Journal of pharmaceutical sciences最新文献_第8页

Microscope-enabled disc dissolution system: Concordance between drug and polymer dissolution from an amorphous solid dispersion disc and visual disc degradation. 显微镜驱动的圆片溶解系统：无定形固体分散盘中药物和聚合物的溶解与目视盘降解之间的一致性。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-23 DOI: 10.1016/j.xphs.2024.10.039

Shuaiqian Men, James E Polli

{"title":"Microscope-enabled disc dissolution system: Concordance between drug and polymer dissolution from an amorphous solid dispersion disc and visual disc degradation.","authors":"Shuaiqian Men, James E Polli","doi":"10.1016/j.xphs.2024.10.039","DOIUrl":"10.1016/j.xphs.2024.10.039","url":null,"abstract":"A microscopic erosion time test was recently described to anticipate amorphous solid dispersion (ASD) drug load dispersibility limit, using 0.5 ml media volume. Studies here build upon this microscope-enabled method but focus on drug and polymer dissolution from an ASD disc, along with imaging. The objective was 1) to design and build a microscope-enabled disc dissolution system (MeDDiS) with a 900 mL dissolution volume and 2) assess the ability of MeDDiS imaging of dissolving discs to provide concordance with measured drug and polymer dissolution profiles. MeDDiS employed a digital microscope to image ASD discs and a one-liter vessel for dissolution. ASD discs containing ritonavir (5-50 % drug load) and PVPVA were fabricated and subjected to in vitro dissolution using MeDDiS, where disc diameter was quantified with time. Ritonavir and PVPVA release were also measured. Results indicate concordance between imaging and dissolution. Both found 25 % drug load to provide high drug and polymer release, but 30 % yielded low release. Quantitatively, MeDDiS images predicted drug and polymer release profiles, both above and below the drug load cliff. Overall, studies here describe a MeDDiS which has promised to anticipate drug and polymer dissolution, via imaging of dissolving discs, above and below the ASD drug load cliff.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502576","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

Delivery of therapeutic RNA by extracellular vesicles derived from Saccharomyces cerevisiae for medicine applications. 利用从酿酒酵母中提取的细胞外囊泡输送治疗用 RNA，并将其应用于医药领域。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-23 DOI: 10.1016/j.xphs.2024.10.035

Meng Yuan, Wenyuan Ma, Bingxin Liu, Xue Zou, Bilian Huang, Xiaoyan Tian, Yu Jin, Nan Zheng, Zhiwei Wu, Yongxiang Wang

{"title":"Delivery of therapeutic RNA by extracellular vesicles derived from Saccharomyces cerevisiae for medicine applications.","authors":"Meng Yuan, Wenyuan Ma, Bingxin Liu, Xue Zou, Bilian Huang, Xiaoyan Tian, Yu Jin, Nan Zheng, Zhiwei Wu, Yongxiang Wang","doi":"10.1016/j.xphs.2024.10.035","DOIUrl":"10.1016/j.xphs.2024.10.035","url":null,"abstract":"Employing small extracellular vesicles (EVs) as drug delivery vehicles presents a plethora of advantages over conventional drug delivery methods, including biological compatibility, engineering versatility for targeted delivery, and biodegradability. Therefore, strategies aimed at amplifying their therapeutic potential involve developing efficient, tissue-specific, and non-immunogenic delivery approaches. Despite rapid advancements in the realm of EVs as drug delivery systems in recent years, the availability of a high-yield, reproducible, and cost-effective source for EVs production and isolation remains a limiting factor for practical application. In this study, we isolated EVs from Saccharomyces cerevisiae (S.c) and loaded them with cargoes such as hsa-miR-143 (an apoptosis-inducing miRNA) or miR-H6 (a miRNA targeting HSV-1). We demonstrated the capability of these EVs to deliver microRNAs or even large mRNA to a variety of cell types. The therapeutic potential of S.c-derived EVs (S.c-EVs) was further evidenced by their ability to inhibit tumor growth in animal models. The S.c-EVs proved to be safe and non-immunogenic in vivo. Our results suggest that Saccharomyces cerevisiae represents a cost-effective source of extracellular vesicles, serving as nanocarriers for functional drug delivery in therapeutic applications.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502572","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

Bridging the Gap between in vitro and in vivo Solubility-Permeability Interplay. 弥合体外与体内溶解度-渗透性相互作用之间的差距。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-22 DOI: 10.1016/j.xphs.2024.10.008

Michinori Oikawa, Satoru Matsuura, Takeyuki Okudaira, Ryo Ito, Kanako Arima, Masahiro Fushimi, Takamasa Oda, Kaoru Ohyama, Kohsaku Kawakami

{"title":"Bridging the Gap between in vitro and in vivo Solubility-Permeability Interplay.","authors":"Michinori Oikawa, Satoru Matsuura, Takeyuki Okudaira, Ryo Ito, Kanako Arima, Masahiro Fushimi, Takamasa Oda, Kaoru Ohyama, Kohsaku Kawakami","doi":"10.1016/j.xphs.2024.10.008","DOIUrl":"https://doi.org/10.1016/j.xphs.2024.10.008","url":null,"abstract":"Use of solubilization carriers for poorly soluble drugs may disturb transmembrane absorption by lowering the activity of drug molecules, which is known as the solubility-permeability interplay. However, although many in vitro studies have indicated the negative impacts of use of solubilization carriers for oral absorption, in vivo studies that showed the interplay effect are limited. This study provides systematic in vitro, in situ, and in vivo investigation of the interplay effect of cyclodextrin using dexamethasone as a model drug. The evaluation methods included permeation through polymeric, artificial lipid, cell, and intestinal closed-loop membranes. Then, the results were compared with oral administration studies in mice and dogs. Although the interplay effect was clearly observed in the in vitro studies, no obvious interplay was found in the in vivo studies, suggesting that the interplay effect is more prominent in the in vitro permeation studies. Absence of in vivo interplay was attributed to the dilution effect in the gastrointestinal tract, interaction of the drug with living components, and clearance of the drug after membrane permeation. Overall, this investigation clearly demonstrated the applicability and limitations of in vitro permeation studies for predicting the interplay effects of solubilizers after the oral administration.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502570","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

Physical compatibility and chemical stability of bupivacaine, epinephrine, and nalbuphine in 0.45 % sodium chloride, 0.9 % sodium chloride, or plasma-lyte A. 布比卡因、肾上腺素和纳布啡在 0.45%氯化钠、0.9%氯化钠或血浆-Lyte A 中的物理兼容性和化学稳定性。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-18 DOI: 10.1016/j.xphs.2024.10.003

Zachary Senger, Gladys Uwera Mihigo, Mitchell S Howard, Gabriella Baki, Mariann D Churchwell, Virender Kumar, Justin P Reinert

{"title":"Physical compatibility and chemical stability of bupivacaine, epinephrine, and nalbuphine in 0.45 % sodium chloride, 0.9 % sodium chloride, or plasma-lyte A.","authors":"Zachary Senger, Gladys Uwera Mihigo, Mitchell S Howard, Gabriella Baki, Mariann D Churchwell, Virender Kumar, Justin P Reinert","doi":"10.1016/j.xphs.2024.10.003","DOIUrl":"10.1016/j.xphs.2024.10.003","url":null,"abstract":"Purpose: To evaluate the physical compatibility and chemical stability of the combination of bupivacaine, epinephrine, and nalbuphine when in mixed in 0.45 % sodium chloride, 0.9 % sodium chloride, or Plasma-Lyte A.Methods: Bupivacaine 0.5 % (15 mL), epinephrine 1 mg/mL (0.15 mL), and nalbuphine 10 mg/mL (0.5 mL) were combined to prepare three distinct admixtures with 0.45 % sodium chloride, 0.9 % sodium chloride, or Plasma-Lyte A. Visual inspection, spectrophotometric analysis, pH evaluation, and high-performance liquid chromatography tests were conducted at hours 0, 1, 5, 8, and 24. Samples were stored in ambient room light at room temperature.Results: There were no demonstrable changes identified in any of the samples with regards to visual changes, spectrophotometric absorbance, or pH. In each studied fluid, the remaining drug concentrations were an average of 100.92 % bupivacaine, 95.8 % epinephrine, and 100.02 % nalbuphine.Conclusions: The combination of bupivacaine, epinephrine, and nalbuphine was found to be physically compatibility and chemically stable for a period of 24 h at room temperature.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468296","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

Scale-up and clinical bioavailability assessment of a 45 % drug loaded amorphous nanoparticle formulation of a BCS IV compound for oral delivery. 口服给药 BCS IV 化合物的 45% 药物负载无定形纳米粒子制剂的放大和临床生物利用度评估。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-18 DOI: 10.1016/j.xphs.2024.10.014

Mengqi Yu, Deliang Zhou, Hardeep S Oberoi, Ahmed Hamed Salem, Laura A McKee, Jason R Arnholt, Hitesh S Purohit, Devalina Law

{"title":"Scale-up and clinical bioavailability assessment of a 45 % drug loaded amorphous nanoparticle formulation of a BCS IV compound for oral delivery.","authors":"Mengqi Yu, Deliang Zhou, Hardeep S Oberoi, Ahmed Hamed Salem, Laura A McKee, Jason R Arnholt, Hitesh S Purohit, Devalina Law","doi":"10.1016/j.xphs.2024.10.014","DOIUrl":"10.1016/j.xphs.2024.10.014","url":null,"abstract":"A 45 % drug loaded (DL) amorphous nanoparticle (ANP) formulation for a BCS IV drug demonstrated promising pharmacokinetics in dogs (Purohit, et al., J. Pharm. Sci. 2023(113)1007-1019). This preclinical data enabled a human proof-of-concept assessment opportunity. The ANP freeze dried powder for oral suspension was prepared using solvent/antisolvent precipitation followed by organic solvent removal and freeze drying (FD). Challenges manifested during scale-up from 50 g to 280 g. Given the preclinical data, formulation change was restricted, therefore, process modifications were implemented. Cold collection after precipitation prevented particle growth but resulted in 75 nm particles at clinical scale (CS), compared to 150 nm at laboratory scale (LS). This size decrease rendered stabilizer amounts suboptimal for FD operation. Consequently, when FD powder was resuspended in water a smaller fraction of particles was below 450 nm (by filtration), ∼65 % for CS compared to ∼85 % for LS. Formulation was stable for > 6 months, evaluated by monitoring moisture content, assay, powder X-ray diffraction (PXRD), and redispersion time. Despite ∼65 % re-dispersibility, this 45 % DL formulation in humans had higher Cmax and AUC ∼73 % and ∼46 % respectively in fasted-state, and under fed-state it met bioequivalence criteria for AUC but Cmax was 20 % lower compared to reference (10 % DL ASD tablets) demonstrating advantage of ANP strategy over ASD approach.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468298","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

Impact of drug incorporation into micelle on reduced griseofulvin and meloxicam permeation across a hollow fiber membrane. 药物加入胶束对降低格列齐芬和美洛昔康在中空纤维膜上的渗透率的影响

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-18 DOI: 10.1016/j.xphs.2024.10.017

Roshni P Patel, Lynne S Taylor, James E Polli

{"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":"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.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-10-18","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}

引用次数: 0

Simultaneous XRD-DSC identifies correct drug-polymer solubility and miscibility for enantiotropic solid forms. 同时 XRD-DSC 确定药物-聚合物的正确溶解度和各向异性固体形式的混溶性。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-18 DOI: 10.1016/j.xphs.2024.10.018

Mustafa Bookwala, Jiawanjun Shi, Ira S Buckner, Simon Bates, Peter L D Wildfong

{"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":"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 (Tend) 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 Tend 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.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-10-18","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}

引用次数: 0

Evaluation of the impact of the polymer end groups and molecular weight on in vitro and in vivo performances of PLGA based in situ forming implants for ketoprofen. 评估聚合物端基和分子量对基于 PLGA 的酮洛芬原位成型植入物的体外和体内性能的影响。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-18 DOI: 10.1016/j.xphs.2024.10.019

Sanjib Saha, Xinhao Lin, Liping Zhou, Aixiang Xue, Eric Gosselin, Paresh P Chothe, Mittal Darji, Xiuling Lu, Wenzhan Yang

{"title":"Evaluation of the impact of the polymer end groups and molecular weight on in vitro and in vivo performances of PLGA based in situ forming implants for ketoprofen.","authors":"Sanjib Saha, Xinhao Lin, Liping Zhou, Aixiang Xue, Eric Gosselin, Paresh P Chothe, Mittal Darji, Xiuling Lu, Wenzhan Yang","doi":"10.1016/j.xphs.2024.10.019","DOIUrl":"10.1016/j.xphs.2024.10.019","url":null,"abstract":"In situ forming implants are appealing long-acting dosage forms for both preclinical and clinical applications due to their simple manufacturing process and easy delivery. This study aims to develop extended-release in situ forming solid implants for subcutaneous administration using two types of commercially available triblock poly (lactic-co-glycolic acid)-poly (ethylene glycol)-poly (lactic-co-glycolic acid) (PLGA-PEG-PLGA) polymers, with either an acid or ester end group. Both types of polymers instantly form in situ implants when injected directly into an aqueous medium. The performance of these implants, containing a model compound ketoprofen, was evaluated by comparing the in vitro drug release profiles with the in vivo performance following subcutaneous administration in rats. Analytical characterizations of two representative in situ implants were conducted to understand their structural impact on polymer degradation and drug release. All tested in situ forming implants demonstrated prolonged drug release profiles both in vitro and in vivo. This study illustrates the successful preparation of sustained-release in situ forming implant formulations for ketoprofen using commercially available polymers, with the molecular weight and the end group of the polymers affecting their degradation and the drug release from the in situ formed implants.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468290","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

Professor Lynne S. Taylor: Scientist, educator, and adventurer. 林恩-泰勒教授：科学家、教育家和探险家。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-18 DOI: 10.1016/j.xphs.2024.10.015

Dana E Moseson, Na Li, Jukka Rantanen, Keisuke Ueda, Geoff G Z Zhang

引用次数: 0

Mechanisms of drug release from a melt-milled, poorly soluble drug substance. 熔融研磨的难溶性药物释放机制

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-17 DOI: 10.1016/j.xphs.2024.10.016

Dominik Sleziona, David R Ely, Markus Thommes

引用次数: 0