Journal of pharmaceutical sciences最新文献_第3页

Improved properties of glass vials for primary packaging with atomic layer deposition 利用原子层沉积技术改善初级包装用玻璃瓶的性能。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-11-01 DOI: 10.1016/j.xphs.2024.09.007

Ilkka Manninen , Riina Ritasalo , Samuli Hirsjärvi

{"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":"10.1016/j.xphs.2024.09.007","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"113 11","pages":"Pages 3354-3361"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Microparticles incorporating dual apoptotic factors to inhibit inflammatory effects in macrophages 含有双重凋亡因子的微颗粒可抑制巨噬细胞的抗炎作用。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-11-01 DOI: 10.1016/j.xphs.2024.05.030

Sean R. Simpson , Denzel D. Middleton , Nicole Rose Lukesh , Md Jahirul Islam , Stephen A. Ehrenzeller , Eric M. Bachelder , Kristy M. Ainslie

{"title":"Microparticles incorporating dual apoptotic factors to inhibit inflammatory effects in macrophages","authors":"Sean R. Simpson , Denzel D. Middleton , Nicole Rose Lukesh , Md Jahirul Islam , Stephen A. Ehrenzeller , Eric M. Bachelder , Kristy M. Ainslie","doi":"10.1016/j.xphs.2024.05.030","DOIUrl":"10.1016/j.xphs.2024.05.030","url":null,"abstract":"<div><div>New approaches to treat autoimmune diseases are needed, and we can be inspired by mechanisms in immune tolerance to guide the design of these approaches. Efferocytosis, the process of phagocyte-mediated apoptotic cell (AC) disposal, represents a potent tolerogenic mechanism that we could draw inspiration from to restore immune tolerance to specific autoantigens. ACs engage multiple avenues of the immune response to redirect aberrant immune responses. Two such avenues are: phosphatidylserine on the outer leaflet of the cell and engaging the aryl hydrocarbon receptor (AhR) pathway. We incorporated these two avenues into one acetalated dextran (Ace-DEX) microparticle (MP) for evaluation in vitro. First phosphatidylserine (PS) was incorporated into Ace-DEX MPs and evaluated for cellular association and mediators of cell tolerance including IL-10 production and M2 associated gene expression when particles were cultured with peritoneal macrophages (PMacs). Further PS Ace-DEX MPs were evaluated as an agent to suppress LPS stimulated PMacs. Then, AhR agonist 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) was incorporated into Ace-DEX MPs and expression of M2 and IL-10 genes was evaluated in PMacs. Further the ITE and PS Ace-DEX MPs (PS/ITE MPs) were evaluated for suppression of T cell priming and Th1 polarization. Our results indicate that the PS/ITE-MPs stimulated anti-inflammatory cytokine expression and suppressed inflammation following LPS stimulation of PMacs. Moreover, PS/ITE MPs induced the anti-inflammatory enzyme IDO1 and suppressed macrophage-mediated T cell priming and Th1 polarization. These findings suggest that PS and ITE-loaded Ace-DEX MPs could be a promising therapeutic tool for suppressing inflammation.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"113 11","pages":"Pages 3196-3205"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296284","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}

引用次数: 0

Predicting plasma protein binding of drugs in special populations: Are all models wrong, but can some be recalibrated, refined, and become more useful? 预测特殊人群血浆蛋白与药物的结合：是否所有模型都是错误的，但有些模型可以重新校准、改进并变得更有用？

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-11-01 DOI: 10.1016/j.xphs.2024.08.020

Guo-Fu Li, Guo Yu, Ming-Feng Li

引用次数: 0

A new ciprofibrate calcium salt with improved solubility and intrinsic dissolution rate 一种新的环丙贝特钙盐，其溶解度和内在溶解速率均有所提高。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-11-01 DOI: 10.1016/j.xphs.2024.08.025

Bruno Arantes Borges , Kassius de Souza Reis , Camila Batista Pinto , Javier Ellena , Antônio Carlos Doriguetto , Rudy Bonfilio

{"title":"A new ciprofibrate calcium salt with improved solubility and intrinsic dissolution rate","authors":"Bruno Arantes Borges , Kassius de Souza Reis , Camila Batista Pinto , Javier Ellena , Antônio Carlos Doriguetto , Rudy Bonfilio","doi":"10.1016/j.xphs.2024.08.025","DOIUrl":"10.1016/j.xphs.2024.08.025","url":null,"abstract":"<div><div>Ciprofibrate (CIP) is an active pharmaceutical ingredient (API) classified as class II on the basis of biopharmaceutical classification system (BCS), what indicates that it has low solubility in aqueous solvents. The use of API salts has attracted attention due to their improvements in solubility, tolerability, higher rate and extent of absorption, and faster onset of the therapeutic effect. In this work, a new crystalline CIP monohydrated calcium salt (Ca(CIP)<sub>2</sub>.H<sub>2</sub>O) was successfully obtained and its crystal structure determined by single crystal X-ray diffraction analysis (SCXRD). Additionally, Ca(CIP)<sub>2</sub>.H<sub>2</sub>O was widely characterized by powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and submitted to solubility, intrinsic dissolution and accelerated stability studies. Ca(CIP)<sub>2</sub>.H<sub>2</sub>O exhibited higher solubility and dissolution rate than CIP-free form and was stable up to 6 months at 40 °C (75 %RH). Therefore, Ca(CIP)<sub>2</sub>.H<sub>2</sub>O may be a viable alternative for use in solid dosage forms.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"113 11","pages":"Pages 3297-3303"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108579","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}

引用次数: 0

An unexpected degradation pathway of N-hydroxy-5-methylfuran-2-sulfonamide (BMS-986231), a pH sensitive prodrug of HNO, in a prototype formulation solution N-羟基-5-甲基呋喃-2-磺酰胺（BMS-986231）（一种对 pH 值敏感的 HNO 原药）在原型制剂溶液中的意外降解途径。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-11-01 DOI: 10.1016/j.xphs.2024.08.027

Yande Huang , Amy Sarjeant , Roger Sommer , Dhaval Patel , Qinggang Wang , Dilbir Bindra , Scott A. Miller

{"title":"An unexpected degradation pathway of N-hydroxy-5-methylfuran-2-sulfonamide (BMS-986231), a pH sensitive prodrug of HNO, in a prototype formulation solution","authors":"Yande Huang , Amy Sarjeant , Roger Sommer , Dhaval Patel , Qinggang Wang , Dilbir Bindra , Scott A. Miller","doi":"10.1016/j.xphs.2024.08.027","DOIUrl":"10.1016/j.xphs.2024.08.027","url":null,"abstract":"<div><div><em>N</em>-hydroxy-5-methylfuran-2-sulfonamide (BMS-986231, Cimlanod) was being developed as a pH-sensitive prodrug of HNO (nitroxyl) for the treatment of acute decompensated heart failure. During a stressed study of Cimlanod in a prototype formulation solution (pH 4.5) at 40°C, a predominant unknown degradant along with three previously identified degradants were observed. The unknown degradant was isolated from the stressed solution via preparative HPLC but totally decomposed during freeze-drying. LC-HRMS analysis of the isolated unknown degradant, prior to freeze-drying, revealed an empirical formula equivalent to the adduct of Cimlanod with SO<sub>2</sub> even though SO<sub>2</sub> was not added in the prototype formulation solution. The unknown degradant was synthesized from Cimlanod and DABSO ((1,4-diazabiscyclo[2,2,2]octane bis(sulfur dioxide) adduct) and isolated as a crystalline DABCO (1,4-diazabiscyclo[2,2,2]octane) salt for single crystal X-ray structure elucidation. The degradation of Cimlanod increased when the solution was exposed to air, as compared to N<sub>2</sub> atmosphere. A plausible mechanism was postulated for the unexpected degradation pathway of Cimlanod. This study provided in-depth stability knowledge of Cimlanod, which will be beneficial to the subsequent stability indicating method development and validation as well as the registrational applications on the content and qualification of impurities in new drug products.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"113 11","pages":"Pages 3315-3322"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108580","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}

引用次数: 0

Study of leachable compounds in hospital pharmacy-compounded prefilled syringes, infusion bags and vials 医院药房配制的预灌封注射器、输液袋和药瓶中可浸出化合物的研究。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-11-01 DOI: 10.1016/j.xphs.2024.08.004

William Bello , Julian Pezzatti , Serge Rudaz , Farshid Sadeghipour

{"title":"Study of leachable compounds in hospital pharmacy-compounded prefilled syringes, infusion bags and vials","authors":"William Bello , Julian Pezzatti , Serge Rudaz , Farshid Sadeghipour","doi":"10.1016/j.xphs.2024.08.004","DOIUrl":"10.1016/j.xphs.2024.08.004","url":null,"abstract":"<div><div>Hospital pharmacy compoundings are crucial for maintaining patient care. They are time- and cost-effective in hospital pharmacy settings because they prevent waste, preparation errors, dosage errors, microbial contamination and breakage due to handling. Unfortunately, the drawbacks of hospital pharmacy compounding include the selection of inappropriate medical devices (MDs) for long-term storage, which could directly impact patients.</div><div>In this study, three important hospital pharmaceutical compoundings, vancomycin in prefilled syringes (PFSs) made of polypropylene (PP) material, paediatric parenteral nutrition (PN) in ethylene vinyl acetate (EVA) bags and diluted insulin in cyclic olefin copolymer (COC) vials, were selected for leachate study and risk assessment. These compounds were studied via a semiquantitative screening approach by means of an ultrahigh-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) with postcolumn infusion and an in-house built database. 17 leachable compounds for the PFS, 25 for the PN, and 10 for the vial were identified, and their concentrations were estimated for toxicological assessments.</div><div>In conclusion, all MDs used in hospital pharmacy compoundings were observed suitable thanks to risk assessments. However, suitable MDs recommended for long-term storage would remain with polymers like COC, for higher safety when exposed to frail and vulnerable patients like neonates and infants.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"113 11","pages":"Pages 3227-3237"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036116","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}

引用次数: 0

Synthesis of thiomer/nanoclay nanocomposites as a potential drug carrier: Evaluation of mucoadhesive and controlled release properties 作为潜在药物载体的硫代物/纳米黏土纳米复合材料的合成：黏附性和控释性能评估

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-11-01 DOI: 10.1016/j.xphs.2024.08.030

Alexander Sepúlveda-Córdova, Tomás Fernández-Martínez, Víctor H. Campos-Requena

{"title":"Synthesis of thiomer/nanoclay nanocomposites as a potential drug carrier: Evaluation of mucoadhesive and controlled release properties","authors":"Alexander Sepúlveda-Córdova, Tomás Fernández-Martínez, Víctor H. Campos-Requena","doi":"10.1016/j.xphs.2024.08.030","DOIUrl":"10.1016/j.xphs.2024.08.030","url":null,"abstract":"<div><div>Novel thiomer/nanoclay nanocomposites based on a thiomer and montmorillonite (MMT) were prepared in order to obtain a mucoadhesive material with controlled release properties for its potential use as drug carrier. The thiomer was synthesized by immobilization of L-cysteine in alginate mediated by carbodiimide reaction and further characterized by FT-IR and Ellman's reaction. Nanocomposites with growing concentrations of thiomer and MMT were prepared and analyzed by XRD, TGA and TEM. Rheological behavior of nanocomposite in contact with mucin and intestinal mucus were studied as <em>in vitro</em> and <em>in situ</em> mucoadhesion approach, showing until ∼10-fold increasing in the complex viscosity and ∼27-fold in elastic modulus when the amount of thiomer is increased. Higuchi and Korsmeyer-Peppas kinetic models were evaluated in order to study the release of deltamethrin from nanocomposite films. Release profiles showed a retard in the migration of the drug influenced by the amount of MMT (<em>P</em> < 0.05). Diffusion coefficient (<em>D</em>) showed a significant decrease (<em>P</em> < 0.0001) when concentration of MMT is increased reaching <em>D</em> = 4.18 × 10<sup>–7</sup> m<sup>2</sup> h<sup>–1</sup>, which resulted ∼7-fold lower in comparison with formulation without MMT. This hybrid nanocomposite can be projected as a potential mucoadhesive drug carrier with controlled release properties.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"113 11","pages":"Pages 3323-3331"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108583","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}

引用次数: 0

Early clinical drug product shelf-life setting using accelerated predictive stability and metabolite data for impurity qualification: A case study 利用加速预测稳定性和代谢物数据进行杂质鉴定，确定早期临床药物产品的保质期：案例研究。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-11-01 DOI: 10.1016/j.xphs.2024.08.010

Jenny E. Ottosson , Angela Ku , Magnus Fransson , Carina Leandersson , Lars Weidolf , Jufang Wu Ludvigsson , Magnus Klarqvist

{"title":"Early clinical drug product shelf-life setting using accelerated predictive stability and metabolite data for impurity qualification: A case study","authors":"Jenny E. Ottosson , Angela Ku , Magnus Fransson , Carina Leandersson , Lars Weidolf , Jufang Wu Ludvigsson , Magnus Klarqvist","doi":"10.1016/j.xphs.2024.08.010","DOIUrl":"10.1016/j.xphs.2024.08.010","url":null,"abstract":"<div><div>This case study demonstrates how knowledge of degradation products together with predictions can establish a lean stability strategy using the accelerated predictive stability (APS) principles. Applying all available data for AZD4831, (R)-1-(2-(1-aminoethyl)-4-chlorobenzyl)-2-thioxo-2,3-dihydro-1H-pyrrolo[3,2-d]pyrimidin-4(5H)-one, a reliable predictive model was developed despite minor differences in technical batch tablet compositions. Early forced degradation studies were performed to map potential degradation pathways. The insights from these studies guided the design of an APS study, which in turn inform on a suitable clinical stability program, initial specification and shelf-life. The use of APS predictions of degradants as well as total impurities highlighted at an early stage, when designing the clinical stability program, the opportunity to identify which degradation product that would be shelf-life limiting. Hence, it was possible to guide the development stability activities and set an initial shelf-life of a tablet formulation. The presented study displays the importance of combining several sources of information in drug development, e.g., potential degradation pathways, accelerated stability, stability program design, metabolite data, and specification limits.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"113 11","pages":"Pages 3265-3271"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120108","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}

引用次数: 0

Rapid communication: A simple, non-invasive, cost-effective technique to monitor ice nucleation in GMP freeze-drying 快速交流：一种监测 GMP 冻干过程中冰核形成的简单、无创、经济高效的技术。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-11-01 DOI: 10.1016/j.xphs.2024.07.011

Jean-René Authelin , Evgenyi Shalaev

引用次数: 0

Drug delivery from a ring implant attached to intraocular lens: An in-silico investigation 眼内透镜环形植入物的药物输送：模拟研究

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-11-01 DOI: 10.1016/j.xphs.2024.09.001

Pawan Kumar Pandey , Manish Jain , Prateek K. Jha

{"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":"<div><div>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.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"113 11","pages":"Pages 3332-3343"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","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}

引用次数: 0