Suguru Asaji, Yuta Funai, Yuta Seki, Ikumi Tamai, Yoshiyuki Shirasaka
{"title":"Contributions of multiple transport mechanisms to intestinal uptake of serotonin.","authors":"Suguru Asaji, Yuta Funai, Yuta Seki, Ikumi Tamai, Yoshiyuki Shirasaka","doi":"10.1016/j.xphs.2024.07.020","DOIUrl":"10.1016/j.xphs.2024.07.020","url":null,"abstract":"<p><p>This study aimed to analyze the contributions of multiple transport mechanisms to the intestinal uptake of serotonin (5-HT) by employing a variety of in vitro experimental techniques, focusing on organic cation transporters expressed in the gastrointestinal (GI) tract, such as SERT, PMAT, THTR2, OCT3, and OCTN2. Analysis of the concentration dependence of 5-HT uptake by Caco-2 cells revealed multi-affinity kinetics with high-affinity and low-affinity components, suggesting that multiple transporters are involved in the intestinal 5-HT uptake. Comparative analysis of transporters using K<sub>m</sub> values obtained in Xenopus oocyte expression systems suggested that SERT is responsible for the high-affinity transport, while PMAT, THTR2, and OCT3 contribute to the low-affinity transport. Further analysis indicated that the relative contributions of SERT and PMAT to the intestinal 5-HT uptake (0.01 µM) are approximately 94.9% and 1.1%, respectively. Interestingly, at the concentration of 10 µM, the reported steady-state concentration of 5-HT in the human colon, the contributions of SERT, PMAT, THTR2, and OCT3 were estimated to be approximately 37.0%, 1.0%, 18.2%, and 20.5%, respectively. In conclusion, the present study indicated that the contributions of multiple transporters to 5-HT uptake in the GI tract are dependent upon the colon luminal concentration of 5-HT.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289713","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":"Improved Properties of Glass Vials for Primary Packaging with Atomic Layer Deposition.","authors":"Ilkka Manninen, Riina Ritasalo, Samuli Hirsjärvi","doi":"10.1016/j.xphs.2024.09.007","DOIUrl":"https://doi.org/10.1016/j.xphs.2024.09.007","url":null,"abstract":"<p><p>Novel pharmaceuticals and drug delivery devices may require better performance from the packaging material e.g., in terms of extractables and leachables, and unwanted interactions. To address this, we applied atomic layer deposition (ALD) to build nanometer-range SiO<sub>2</sub>, ZrO<sub>2</sub> and Al<sub>2</sub>O<sub>3</sub>-TiO<sub>2</sub> films on primary packaging glass. Controlled modification of the surface also enabled creation of functionality without affecting visual appearance of the material. ALD-coated Type I borosilicate vials were compared to uncoated ones, and tailored functionality was presented by appropriate measurements. The tested ALD coatings formed a barrier on glass against extractables and leachables, from the vial and the coating alike. A good ALD coating prevents any leakage into the stored drug product. Hydrolytic resistance results improved by 85-92 %, and these results correlated well with straightforward water conductivity measurements. Opposite to uncoated borosilicate glass vials, no extracted elements could be detected from the extracts of the coated vials with stable ALD films. Improved surface integrity was observed with electron microscopy as well. ALD films increased hydrophilicity of the surface and tuning the ALD film thickness and composition allowed precise blocking of UV light wavelengths, without affecting transparency. As a conclusion, ALD is a versatile method to create barrier and functional films on primary packaging materials.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289715","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":"An overview of interpretability of two models of unbound fraction that are used in combination with the well-stirred model for predicting hepatic clearance of drugs.","authors":"Patrick Poulin","doi":"10.1016/j.xphs.2024.09.002","DOIUrl":"https://doi.org/10.1016/j.xphs.2024.09.002","url":null,"abstract":"<p><p>Hypothetical and experimental models of unbound fraction have been proposed to facilitate predicting the hepatic clearance (CL<sub>H</sub>) of drugs from values of intrinsic clearance for the unbound drug (CL<sub>int-in vitro-unbound</sub>) and the well-stirred model (WSM). The hypothetical model (fu<sub>-adjusted</sub>) is adjusting the unbound fractions determined in plasma in vitro to estimate the maximum unbound fractions at the hepatocytes if each drug-protein complex in plasma becomes fully dissociated at the membrane by any albumin (ALB)-facilitated hepatic uptake mechanism. The model of fu<sub>-adjusted</sub> is also adjusting the unbound fraction for a pH gradient effect across the membrane. Alternatively, the new experimental model (fu<sub>-dynamic</sub>) measures the unbound fractions resulting to the dynamic dissociation kinetics from proteins in the presence of plasma and a liver enzyme in an in vitro assay. The objective of this study was to conduct an in-depth analysis of previous CL<sub>H</sub> predictions made with these unbound fractions in a companion manuscript. Furthermore, a new dataset on transporter substrates was also included in this study. Finally, the physiological basis of fu<sub>-adjusted</sub> has been redefined to extend its applicability with more drugs. In this case, there are lower concentrations of binding proteins in liver versus plasma that could also explain the higher unbound fractions for that organ. The outcomes associated to additional analyses pointed out that fu<sub>-adjusted</sub>, again, generally provided the most accurate predictions of CL<sub>H</sub> because fu<sub>-dynamic</sub> has generated superior biases of underpredictions or overpredictions. For slowly metabolized drugs bound to ALB, fu<sub>-dynamic</sub> was definitively less accurate than fu<sub>-adjusted</sub>. For other drug properties, fu<sub>-dynamic</sub> fared better but it was still not generally more accurate than fu<sub>-adjusted</sub>. Furthermore, experimental values of fu<sub>-dynamic</sub> were sometimes incoherent. For example, drugs bound to alpha-acid glycoprotein (AGP) did not follow the principle of fu<sub>-dynamic</sub> (i.e., values of fu<sub>-dynamic</sub> did not correlate with values of CL<sub>int-in vitro-unbound</sub>) by contrast to those drugs bound to ALB. Therefore, the current experimental setting for fu<sub>-dynamic</sub> might be unsuitable in some circumstances. Overall, this study confirmed that calculated values of fu<sub>-adjusted</sub> were as accurate as experimental values of fu<sub>-dynamic</sub> and can even be more accurate. A guidance on which unbound fraction to use in the WSM is also provided.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289711","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}
Jeffrey D Clogston, Willard Foss, David Harris, Hardeep Oberoi, Jiayi Pan, Elaine Pu, Elisa A Torrico Guzmán, Katrin Walter, Scott Brown, Patrick Lim Soo
{"title":"Current state of nanomedicine drug products: An industry perspective.","authors":"Jeffrey D Clogston, Willard Foss, David Harris, Hardeep Oberoi, Jiayi Pan, Elaine Pu, Elisa A Torrico Guzmán, Katrin Walter, Scott Brown, Patrick Lim Soo","doi":"10.1016/j.xphs.2024.09.005","DOIUrl":"10.1016/j.xphs.2024.09.005","url":null,"abstract":"<p><p>Nanomedicine drug products have reached an unprecedented high in terms of global commercial acceptance and media exposure with the approvals of the mRNA COVID-19 vaccines in 2021. In this paper, we examine the current state of the art for nanomedicine technologies as applied for pharmaceutical products and compare those trends with results from a recent IQ Consortium industry survey on nanomedicine drug products. We find that 1) industry companies continue to push the envelope in terms of new technologies for characterizing their specific drug products, 2) new analytical technologies continue to be utilized by industry to characterize the increasingly complex nanomedicine drug products and 3) alignment and communication are key between industry and regulatory authorities to better understand the regulatory filings that are being submitted. There are many CMC challenges that a company must overcome to successfully file a nanomedicine drug product. In 2022, the FDA Guidance on Drug Products containing Nanomaterials was published, and it provides a roadmap for submission of a nanomedicine drug product. We propose that our paper serves as a complimentary guide providing knowledge on specific CMC issues such as quality attributes, physicochemical characterization methods, excipients, and stability.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289714","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":"A Novel Encapsulation Approach to Enhance the Delivery and Antitumor Activity of Docetaxel in Breast Cancer Therapy.","authors":"Shabnam Ghasedi, Vahab Jafarian, Yasaman Ghajari, Abbas Bahari, Mahsa Mekanik, Saeid Taghavi Fardood","doi":"10.1016/j.xphs.2024.09.010","DOIUrl":"10.1016/j.xphs.2024.09.010","url":null,"abstract":"<p><p>Docetaxel (DTX) is one of the most potent anticancer drugs but its extensive side effects necessitate innovative formulations. In this study, we aimed to investigate the expression pattern of apoptotic proteins, cell cycle arrest, and apoptosis induction after treatment with encapsulated DTX in alginate-chitosan nanoparticles in both breast cancer cells (MCF-7) and peripheral blood mononuclear cells (PBMCs). The characterization of the nanoparticles revealed a spherical shape with a size <50 nm, a hydrodynamic diameter of 200 nm, a Polydispersity Index of 0.5, and an encapsulation efficiency of 98.75 %. The free drug was released completely within 11 h while encapsulated DTX was released only 34 % in 96 h. The encapsulated drug indicated higher cytotoxicity on MCF-7 cells and the half inhibitory concentration (IC<sub>50</sub>) value was 2 µg/ml after 72 h. Quantitative real-time PCR demonstrated a significant increase in cell death as the expression of apoptosis regulatory protein (Bcl-2) was downregulated with no impact on Bax in the MCF-7 cells. A notable decrease in the expression pattern of pro-inflammatory cytokine (IL-1β) in PBMCs indicated less inflammation induction. Flow cytometry analysis revealed that the newly formulated drug induced less opoptosis in PBMCs than the free DTX. Cell cycle arrest in the sub-G<sub>1</sub> phase was observed for the free drug while the encapsulated drug exhibited no significant changes. Our results suggest the high toxicity of the formulated drug in contrast to the free DTX on the MCF-7 cell line, minimal blood cell side effects, and no inflammation positioning it as a promising alternative to free docetaxel.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289696","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}
Adeola O Coker, Cynthia A Oksanen, Tina Morris, Kristen Kalmann
{"title":"Is access to leadership roles contributing to the gender pay gap in the pharmaceutical sciences?","authors":"Adeola O Coker, Cynthia A Oksanen, Tina Morris, Kristen Kalmann","doi":"10.1016/j.xphs.2024.08.018","DOIUrl":"10.1016/j.xphs.2024.08.018","url":null,"abstract":"<p><p>Gender disparity in the pharmaceutical sciences contributes to the overall gender pay gap. The gender pay inequity is worse at later career stages. Salary data for pharmaceutical scientists has been reviewed from both the American Association of Pharmaceutical Sciences (AAPS) Salary Survey and the American Association of Colleges of Pharmacy (AACP) Pharmacy Faculty Demographics and Salaries report. We share some potential causes of the pay inequity, including implicit bias, pipeline issues, family responsibilities, and others. We suggest how organizations can put processes in place to help narrow the gender pay gap. Additionally, we share suggestions for how women must take a proactive role to ensure they reach their full potential and pay equity.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289716","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":"Drug Delivery from A Ring Implant Attached to Intraocular Lens: An In-Silico Investigation.","authors":"Pawan Kumar Pandey, Manish Jain, Prateek K Jha","doi":"10.1016/j.xphs.2024.09.001","DOIUrl":"10.1016/j.xphs.2024.09.001","url":null,"abstract":"<p><p>Multiple iterations required to design ocular implants, which will last for the desired operational period of months or even years, necessitate the use of in-silico models for ocular drug delivery. In this study, we developed an in-silico model to simulate the flow of Aqueous Humor (AH) and drug delivery from an implant to the Trabecular Meshwork (TM). The implant, attached to the side of the intraocular lens (IOL), and the TM are treated as porous media, with their effects on AH flow accounted for using the Darcy equation. This model accurately predicts the physiological values of Intraocular Pressure (IOP) for both healthy individuals and glaucoma patients, as reported in the literature. Results reveal that the effective diffusivity of the drug within the implant is the critical parameter that can alter the bioavailability time period (BTP) from a few days to months. Intuitively, BTP should increase as effective diffusivity decreases. However, we discovered that with lower levels of initial drug loading, BTP declines when effective diffusivity falls below a specific threshold. Our findings further reveal that, while AH flow has a minimal effect on the drug release profile at the implant site, it significantly impacts drug availability at the TM.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154452","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}
Zhuo-Wei Shen, Xiu-Yan Yang, Lu Han, Xi Yang, Jiao Xie, Xiao-Qin Liu, Jue-Hui Mao, Hao-Ran Dai, Wei-Wei Kong, Xiao-Ying Wu, Yun-Qing Qiu, Hong-Feng Huang, Yan Lou
{"title":"Optimizing the dosing regimen of roxadustat in kidney transplant recipients with early post-transplant anemia.","authors":"Zhuo-Wei Shen, Xiu-Yan Yang, Lu Han, Xi Yang, Jiao Xie, Xiao-Qin Liu, Jue-Hui Mao, Hao-Ran Dai, Wei-Wei Kong, Xiao-Ying Wu, Yun-Qing Qiu, Hong-Feng Huang, Yan Lou","doi":"10.1016/j.xphs.2024.09.004","DOIUrl":"https://doi.org/10.1016/j.xphs.2024.09.004","url":null,"abstract":"<p><strong>Introduction: </strong>Roxadustat, an oral inhibitor of hypoxia-inducible factor prolyl hydroxylase domain enzymes, has been approved for the treatment of renal anemia. However, there is a lack of study on its pharmacokinetics in kidney transplant recipients (KTRs) with early posttransplant anemia (PTA). Therefore, the aim of this study is to elucidate the pharmacokinetic characteristics of roxadustat in KTRs with early PTA and optimize the dosing regimen.</p><p><strong>Methods: </strong>A population pharmacokinetic (PopPK) analysis was performed based on 72-hour full concentration-time profiles collected from 52 Chinese KTRs. Covariates influencing exposure were assessed using stepwise covariate modelling. Monte Carlo simulations were conducted to recommend the dosing regimen for patients with different levels of covariates.</p><p><strong>Results: </strong>PopPK analysis showed that the concentration-time data can be fully described by a two-compartment model. Body weight (BW) and direct bilirubin (DBIL) levels significant affected the apparent clearance of roxadustat. Based on the established model and the estimated exposures of roxadustat by Monte Carlo simulations, a recommended dosing regimen for KTRs with early PTA at varying BW and DBIL levels were developed. Roxadustat at 100 mg three times weekly were suitable for the majority of KTRs with a DBIL level around 3 μmol/L and BW between 50 and 75 kg. The required dose may need to be increased with higher BW and lower DBIL levels, while decreased with lower BW and higher DBIL levels.</p><p><strong>Conclusions: </strong>It was the first PopPK analysis of roxadustat in KTRs with early PTA, which provide a research basis for optimizing the dosing regimen.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289718","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":"Physiologically based pharmacokinetic model of brivaracetam to predict the exposure and dose exploration in hepatic impairment and elderly populations.","authors":"Yiming Li, Wenxin Shao, Xingwen Wang, Kuo Geng, Wenhui Wang, Zhiwei Liu, Youjun Chen, Chaozhuang Shen, Haitang Xie","doi":"10.1016/j.xphs.2024.08.022","DOIUrl":"10.1016/j.xphs.2024.08.022","url":null,"abstract":"<p><p>Brivaracetam (BRV) is a new third-generation antiseizure medication for the treatment of focal epileptic seizures. Its use has been increasing among epileptic populations in recent years, but pharmacokinetic (PK) behavior may change in hepatic impairment and the elderly populations. Due to ethical constraints, clinical trials are difficult to conduct and data are limited. This study used PK-Sim® to develop a physiologically based pharmacokinetic (PBPK) model for adults and extrapolate it to hepatic impairment and the elderly populations. The model was evaluated with clinical PK data, and dosage explorations were conducted. For the adult population with mild hepatic impairment, the dose is recommended to be adjusted to 70 % of the recommended dose, and to 60 % for moderate and severe hepatic impairment. For the elderly population with mild hepatic impairment under 80 years old, it is recommended that the dose be adjusted to 60 % of the recommended dose and to 50 % for moderate and severe conditions. The elderly population with hepatic impairment over 80 years old is adjusted to 50 % of the recommended dose for all stages. Healthy elderly do not need to adjust. The BRV PBPK model was successfully developed, studying exposure in hepatic impairment and elderly populations and optimizing dosing regimens.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145858","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":"Chemistry and Ionization of HPMCAS Influences the Dissolution and Solution-Mediated Crystallization of Posaconazole Amorphous Solid Dispersions.","authors":"Dishan D Shah, Lynne S Taylor","doi":"10.1016/j.xphs.2024.08.023","DOIUrl":"10.1016/j.xphs.2024.08.023","url":null,"abstract":"<p><p>Hydroxypropyl methyl cellulose acetate succinate (HPMCAS) is one of the polymers of choice in formulating amorphous solid dispersions (ASDs) and helps to sustain high levels of drug supersaturation by delaying drug crystallization. Herein, the impact of HPMCAS chemistry on the solution crystallization kinetics of a fast-crystallizing lipophilic drug, posaconazole (PCZ), from the aqueous bulk phase and the drug-rich phase generated by liquid-liquid phase separation (LLPS), was studied. Three grades of HPMCAS: L, M, and H, which differ in the degree of acetyl and succinoyl substitution (A/S ratio), were compared. The influence of the polymers on the nucleation induction time, and LLPS concentration of PCZ, as well as the size, ζ-potential and composition of the nano-sized drug-rich phase was determined. An increase in the nucleation induction time was observed with an increase in the polymer A/S ratio. A blue shift in the fluorescence emission spectrum of PCZ suggested a greater extent of interaction between PCZ and HPMCAS with an increase in the A/S ratio. More polymer partitioning into the drug-rich phase was also observed with an increase in the A/S ratio, resulting in smaller droplets. A greater extent of ionization of HPMCAS upon increasing the pH from 5.5 to 7.5 decreased the hydrophobicity of the polymer resulting in shorter nucleation induction times. The phase behavior of PCZ in ASD release studies was consistent with these observations, where the shortest duration of supersaturation was observed with the L grade. Although the H grade provided the best inhibition of crystallization, complete release was only observed at higher pH. HPMCAS grade thus influences the kinetics of PCZ crystallization following release from an ASD, as well as the extent of release at physiologically relevant pH conditions. This study provides insights into the role of HPMCAS chemistry and ionization as factors influencing its ability to act as a crystallization inhibitor.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145857","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}