Journal of pharmaceutical sciences最新文献

{"title":"Impact of drug incorporation into micelle on reduced griseofulvin and meloxicam permeation across a hollow fiber membrane.","authors":"Roshni P Patel, Lynne S Taylor, James E Polli","doi":"10.1016/j.xphs.2024.10.017","DOIUrl":"10.1016/j.xphs.2024.10.017","url":null,"abstract":"<p><p>A hollow fiber membrane (HFM) was previously characterized as a potential permeation component of a dissolution/permeation system. Two objectives were to assess the impact of micellization on drug permeation across HFM and identify a preferred permeation model from three models: permeation from only free drug, permeation from both free drug and micelle-bound drug, and permeation with enhancement from micelle shuttling. HFM studies were conducted under unsaturated drug conditions, using griseofulvin and the more hydrophilic drug meloxicam, with and without surfactant [sodium lauryl sulfate, polysorbate 80, and polyoxyethylene (10) lauryl ether]. Griseofulvin was micelle incorporated to a greater extent than meloxicam, such that griseofulvin flux decreased to a greater extent than for meloxicam. The griseofulvin permeation model from only free drug was rejected, since griseofulvin flux required free drug to be about 5-20 fold higher in HFM flux studies than supported by solubility studies, depending on surfactant. Permeation from both free griseofulvin and micelle-bound griseofulvin successfully accommodated observed flux, where micelle permeability was about 5-fold lower than free drug permeability for HFM with 10 KDa MWCO. Permeation with enhancement from micelle shuttling was not the preferred explanation, although the model accommodated flux data and provided aqueous boundary layer thicknesses similar to other setups.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"402-415"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468291","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":"Simultaneous XRD-DSC identifies correct drug-polymer solubility and miscibility for enantiotropic solid forms.","authors":"Mustafa Bookwala, Jiawanjun Shi, Ira S Buckner, Simon Bates, Peter L D Wildfong","doi":"10.1016/j.xphs.2024.10.018","DOIUrl":"10.1016/j.xphs.2024.10.018","url":null,"abstract":"<p><p>Thermodynamic properties, including solubility and miscibility, which are highly correlated with amorphous solid dispersion physical stability were identified for the complex solid forms of bromopropamide using simultaneous X-ray diffraction (XRD)-differential scanning calorimetry (DSC). The most stable solid form of bromopropamide was crystallized and its crystal structure was solved. The crystallized material was characterized using simultaneous XRD-DSC measurements, which allowed dual analyses of a single sample. Transitions of bromopropamide during heating resulted in observation of the unique diffraction patterns of its different solid forms. The dissolution endpoint (T_end) was measured for various mixtures of bromopropamide and polyvinylpyrrolidone-vinyl acetate random copolymer (PVPVA). The use of XRD-DSC allowed confident and accurate measurements of the T_end for a large range of compositions, assisting in the estimation of drug-polymer solubility and miscibility. Thermodynamic properties identified using combined XRD-DSC were further compared to those obtained using only DSC data. It was found that DSC data in isolation can lead to ambiguity, misinterpretations, and incorrect conclusions, especially for a solid demonstrating multiple, closely related forms.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"416-423"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468299","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":"Delaying the first nucleation event of amorphous solid dispersions above the polymer overlap concentration (c*): PVP and PVPVA in posaconazole.","authors":"Sichen Song, Xin Yao, Chenguang Wang, Changquan Calvin Sun, Ronald A Siegel","doi":"10.1016/j.xphs.2024.04.026","DOIUrl":"10.1016/j.xphs.2024.04.026","url":null,"abstract":"<p><p>A thorough understanding of effects of polymers on crystallization of amorphous drugs is essential for rational design of robust amorphous solid dispersion (ASD), since crystallization of the amorphous drug negates their solubility advantage. In this work, we measured the first nucleation time (t₀, time to form the first critical nucleus in fresh liquid/glass) in posaconazole (POS)/polyvinylpyrrolidone vinyl acetate (PVPVA) and POS/polyvinylpyrrolidone (PVP K25) ASDs and showed that the polymer overlap concentration (c*, concentration above which adjacent polymer chains begin to contact) is critical in controlling crystallization of ASDs. When polymer concentration c < c*, t₀ of POS ASDs is approximately equal to that of the neat amorphous POS, but it increases significantly when c > c*. This observation supports the view that the effective inhibitory effect of crystallization in ASDs above c* is primarily correlated with delay in the first nucleation event. Our finding is useful in efficient polymer selection and performance prediction of high drug loaded ASD formulations.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"98-104"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140858197","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 integrated approach combining experimental, informatics and energetic methods for solid form derisking of PF-06282999.","authors":"Ghazala Sadiq, Shubham Sharma, Joanna S Stevens, Pablo Martinez-Bulit, Lily M Hunnisett, Christopher Cameron, Brian Samas, Emma Hawking, Nicholas Francia, Jeff Lengyel, Elna Pidcock, Sadia Rahman, Matthew Nisbet, Kevin Back, Cheryl Doherty, Patricia Basford, Timothy G Cooper, Garry O'Connor, Rajni M Bhardwaj","doi":"10.1016/j.xphs.2024.10.013","DOIUrl":"10.1016/j.xphs.2024.10.013","url":null,"abstract":"<p><p>The landscapes of observed and predicted three-dimensional crystal packing arrangements of small-molecule drug candidates can be complex. The possible appearance of a more thermodynamically stable solid form during drug development has led to the digital workflow of informatics-based risk assessments, named a Solid Form Health Check. Herein, we describe the use of a combined approach consisting of experiments, informatics together with energetic calculations in analysis of four competing polymorphs of PF-06282999, a myeloperoxidase (MPO) inhibitor with conformational flexibility and multiple plausible hydrogen bond networks. This combined approach offered a comprehensive understanding of the solid form structure, properties, and performance, ensuring robust solid form derisking and selection.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"371-382"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468267","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":"Cocrystal screening in minutes by solution-mediated phase transformation (SMPT): Preparation and characterization of ketoconazole cocrystals with nine aliphatic dicarboxylic acids.","authors":"Junguang Yu, Rodger F Henry, Geoff G Z Zhang","doi":"10.1016/j.xphs.2024.10.046","DOIUrl":"10.1016/j.xphs.2024.10.046","url":null,"abstract":"<p><p>The rapid and efficient cocrystal screening, based on solution-mediated phase transformation (SMPT), was applied to the screening of cocrystals between ketoconazole (KTZ) and nine aliphatic dicarboxylic acids. Cocrystals formed successfully, in minutes, with a change of suspension characteristics, either a cake formation or the formation of large particles. Bulk cocrystals were characterized by powder X-ray diffraction, thermal analysis, and Raman spectroscopy. Single crystals were grown, and molecular structures were determined. Three previously reported cocrystals were reproduced, and six new cocrystals were discovered, including one that was reported as a failure in literature by solution or grinding method. Two hydrogen-bonded motifs are observed in these nine cocrystals: Most cocrystals form hydrogen bonded discrete tetramer with two KTZ and two acids molecules; while two cocrystals form infinite chain. This study demonstrated the high efficacy of cocrystal generation using the slurry screening method. It should be fully utilized in future cocrystal screening.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"592-598"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546079","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":"Reprint of: M1 macrophage-targeted curcumin nanocrystals with l-arginine-modified for acute lung injury by inhalation.","authors":"Shiyue Wu, Pengchuan Guo, Qiren Zhou, Xiaowen Yang, Jundong Dai","doi":"10.1016/j.xphs.2024.12.001","DOIUrl":"10.1016/j.xphs.2024.12.001","url":null,"abstract":"<p><p>Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS) with clinical manifestations of respiratory distress and hypoxemia remains a significant cause of respiratory failure, boasting a persistently high incidence and mortality rate. Given the central role of M1 macrophages in the pathogenesis of acute lung injury (ALI), this study utilized the anti-inflammatory agent curcumin as a model drug. l-arginine (L-Arg) was employed as a targeting ligand, and chitosan was initially modified with l-arginine. Subsequently, it was utilized as a surface modifier to prepare inhalable nano-crystals loaded with curcumin (Arg-CS-Cur), aiming for specific targeting of pulmonary M1 macrophages. Compared with unmodified chitosan-curcumin nanocrystals (CS-Cur), Arg-CS-Cur exhibited higher uptake in vitro by M1 macrophages, as evidenced by flow cytometry showing the highest fluorescence intensity in the Arg-CS-Cur group (P < 0.01). In vivo accumulation was greater in inflamed lung tissues, as indicated by small animal imaging demonstrating higher lung fluorescence intensity in the DiR-Arg-CS-Cur group compared to the DiR-CS-Cur group in the rat ALI model (P < 0.05), peaking at 12 h. Moreover, Arg-CS-Cur demonstrated enhanced therapeutic effects in both LPS-induced RAW264.7 cells and ALI rat models. Specifically, treatment with Arg-CS-Cur significantly suppressed NO release and levels of TNF-α and IL-6 in RAW264.7 cells (p < 0.01), while in ALI rat models, expression levels of TNF-α and IL-6 in lung tissues were significantly lower than those in the model group (P < 0.01). Furthermore, lung tissue damage was significantly reduced, with histological scores significantly lower than those in the CS-Cur group (P < 0.01). In conclusion, these findings underscore the targeting potential of l-arginine-modified nanocrystals, which effectively enhance curcumin concentration in inflammatory environments by selectively targeting M1 macrophages. This study thus introduces novel perspectives and theoretical support for the development of targeted therapeutic interventions for acute inflammatory lung diseases, including ALI/ARDS.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"105-118"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801200","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":"Implications of crystal disorder on the solid-state stability of olanzapine.","authors":"Jayant Iyer, Matilde Barbosa, João F Pinto, Amrit Paudel","doi":"10.1016/j.xphs.2024.10.047","DOIUrl":"10.1016/j.xphs.2024.10.047","url":null,"abstract":"<p><p>Mechanical perturbations of drug during solid pharmaceutical processing like milling can often generate crystal disorder posing serious implications to drug's stability. While physical changes like amorphization, recrystallization, polymorphism of the disordered drugs are extensively studied and reported in the literature, the propensities and inter-dependencies of recrystallization and degradation of disordered drugs have seldom received deep attention. Previous investigations from our lab have explored some of these interplays, aiming to develop predictive stability models. As a follow-up, the implication of crystal disorder on the oxidative instability of Olanzapine (OLA) during accelerated storage is investigated in this work. Cryo-milling OLA at varied time intervals generated different extents of crystal disorder. The milled samples were characterized using calorimetry and infrared (IR) spectroscopy to examine the physical state, while their degradation was evaluated using ultra-performance liquid chromatographic methods. An X-ray amorphous OLA sample was generated by melt-cooling, and used as an amorphous reference. The crystallinity of the cryo-milled samples was quantified using a partial least square regression model based on ATR-FTIR spectroscopic data. The cryo-milled samples were exposed to different accelerated stability conditions along with crystalline (unmilled) and quench cooled (amorphous) samples, serving as controls. At periodic intervals, samples were removed from the stability storage, and analyzed using ATR-FTIR and UPLC methods to quantify the crystallinity- and degradation extents. A positive relation was witnessed between the initial degree of crystallinity and degradation kinetics of the disordered OLA samples during stability storage indicating a strong dependency of degradation on the disorder contents for such disordered solids. The results obtained in this study can potentially explain consequences of inter-batch variations of drugs during stability storage, in addition to enabling de-risking strategies towards eliminating solid drug instabilities in product development.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"599-616"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569091","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":"Structural features of the glassy state and their impact on the solid-state properties of organic molecules in pharmaceutical systems.","authors":"George Zografi, Ann Newman, Evgenyi Shalaev","doi":"10.1016/j.xphs.2024.05.014","DOIUrl":"10.1016/j.xphs.2024.05.014","url":null,"abstract":"<p><p>This paper reviews the structure and properties of amorphous active pharmaceutical ingredients (APIs), including small molecules and proteins, in the glassy state (below the glass transition temperature, T_g). Amorphous materials in the neat state and formulated with excipients as miscible amorphous mixtures are included, and the role of absorbed water in affecting glass structure and stability has also been considered. We defined the term \"structure\" to indicate the way the various molecules in a glass interact with each other and form distinctive molecular arrangements as regions or domains of varying number of molecules, molecular packing, and density. Evidence is presented to suggest that such systems generally exist as heterogeneous structures made up of high-density domains surrounded by a lower density arrangement of molecules, termed the microstructure. It has been shown that the method of preparation and the time frame for handling and storage can give rise to variable glass structures and varying physical properties. Throughout this paper, examples are given of theoretical, computer simulation, and experimental studies which focus on the nature of intermolecular interactions, the size of heterogeneous higher density domains, and the impact of such systems on the relative physical and chemical stability of pharmaceutical systems.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"40-69"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071324","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 and dosing simulations of meropenem in septic critically ill patients with complicated intra-abdominal infection or pneumonia.","authors":"Jingjing Huang, Tong Wu, Ruoming Tan, Yunqi Dai, Yuzhen Qiu, Haiwen Lu, Xiaoli Cao, Jialin Liu, Hongping Qu, Xiaoli Wang","doi":"10.1016/j.xphs.2024.09.011","DOIUrl":"10.1016/j.xphs.2024.09.011","url":null,"abstract":"<p><strong>Objectives: </strong>Meropenem pharmacokinetics (PK) may be altered in septic critically ill patients with complicated intra-abdominal infections (cIAI) and pneumonia. We aimed to evaluate the covariates affecting meropenem PK and the performance of different dosing regimens to optimize the PK/pharmacodynamic target.</p><p><strong>Methods: </strong>Population PK analysis was performed using non-linear mixed-effects modeling. The final model was validated and used to simulate meropenem exposure to assess the probability of attaining the 100 %ƒT_>MIC target.</p><p><strong>Results: </strong>Forty-six and 14 patients were respectively enrolled for PK analysis and external validation. A one-compartment linear model adequately described the data of 226 concentrations. The typical clearance (CL) and volume of distribution (Vd) were 9.69 L/h and 27.4 L, respectively. Septic shock from cIAI (cIASS) and actual body weight were significant covariates for meropenem Vd in addition to the influential covariates of creatinine clearance (CL_CR-CG) and augmented renal clearance for CL. External validation showed the robustness and accuracy of this model. Simulation results proposed continuous infusion (CI) dosing regimens of meropenem against pathogens with MICs ≥ 2 mg/L in patients with cIASS and CL_CR-CG ≥ 60 mL/min.</p><p><strong>Conclusions: </strong>For the patients with cIASS and CL_CR-CG ≥ 60 mL/min, CI meropenem is proposed for treatment of less sensitive pathogens with MICs ≥ 2 mg/L.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"269-278"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307978","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":"Proof of a LOD prediction model with orthogonal PAT methods in continuous wet granulation and drying.","authors":"Katharina Kiricenko, Stefan Klinken, Peter Kleinebudde","doi":"10.1016/j.xphs.2024.07.008","DOIUrl":"10.1016/j.xphs.2024.07.008","url":null,"abstract":"<p><p>Real-time monitoring of critical quality attributes, such as residual water in granules after drying which can be determined through loss-on-drying (LOD), during wet granulation and drying is essential in continuous manufacturing. Near-infrared (NIR) spectroscopy has been widely used as process analytical technology (PAT) for in-line LOD monitoring. This study aims to develop and apply a model for predicting the LOD based on process parameters. Additionally, the efficacy of an orthogonal PAT approach using NIR and mass balance (MB) for a vibrating fluidized bed dryer (VFBD) is demonstrated. An in-house-built, cost-effective NIR sensor was utilized for measurements and exhibited good correlation compared to standard method via infrared drying. The combination of NIR and MB, as independent methods, has demonstrated their applicability. A good correlation, with a Pearson r above 0.99, was observed for LOD up to 16 % (w/w). The use of an orthogonal PAT method mitigated the risk of false process adaption. In some experiments where the NIR sensor might have been covered by powder and therefore did not measure accurately, LOD monitoring via MB remained feasible. The developed model effectively predicted LOD or process parameters, resulting in an R2 of 0.882 and a RMSE of 0.475 between predicted and measured LOD using the standard method.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"176-184"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616721","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}