics which treat multidrug-resistant bacterial infections.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"1557-1571"},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141898017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pharmaceutical ResearchPub Date : 2024-08-01Epub Date: 2024-07-24DOI: 10.1007/s11095-024-03746-7
Mohammed Qusa, Hisham Qosa, Donna A Volpe
{"title":"Evaluation of In Vitro Metabolism- and Transporter-Based Drug Interactions with Sunscreen Active Ingredients.","authors":"Mohammed Qusa, Hisham Qosa, Donna A Volpe","doi":"10.1007/s11095-024-03746-7","DOIUrl":"10.1007/s11095-024-03746-7","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of this study was to examine the ability of sunscreen active ingredients to inhibit in vitro drug metabolism via cytochrome P450 (CYP) enzymes and drug uptake transporters.</p><p><strong>Methods: </strong>Metabolism assays with human liver microsomes were conducted for CYP2C9, CYP2D6 and CYP3A4 using probe substrates warfarin, bufuralol and midazolam, respectively. Uptake transporter assays with transfected cell lines were conducted for OAT3, OCT2 and OATP1B1 with probe substrates estrone-3-sulfate, metformin and rosuvastatin, respectively. Six sunscreen active ingredients, avobenzone, enzacamene, oxybenzone, octinoxate, trolamine, and homosalate, were evaluated up to their aqueous solubility limits in the assays.</p><p><strong>Results: </strong>None of the sunscreen active ingredients inhibited CYP2D6 or CYP3A4 activities in the microsomes at concentration ranges up to tenfold higher than their known clinical total plasma levels. Only enzacamene, oxybenzone and trolamine were found to be inhibitory to CYP2C9 activity with IC<sub>50</sub> values of 14.76, 22.46 and 154.7 µM, respectively. Avobenzone, enzacamene, homosalate and octinoxate were not inhibitory to the uptake transporters at the evaluated concentrations. Oxybenzone was inhibitory to OAT3 and OCT2 with IC<sub>50</sub> values of 39.93 and 42.77 µM, respectively. Trolamine also inhibited uptake in OAT3 and OCT2 transfected cells with IC<sub>50</sub> values of 448.1 and 1376 μM, respectively.</p><p><strong>Conclusions: </strong>Although enzacamene, oxybenzone and trolamine inhibited CYP2C9 and the renal transporters OAT3 and OCT2 in vitro, their IC<sub>50</sub> values exceeded total plasma levels found in clinical studies. Therefore, it is unlikely that these sunscreen active ingredients in sunscreen products will inhibit the metabolism or transport of co-administered drugs in consumers.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"1613-1620"},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fluorinated PAMAM-Arginine Carrier Prodrugs for pH-Sensitive Sustained Ibuprofen Delivery.","authors":"Carola Romani, Mattia Sponchioni, Alessandro Volonterio","doi":"10.1007/s11095-024-03747-6","DOIUrl":"10.1007/s11095-024-03747-6","url":null,"abstract":"<p><strong>Objective: </strong>The development of an efficient, multifunctional drug delivery system overcoming different obstacles generally associated with drug formulations, including the poor accumulation of the active principle in the target site and its sustained release for prolonged time.</p><p><strong>Methods: </strong>Our study proposes the development of a fluorinated poly(amidoamine) (PAMAM) carrier prodrug combining drug release boosted in alkaline environments with a possible implementation in <sup>19</sup>F MRI applications. In particular, we functionalized the terminal primary amines of PAMAM G2 and G4 through an ad hoc designed fluorinated ibuprofen-arginine Michael acceptor to obtain multifunctional ibuprofen-PAMAM-Arg conjugates.</p><p><strong>Results: </strong>These carriers demonstrated pH-dependent and sustained ibuprofen release for more than 5 days. This advantage was observed in both weak alkaline and physiological buffer solutions, allowing to overcome the limits associated to the burst release from similar fluorinated Arg-PAMAM dendrimers with ibuprofen physically encapsulated.</p><p><strong>Conclusion: </strong>These findings, coupled to the high biocompatibility of the system, suggest a potential synergistic biomedical application of our conjugates, serving as vehicles for drug delivery and as <sup>19</sup>F magnetic resonance imaging contrast agents.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"1725-1736"},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11362194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pharmaceutical ResearchPub Date : 2024-08-01Epub Date: 2024-07-13DOI: 10.1007/s11095-024-03729-8
M J Giménez, L Aguilar, L Alou, D Sevillano
{"title":"Comment on the article: In vivo Pharmacokinetics/Pharmacodynamics Profiles for Appropriate Doses of Cefditoren pivoxil against S. pneumoniae in Murine Lung-Infection Model.","authors":"M J Giménez, L Aguilar, L Alou, D Sevillano","doi":"10.1007/s11095-024-03729-8","DOIUrl":"10.1007/s11095-024-03729-8","url":null,"abstract":"","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"1595-1597"},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141601256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pharmaceutical ResearchPub Date : 2024-08-01Epub Date: 2024-08-07DOI: 10.1007/s11095-024-03740-z
Mohammad A M Momin, Dale Farkas, Michael Hindle, Felicia Hall, Robert M DiBlasi, Worth Longest
{"title":"Development of a New Dry Powder Aerosol Synthetic Lung Surfactant Product for Neonatal Respiratory Distress Syndrome (RDS) - Part I: In Vitro Testing and Characterization.","authors":"Mohammad A M Momin, Dale Farkas, Michael Hindle, Felicia Hall, Robert M DiBlasi, Worth Longest","doi":"10.1007/s11095-024-03740-z","DOIUrl":"10.1007/s11095-024-03740-z","url":null,"abstract":"<p><strong>Purpose: </strong>Improving the deep lung delivery of aerosol surfactant therapy (AST) with a dry powder formulation may enable significant reductions in dose while providing improved efficacy. The objective of Part I of this two-part study was to present the development of a new dry powder aerosol synthetic lung surfactant (SLS) product and to characterize performance based on aerosol formation and realistic in vitro airway testing leading to aerosol delivery recommendations for subsequent in vivo animal model experiments.</p><p><strong>Methods: </strong>A new micrometer-sized SLS excipient enhanced growth (EEG) dry powder formulation was produced via spray drying and aerosolized using a positive-pressure air-jet dry powder inhaler (DPI) intended for aerosol delivery directly to intubated infants with respiratory distress syndrome (RDS) or infant-size test animals.</p><p><strong>Results: </strong>The best-case design (D2) of the air-jet DPI was capable of high emitted dose (> 80% of loaded) and formed a < 2 µm mass median aerodynamic diameter (MMAD) aerosol, but was limited to ≤ 20 mg mass loadings. Testing with a realistic in vitro rabbit model indicated that over half of the loaded dose could penetrate into the lower lung regions. Using the characterization data, a dose delivery protocol was designed in which a 60 mg total loaded dose would be administered and deliver an approximate lung dose of 14.7-17.7 mg phospholipids/kg with a total aerosol delivery period < 5 min.</p><p><strong>Conclusions: </strong>A high-efficiency aerosol SLS product was designed and tested that may enable an order of magnitude reduction in administered phospholipid dose, and provide rapid aerosol administration to infants with RDS.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"1703-1723"},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11362531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pharmaceutical ResearchPub Date : 2024-08-01Epub Date: 2024-07-24DOI: 10.1007/s11095-024-03741-y
Mohhammad Ramzan, Afzal Hussain, Tasneem Khan, Mohd Usman Mohd Siddique, Musarrat Husain Warsi
{"title":"Tolterodine Tartrate Loaded Cationic Elastic Liposomes for Transdermal Delivery: In Vitro, Ex Vivo, and In Vivo Evaluations.","authors":"Mohhammad Ramzan, Afzal Hussain, Tasneem Khan, Mohd Usman Mohd Siddique, Musarrat Husain Warsi","doi":"10.1007/s11095-024-03741-y","DOIUrl":"10.1007/s11095-024-03741-y","url":null,"abstract":"<p><strong>Objective: </strong>Tolterodine tartrate (TOTA) is a first-line therapy to treat overactive urinary bladder (OAB). Oral delivery causes high hepatic clearance, xerostomia, headache, constipation, and blurred vision. We addressed Hansen solubility parameter (HSP) and Design Expert oriented optimized cationic elastic liposomes for transdermal application.</p><p><strong>Methods: </strong>The experimental solubility was conducted in HSPiP predicted excipients to tailor formulations using surfactants, stearylamine, ethanol, and phosphatidylcholine (PC). These were evaluated for formulation characteristics. The optimized OTEL1 and OTEL1-G (gel) were compared against the drug solution (DS) and liposomes. In vitro and ex vivo studies were accomplished to investigate the insights into the mechanistic understanding of TOTA release and permeation ability. Finally, confocal laser scanning microscopy (CLSM) supported ex vivo results.</p><p><strong>Results: </strong>HSP values of TOTA were closely related to tween-80, stearylamine, and human's skin. The size (153 nm), %EE (87.6%), and PDI (0.25) values of OTEL1 were in good agreement to the predicted values (161 nm, 80.4%, and 0.31) with high desirability (0.963). Spherical and smooth OTEL1 (including OTEL1-G and liposomes) vesicles followed non-Fickian drug release as compared to DS (Fickian) as evidence with n > 0.5 (Korsmeyer and Peppas coefficient). OTEL1 (containing lipid and surfactant as 90 mg and 13.8 mg, respectively) exhibited 2.6 and 1.8-folds higher permeation flux than DS and liposomes, respectively. Biocompatible cationic OTEL1 was safe and non-hemolytic.</p><p><strong>Conclusions: </strong>OTEL1 was promised as a lead vesicular approach and an alternative to conventional oral therapy to treat OAB in children and advanced age patients.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"1683-1702"},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pharmaceutical ResearchPub Date : 2024-08-01Epub Date: 2024-07-29DOI: 10.1007/s11095-024-03751-w
Shuai Bai Palmkron, Björn Bergenståhl, Stephen Hall, Sebastian Håkansson, Marie Wahlgren, Emanuel Larsson, Anna Millqvist Fureby
{"title":"The Impact of Annealing Methods on the Encapsulating Structure and Storage-Stability of Freeze-Dried Pellets of Probiotic Bacteria.","authors":"Shuai Bai Palmkron, Björn Bergenståhl, Stephen Hall, Sebastian Håkansson, Marie Wahlgren, Emanuel Larsson, Anna Millqvist Fureby","doi":"10.1007/s11095-024-03751-w","DOIUrl":"10.1007/s11095-024-03751-w","url":null,"abstract":"<p><strong>Objective: </strong>This paper investigates the critical role of material thickness in freeze-dried pellets for enhancing the storage stability of encapsulated bacteria. Freeze dried material of varying thicknesses obtained from different annealing durations is quantified using Scanning Electron Microscopy (SEM) and X-ray microtomography (μCT), the material thickness is then correlated to the storage stability of the encapsulated cells.</p><p><strong>Methods: </strong>A formulation comprising of sucrose, maltodextrin, and probiotic cells is quenched in liquid nitrogen to form pellets. The pellets undergo different durations of annealing before undergoing freeze-drying. The material thickness is quantified using SEM and μCT. Storage stability in both oxygen-rich and oxygen-poor environments is evaluated by measuring CFU counts and correlated with the pellet structure.</p><p><strong>Results: </strong>The varying annealing protocols produce a range of material thicknesses, with more extensive annealing resulting in thicker materials. Storage stability exhibits a positive correlation with material thickness, indicating improved stability with thicker materials. Non-annealed pellets exhibit structural irregularities and inconsistent storage stability, highlighting the impracticality of avoiding annealing in the freeze-drying process.</p><p><strong>Conclusions: </strong>Extensive annealing not only enhances the storage stability of probiotic products but also provides greater control over the freeze-drying process, ensuring homogeneous and reproducible products. This study underscores the importance of material thickness in freeze-dried pellets for optimizing storage stability for probiotic formulations, and emphasize the necessity of annealing as a critical step in freeze-drying quenched pellets to achieve desired structural and stability outcomes.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"1671-1682"},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11362187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}