Pharmaceutical Research最新文献

{"title":"Fabrication of Uniform Melatonin Microparticles Potentially for Nasal Delivery: A Comparison of Spray Drying and Spray Freeze Drying.","authors":"Chengzhi You, Shen Yan, Mengyuan Li, Shuaiyu Xie, Shengyu Zhang, Xiao Dong Chen, Winston Duo Wu","doi":"10.1007/s11095-024-03770-7","DOIUrl":"10.1007/s11095-024-03770-7","url":null,"abstract":"<p><strong>Purpose: </strong>Insomnia is a major health concern, and melatonin (MLT) is key for initiating sleep. Delivering MLT nasally can enhance brain bioavailability by targeting the olfactory region. This study aimed to fabricate MLT embedded microparticles for nasal delivery.</p><p><strong>Methods: </strong>MLT-cyclodextrin (CD) derivatives complex microparticles (MCCMPs) were fabricated by spray drying and spray freeze drying MLT and CD derivative solutions. Phase solubility and ¹H-¹H ROSEY NMR analysis assessed MLT-CD assembly. The effects of formulation compositions and process parameters on microparticle structural attributes were investigated. The in vitro nasal release and deposition performances were evaluated by a modified paddle-over-disk apparatus and 3D-printed nasal cavity cast, respectively.</p><p><strong>Results: </strong>Sodium sulphobutylether-β-cyclodextrin (SBE-β-CD) exhibited the best complexation ability with MLT, with the indole structure of MLT included in its cavity. Spray dried MCCMPs showed dense structure with high density, while the spray freeze dried counterpart showed the brittle and porous structure with low density. Despite the porous structure may promote the release rate of spray freeze dried samples, the high hydrophilicity of the CD derivative overshadows this advantage. Samples prepared by spray drying not only exhibited rapid release rates but also could deposit more effectively in the olfactory region, as they avoid breakage due to their higher mechanical strength. The optimal sample showed ~ 86.70% of the MLT released at 20 min and ~ 10.57% of the deposition fraction in the olfactory region.</p><p><strong>Conclusions: </strong>This work compares MCCMPs fabricated by spray drying and spray freeze drying, providing the optimal formulation and process combinations.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"2057-2073"},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406699","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":"Microstructural Characterization of Dry Powder Inhaler Formulations Using Orthogonal Analytical Techniques.","authors":"Gonçalo Farias, William J Ganley, Robert Price, Denise S Conti, Sharad Mangal, Elizabeth Bielski, Bryan Newman, Jagdeep Shur","doi":"10.1007/s11095-024-03776-1","DOIUrl":"10.1007/s11095-024-03776-1","url":null,"abstract":"<p><strong>Purpose: </strong>For locally-acting dry powder inhalers (DPIs), developing novel analytical tools that are able to evaluate the state of aggregation may provide a better understanding of the impact of material properties and processing parameters on the in vivo performance. This study explored the utility of the Morphologically-Directed Raman Spectroscopy (MDRS) and dissolution as orthogonal techniques to assess microstructural equivalence of the aerosolized dose of DPIs collected with an aerosol collection device.</p><p><strong>Methods: </strong>Commercial DPIs containing different strengths of Fluticasone Propionate (FP) and Salmeterol Xinafoate (SX) as monotherapy and combination products were sourced from different regions. These inhalers were compared with aerodynamic particle size distribution (APSD), dissolution, and MDRS studies.</p><p><strong>Results: </strong>APSD testing alone might not be able to explain differences reported elsewhere in in vivo studies of commercial FP/SX drug products with different Advair® strengths and/or batches. Dissolution studies demonstrated different dissolution rates between Seretide™ 100/50 and Advair® 100/50, whereas Flixotide™ 100 and Flovent® 100 had similar dissolution rates between each other. These differences in dissolution profiles were supported by MDRS results: the dissolution rate is increased if the fraction of FP associated with high soluble components is increased. Principle component analysis was used to identify the agglomerate classes that better discriminate different products.</p><p><strong>Conclusions: </strong>MDRS and dissolution studies of the aerosolized dose of DPIs were successfully used as orthogonal techniques. This study highlights the importance of further assessing in vitro tools that are able to provide a bridge between material attributes or process parameters and in vivo performance.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"2015-2029"},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392352","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}

{"title":"Correction: Fecal SN-38 Content as a Surrogate Predictor of Intestinal SN-38 Exposure and Associated Irinotecan-induced Severe Delayed-Onset Diarrhea by a Novel Use of the Spectrofluorimetric Method.","authors":"Zicong Zheng, Vesna Tumbas Šaponjac, Rashim Singh, Jie Chen, Songpol Srinual, Taijun Yin, Rongjin Sun, Ming Hu","doi":"10.1007/s11095-024-03774-3","DOIUrl":"10.1007/s11095-024-03774-3","url":null,"abstract":"","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"2075"},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351912","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":"Impact of Different Packaging Configurations on A Topical Cream Product.","authors":"Yousuf H Mohammed, S N Namjoshi, K C Telaprolu, N Jung, H M Shewan, J R Stokes, H A E Benson, J E Grice, S G Raney, E Rantou, Maike Windbergs, Michael S Roberts","doi":"10.1007/s11095-024-03772-5","DOIUrl":"10.1007/s11095-024-03772-5","url":null,"abstract":"<p><strong>Purpose: </strong>The objective of this study was to investigate whether different dispensing processes can alter the physicochemical and structural (Q3) attributes of a topical cream product, and potentially alter its performance.</p><p><strong>Methods: </strong>Acyclovir cream, 5% (Zovirax®) is sold in the UK and other countries in a tube and a pump packaging configurations. The structural attributes of the cream dispensed from each packaging configuration were analyzed by optical microscopy, confocal Raman microscopy and cryo-scanning electron microscopy. Rheological behavior of the products was also evaluated. Product performance (rate and extent of skin delivery) was assessed by in vitro permeation tests (IVPT) using heat-separated human epidermis mounted in static vertical (Franz-type) diffusion cells.</p><p><strong>Results: </strong>Differences in Q3 attributes and IVPT profiles were observed with creams dispensed from the two packaging configurations, even though the product inside each packaging appeared to be the same in Q3 attributes. Visible globules were recognized in the sample dispensed from the pump, identified as dimethicone globules by confocal Raman microscopy. Differences in rheological behaviour could be attributed to these globules as products not dispensed through the pump, demonstrated a similar rheological behaviour. Further, IVPT confirmed a reduced rate and extent to delivery across human epidermis from the product dispensed through a pump.</p><p><strong>Conclusions: </strong>Different methods of dispensing topical semisolid products can result in metamorphosis and Q3 changes that may have the potential to alter the bioavailability of an active ingredient. These findings have potential implications for product developers and regulators, related to the manufacturing and comparative testing of reference standard and prospective generic products dispensed from different packaging configurations.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"2043-2056"},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351922","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}

{"title":"Correction: Practical Advice on Scientific Design of Freeze-Drying Process: 2023 Update.","authors":"Serguei Tchessalov, Vito Maglio, Petr Kazarin, Alina Alexeenko, Bakul Bhatnagar, Ekneet Sahni, Evgenyi Shalaev","doi":"10.1007/s11095-024-03768-1","DOIUrl":"10.1007/s11095-024-03768-1","url":null,"abstract":"","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"2077"},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392336","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}

{"title":"Therapeutic Effects of Metformin on Central Nervous System Diseases: A Focus on Protection of Neurovascular Unit.","authors":"Chunyang Cai, Chufeng Gu, Chunren Meng, Shuai He, Lhamo Thashi, Draga Deji, Zhi Zheng, Qinghua Qiu","doi":"10.1007/s11095-024-03777-0","DOIUrl":"10.1007/s11095-024-03777-0","url":null,"abstract":"<p><p>Metformin is one of the most commonly used oral hypoglycemic drugs in clinical practice, with unique roles in neurodegeneration and vascular lesions. Neurodegeneration and vasculopathy coexist in many diseases and typically affect the neurovascular unit (NVU), a minimal structural and functional unit in the central nervous system. Its components interact with one another and are indispensable for maintaining tissue homeostasis. This review focuses on retinal (diabetic retinopathy, retinitis pigmentosa) and cerebral (ischemic stroke, Alzheimer's disease) diseases to explore the effects of metformin on the NVU. Metformin has a preliminarily confirmed therapeutic effect on the retinal NUV, affecting many of its components, such as photoreceptors (cones and rods), microglia, ganglion, Müller, and vascular endothelial cells. Since it rapidly penetrates the blood-brain barrier (BBB) and accumulates in the brain, metformin also has an extensively studied neuronal protective effect in neuronal diseases. Its mechanism affects various NVU components, including pericytes, astrocytes, microglia, and vascular endothelial cells, mainly serving to protect the BBB. Regulating the inflammatory response in NVU (especially neurons and microglia) may be the main mechanism of metformin in improving central nervous system related diseases. Metformin may be a potential drug for treating diseases associated with NVU deterioration, however, more trials are needed to validate its timing, duration, dose, clinical effects, and side effects.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"1907-1920"},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392354","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":"Population Pharmacokinetics of Casirivimab and Imdevimab in Pediatric and Adult Non-Infected Individuals, Pediatric and Adult Ambulatory or Hospitalized Patients or Household Contacts of Patients Infected with SARS-COV-2","authors":"Kuan-Ju Lin, Kenneth C. Turner, Maria Rosario, Lutz O. Harnisch, John D. Davis, A. Thomas DiCioccio","doi":"10.1007/s11095-024-03764-5","DOIUrl":"https://doi.org/10.1007/s11095-024-03764-5","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>Casirivimab (CAS) and imdevimab (IMD) are two fully human monoclonal antibodies that bind different epitopes on the receptor binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and block host receptor interactions. CAS + IMD and was developed for the treatment and prevention of SARS-CoV-2 infections.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>A population pharmacokinetic (PopPK) analysis was conducted using pooled data from 7598 individuals from seven clinical studies to simultaneously fit concentration–time data of CAS and IMD and investigate selected covariates as sources of variability in PK parameters. The dataset comprised CAS + IMD-treated pediatric and adult non-infected individuals, ambulatory or hospitalized patients infected with SARS-CoV-2, or household contacts of patients infected with SARS-CoV-2.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>CAS and IMD concentration–time data were both appropriately described simultaneously by a two-compartment model with first-order absorption following subcutaneous dose administration and first-order elimination. Clearance estimates of CAS and IMD were 0.193 and 0.236 L/day, respectively. Central volume of distribution estimates were 3.92 and 3.82 L, respectively. Among the covariates identified as significant, body weight and serum albumin had the largest impact (20–34%, and ~ 7–31% change in exposures at extremes, respectively), while all other covariates resulted in small differences in exposures. Application of the PopPK model included simulations to support dose recommendations in pediatrics based on comparable exposures of CAS and IMD between different weight groups in pediatrics and adults following weight-based dosing regimens.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>This analysis provided important insights to characterize CAS and IMD PK simultaneously in a diverse patient population and informed pediatric dose selection.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":"19 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260843","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":"The Use of Systemically Absorbed Drugs to Explore An In Vitro Bioequivalence Approach For Comparing Non-Systemically Absorbed Active Pharmaceutical Ingredients in Drug Products For Use in Dogs","authors":"Marilyn N. Martinez, Raafat Fahmy, Linge Li, Kithsiri Herath, R. Gary Hollenbeck, Ahmed Ibrahim, Stephen W. Hoag, David Longstaff, Shasha Gao, Michael J. Myers","doi":"10.1007/s11095-024-03766-3","DOIUrl":"https://doi.org/10.1007/s11095-024-03766-3","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>Currently, for veterinary oral formulations containing one or more active pharmaceutical ingredient (API) that are not systemically absorbed and act locally within the gastrointestinal (GI) tract, the use of terminal clinical endpoint bioequivalence (BE) studies is the only option for evaluating product BE. This investigation explored the use of a totality of evidence approach as an alternative to these terminal studies.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Three formulations of tablets containing ivermectin plus praziquantel were manufactured to exhibit distinctly different in vitro release characteristics. Because these APIs are highly permeable, plasma drug concentrations served as a biomarker of in vivo dissolution. Tablets were administered to 27 healthy Beagle dogs (3-way crossover) and the rate and extent of exposure of each API for each formulation was compared in a pairwise manner. These results were compared to product relative in vitro dissolution profiles in 3 media. In vivo and in vitro BE predictions were compared.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>In vivo/in vitro inconsistencies in product relative performance were observed with both compounds when considering product performance across the 3 dissolution media. Formulation comparisons flagged major differences that could explain this outcome.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>The finding of an inconsistent in vivo/in vitro relationship confirmed that in vitro dissolution alone cannot assure product BE for veterinary locally acting GI products. However, when combined with a comparison of product composition and manufacturing method, this totality of evidence approach can successfully alert scientists to potential therapeutic inequivalence, thereby supporting FDA’s efforts to Replace, Reduce, and/or Refine terminal animal studies.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":"8 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142221638","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":"Retraction Note: Verapamil Inhibits Ser202/Thr205 Phosphorylation of Tau by Blocking TXNIP/ROS/p38 MAPK Pathway.","authors":"Mariarosa Anna Beatrice Melone, Clemente Dato, Simona Paladino, Cinzia Coppola, Claudia Trebini, Maria Teresa Giordana, Lorena Perrone","doi":"10.1007/s11095-024-03767-2","DOIUrl":"10.1007/s11095-024-03767-2","url":null,"abstract":"","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"1905"},"PeriodicalIF":3.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142293126","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":"Fecal SN-38 Content as a Surrogate Predictor of Intestinal SN-38 Exposure and Associated Irinotecan-induced Severe Delayed-Onset Diarrhea by a Novel Use of the Spectrofluorimetric Method.","authors":"Zicong Zheng, Vesna Tumbas Šaponjac, Rashim Singh, Jie Chen, Songpol Srinual, Taijun Yin, Rongjin Sun, Ming Hu","doi":"10.1007/s11095-024-03755-6","DOIUrl":"10.1007/s11095-024-03755-6","url":null,"abstract":"<p><strong>Background: </strong>Irinotecan administration can lead to severe delayed-onset diarrhea (SDOD) in clinical practice. Currently, there is no reliable surrogate predictor of intestinal exposure to SN-38 and subsequent diarrhea incidence.</p><p><strong>Methods: </strong>The relationship between fecal 7-ethyl-10-hydroxycamptothecin (SN-38) content and SDOD was investigated in Fisher 344 rats using a novel spectrofluorimetric method. Additionally, a pharmacokinetic study of irinotecan was performed to evaluate the biodistribution of SN-38 to establish the relationship between tissue and fecal SN-38 exposure.</p><p><strong>Results: </strong>The spectrofluorimetric method was successfully employed to measure fecal SN-38 and CPT-11 content from Day 3 to Day 6 post-irinotecan administration. Only fecal SN-38 content on Day 3 exhibited a significantly positive correlation with SDOD incidence on Days 4 and 5. A cutoff value of SN-38 ≥ 0.066 mg/g in feces was identified, predicting severe diarrhea incidence with 81% accuracy and 80% specificity. The positive correlation between fecal SN-38 content and SN-38 exposure in the ileum on Day 3 was also reflected in the changes of indicators during intestinal injury, such as prostaglandin E2 level and antioxidant activity.</p><p><strong>Conclusion: </strong>Fecal SN-38 content proves to be representative of intestinal exposure to SN-38, indicative of intestinal injury, and predictive of SDOD incidence in rats, while the spectrofluorimetric method demonstrates the translational potential.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"1855-1867"},"PeriodicalIF":3.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976267","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}