Journal of pharmaceutical sciences最新文献

{"title":"OVERCOMING BARRIERS IN MENKES DISEASE: A STANDARDIZED HIGH QUALITY AND STABLE INJECTABLE COPPER HISTIDINATE.","authors":"María Laura Guzmán, Fiamma Barbieri, Laura Carolina Luciani-Giacobbe, Claudia Marcela Inga, Carolina Bustos Fierro, María Emilia Gavelli, Ana Lidia Apas, Fabiana Del Luján Alovero, Ana María Gasparotto, María Eugenia Olivera","doi":"10.1016/j.xphs.2025.103722","DOIUrl":"https://doi.org/10.1016/j.xphs.2025.103722","url":null,"abstract":"<p><p>Copper histidinate injection, utilized for Menkes disease treatment, suffers from chemical instability and the absence of validated quality control methods. This study aims to develop an optimized stability formulation of copper histidinate and to evaluate its chemical stability using validated methods, supported by microbiological and elemental impurity risk assessment. The original formulation was modified by altering the stoichiometric ratio of histidine to copper from 1:2 to 1:3 (Cu-Hi_inj 1:3). The results indicated a significantly enhanced stability for Cu-Hi_inj 1:3, maintaining copper integrity under all tested conditions, unlike Cu-Hi_inj 1:2, which exhibited notable copper degradation at temperatures above 8°C. The new formulation displayed no degradation except at 60°C, rendering the calculation of validity period (t₉₀) unfeasible. This significantly enhanced stability is attributed to the increased histidine content in Cu-Hi_inj 1:3, which augments the chelating capacity of the copper-histidine complex. Additionally, two validated analytical methods, namely flame atomic absorption spectrometry and redox titration (the latter being an accessible analytical method for compounding pharmacies), demonstrated precision and accuracy for copper quantification, with negligible matrix effects. Sterility tests confirmed the absence of microbial growth, validating the aseptic manufacturing process. This study extends and optimizes the manufacturing procedure by incorporating active principles as salts or neutral substances and accommodating a broader pH range. The Cu-Hi_inj 1:3 formulation not only offers enhanced stability but also shows potential for industrial production, thus improving access to Menkes disease treatment while ensuring safety and efficacy.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"103722"},"PeriodicalIF":3.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624609","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":"Efficient evaluation of the precision of quantitative chromatographic analysis of soft capsules using a chemometric tool","authors":"Ai Sano ,&nbsp;Akira Kotani ,&nbsp;Hideki Hakamata ,&nbsp;Masato Takahashi","doi":"10.1016/j.xphs.2025.103714","DOIUrl":"10.1016/j.xphs.2025.103714","url":null,"abstract":"<div><div>Soft capsules may enhance oral absorption and bioavailability of active substances by appropriately combining them with excipients such as lipids and surfactants. However, these excipients affect the determination of active substances and warrant several considerations for establishing optimal analytical methods. The function of mutual information (FUMI) theory is a chemometric tool that estimates the relative standard deviation (RSD) of the peak area by approximating the baseline of a chromatogram with a stochastic process. In this study, we used a dutasteride (DUT) soft capsule as the specimen, and we propose a method to evaluate the RSD of the peak area of active substances in soft capsules based on the FUMI theory. Furthermore, we have established a method to evaluate the RSD of the peak area using a manual method for signal–noise resolution for soft capsules where the excipients interfere with the active substances. RSD (<em>N</em> = 1) obtained using this method was within the 95 % confidence interval of the RSD estimated using repetitive measurements (<em>N</em> = 6). In conclusion, the proposed method enables the efficient evaluation of precision without requiring repetitive measurements.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 5","pages":"Article 103714"},"PeriodicalIF":3.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In-situ forming solvent-induced phase inversion (SIPI) implants for controlled drug delivery: Role of hydrophilic polymers","authors":"Lalitkumar K. Vora,&nbsp;Hannah McMillian,&nbsp;Deepakkumar Mishra,&nbsp;David Jones,&nbsp;Raghu Raj Singh Thakur","doi":"10.1016/j.xphs.2025.103717","DOIUrl":"10.1016/j.xphs.2025.103717","url":null,"abstract":"<div><div>In recent years, there has been a surge of research focused on in situ-forming implants as a method of localized drug delivery. Despite advancements, the predominant challenge in situ-forming solvent-induced phase inversion (SIPI) implants is significant burst release which typically occurs within the first 24 h post-administration. Another notable challenge is the real-time characterization of these implants, which is crucial for understanding their in situ formation and degradation mechanism. This study explores the impact of various hydrophilic polymers—hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), Carbopol, and carboxymethylcellulose (CMC) - on implant formation and drug release. SIPI systems, which are commonly composed of poly(lactic-co-glycolic acid) (PLGA) and N-methyl pyrrolidone (NMP), offer localized, controlled drug release but suffer from an initial burst within 24 h post-administration. The incorporation of hydrophilic polymers aims to modulate this release and improve implant properties. For first-time, optical coherence tomography (OCT) imaging was employed for non-invasive assessment of the rate of in situ phase inversion and the resulting implant morphology, whereas scanning electron microscopy (SEM) and digital microscopy provided further insights into the internal structure of the implants. The results demonstrated that the inclusion of polymers such as HPMC and Carbopol effectively reduced burst release, whereas polymers such as HPC and CMC exhibited faster phase inversion, resulting in a more porous implant morphology and greater burst release. Additionally, the mechanical properties and mucoadhesive capabilities of the formulations were tested, suggesting that Carbopol-enhanced implants are particularly suitable for applications requiring prolonged retention at mucosal sites. This investigation provides critical insights into the design and optimization of SIPI systems for drug delivery.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 5","pages":"Article 103717"},"PeriodicalIF":3.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the antidiabetic effect of various therapeutic essential oils synergistically with repaglinide","authors":"Omnia M. Sarhan ,&nbsp;Samaa O. Abdelqader ,&nbsp;Mostafa S.A. Mostafa ,&nbsp;Manar A.E. Badawi ,&nbsp;Mohamed A.M. Ahmed ,&nbsp;Waleed G.A. El Sayed ,&nbsp;Mostafa I. Gebril","doi":"10.1016/j.xphs.2025.103721","DOIUrl":"10.1016/j.xphs.2025.103721","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to evaluate the antidiabetic efficacy of microemulsions formulated with cardamom oil, black seed oil, and olive oil. The goal was to determine the optimal formulation for stable microemulsions and assess their potential as innovative drug delivery systems for the antidiabetic drug repaglinide.</div></div><div><h3>Methods</h3><div>Initial phase diagrams were constructed to identify the optimal ratios of oil, water, surfactant (Tween 80), and cosurfactant (ethanol) for producing stable microemulsions. The physical attributes of the resulting formulations, such as droplet size, zeta potential, and morphology, were characterized using transmission electron microscopy. Drug release profiles of microemulsions containing repaglinide were evaluated using the dialysis method. Moreover, vivo studies were conducted to assess the therapeutic efficacy of cardamom oil microemulsions compared to standard commercial repaglinide formulations.</div></div><div><h3>Results</h3><div>Microemulsions exhibited suitable properties with optimal particle size, well-defined spherical droplets, and optimized zeta potential. Drug release studies indicated that cardamom oil-based microemulsions demonstrated superior release characteristics, providing a more sustained and controlled release of repaglinide compared to microemulsions containing black seed or olive oil. In vivo studies revealed a significant improvement in antidiabetic outcomes with cardamom oil microemulsions over standard commercial repaglinide formulations. The enhanced efficacy was attributed to improved bioavailability and the controlled release properties of the drug.</div></div><div><h3>Conclusion</h3><div>This research underscores the potential of cardamom oil-based microemulsions as effective antidiabetic drug delivery systems. With superior physicochemical properties and controlled release profiles, they promise innovative treatment options for diabetes, potentially improving therapeutic outcomes for patients.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 5","pages":"Article 103721"},"PeriodicalIF":3.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586099","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":"Ezetimibe alters micelle structure and reduces Niemann-Pick C1-like 1-mediated absorption of vitamins E and K1 in CaCo-2 cells","authors":"Hideki Aizawa","doi":"10.1016/j.xphs.2025.103712","DOIUrl":"10.1016/j.xphs.2025.103712","url":null,"abstract":"<div><div>Ezetimibe (EZE) is known to inhibit cholesterol absorption by targeting Niemann-Pick C1-like 1 (NPC1L1). However, its effects on the absorption of fat-soluble vitamins, such as Vitamin E and Vitamin K₁, remain unclear. This study investigates how EZE impacts micellar properties and vitamin absorption. We analyzed the shape, size, diffusion rate, and zeta-potential of micelles during Vitamin E and K₁ absorption. Our findings demonstrate that EZE causes micelles to transition from an elliptical to a cylindrical shape, reducing vitamin absorption efficiency. EZE also impairs absorption by altering micelle composition, hindering NPC1L1 binding, and directly blocking vitamin uptake. EZE negatively affects Vitamin E and K₁ absorption, raising concerns about potential deficiencies with long-term use. These findings highlight the need for strategies to minimize the adverse effects of EZE in clinical practice.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 5","pages":"Article 103712"},"PeriodicalIF":3.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586101","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":"Microfluidic development of liposome nanoparticles encapsulated with yam polysaccharide.","authors":"Yuehan Cui, Meng Song, Ruilai Liu, Zhenhao Xi, Ling Zhao, Lian Cen","doi":"10.1016/j.xphs.2025.103718","DOIUrl":"10.1016/j.xphs.2025.103718","url":null,"abstract":"<p><p>A novel liposome nanoparticle loaded with yam polysaccharide was developed in this study via a tailor-made microfluidic device and further optimized through the Box-Behnken Design method of surface analysis to exploit combinational immunomodulatory effects of liposomes and yam polysaccharide. A chip of 100 μm in height and 200 μm in width with a mixing channel with embedded baffles to enhance fluid mixing was first designed and fabricated. Liposome nanoparticles were obtained by manipulating the operating parameters of the microfluidic chip. The formulation of yam polysaccharide loaded liposomes (YPL¹) was optimized using response-surface analysis, and their physicochemical properties were characterized. In vitro cellular assays were performed to assess the effect of YPL on the activity of mouse dendritic cells (DC) and the secretion of immune-related cytokines to investigate the immune-enhancing effect of YPL in vitro. The resulting YPL had a mean size of 154.2±3.8 nm with a narrow size distribution (PDI=0.083) and had a high entrapment efficiency (EE) of 79.02 %. The YPL exhibited good stability at 4 °C over 14 days of storage, and an in vitro sustained release duration of approximately 30 h. The YPL demonstrated excellent biocompatibility and stimulated the expression of immune-related cytokines, especially TNF-α. Therefore, the YPL with well controlled particle size and high loading capacity, capable of exhibiting potent immunostimulatory activity was successfully developed in this study via a microfluidic device and optimized using response-surface analysis. The current YPL engineering methodology could further serve as an experimental platform for liposome nanoparticle development.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"103718"},"PeriodicalIF":3.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586105","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 modeling of methylprednisolone pharmacokinetics across species with extrapolations to humans","authors":"Ruihong Yu,&nbsp;William J. Jusko","doi":"10.1016/j.xphs.2025.103719","DOIUrl":"10.1016/j.xphs.2025.103719","url":null,"abstract":"<div><div>Methylprednisolone (MPL) is widely used in clinical and veterinary medicine to manage inflammation. Plasma profiles and PK parameters in 7 species were digitized from 10 literature sources along with our recent PBPK results in rats. Basic allometric scaling provided reported clearance (<em>CL</em>) and distribution volume (<em>V_d</em>) from noncompartmental analysis highly correlated with body weights (R² &gt; 0.96), although rat <em>CL</em> deviated from the linear trend. A basic nonlinear minimal physiologically-based pharmacokinetic model (mPBPK) (Model I), an intermediate reversible-metabolism mPBPK model (Model II) accounting for MPL and methylprednisone interconversion, and a full highly complex PBPK model were used to assess the interspecies plasma concentration datasets. The MPL PK profiles were reasonably captured by Model I and II, yielding allometric exponents for <em>CL</em> of 1.15 and 0.94, consistent with basic allometry, 1.18. Rat PK informed the presence of nonlinear tissue binding and required an adjustment factor approximately 8-fold higher for its <em>CL</em>. Our full PBPK model was extrapolated from rats to humans using allometry from Model II and optimized producing excellent applications in healthy subjects and patients. This study, based on conserved tissue binding properties, provided three allometric translational PBPK models for MPL, facilitating reasonable PK assessment and interpretation for various species.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 5","pages":"Article 103719"},"PeriodicalIF":3.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586108","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":"AI-enhanced X-ray microscopy for non-destructive detection, quantification, and particle size analysis of crystalline miconazole in amorphous solid dispersions","authors":"Yongan Tang ,&nbsp;Isha Bordawekar ,&nbsp;Adam J. Zaczek ,&nbsp;Andrew D. Vogt","doi":"10.1016/j.xphs.2025.103720","DOIUrl":"10.1016/j.xphs.2025.103720","url":null,"abstract":"<div><div>In the pharmaceutical industry, amorphous solid dispersions (ASDs) are commonly utilized to enhance the solubility and bioavailability of poorly soluble active pharmaceutical ingredients (APIs). Polymers such as copovidone are also frequently employed as stabilizing agents in ASDs due to their ability to reduce the thermodynamical instability of the amorphous form compared to their crystalline form. Detecting and measuring any crystalline API particles present in the ASD formulation is critical for ensuring drug efficacy and stability. In this study, ASD tablets miconazole in a copovidone matrix spiked with known concentration of crystalline miconazole were characterized by X-ray microscopy (XRM). We demonstrate how XRM combined with AI-assisted image segmentation can provide quantitative characterization of crystalline particles, including detailed particle size distribution (PSD) information. The AI-assisted image processing model was found to be robust, reducing human error associated with traditional threshold selection. Additionally, we evaluated particle size changes from the blend to the final drug product to understand how the API and excipient behave during tablet manufacturing. This approach has broader applications in drug product development, particularly in monitoring recrystallization and evaluating process-induced changes during blending and compression.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 5","pages":"Article 103720"},"PeriodicalIF":3.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573325","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":"Transportation of protein drugs at hospital: Comparison of mechanical stress occurring during pneumatic transportation and hand-carried transport.","authors":"Pauline Barreau, Fréderic Feutry, Marie Abelé, Alexandre Villain, Ilyes Sakji, Guillaume Marliot","doi":"10.1016/j.xphs.2025.103715","DOIUrl":"10.1016/j.xphs.2025.103715","url":null,"abstract":"<p><p>In this study, we quantitatively characterize the mechanical shock generated in the pneumatic transport systems (PTS) in our center, determine the PTS pipeline with the highest risk of mechanical stress, and compare these results with hand-carried transport by trolleys or transportation boxes. Acceleration measurements were performed in triplicate for each of the five departments using a 3-axis accelerometer, which was fixed to three distinct experimental bags and a syringe. We measured the area under the curve (AUC) of the acceleration distribution with a threshold of 2 g, and the number of acceleration peaks (NAP) from >3 to 15 g-forces. The data obtained were calculated using bilateral Wilcoxon-Mann-Whitney non-parametric tests. The AUC and NAP_3-15 g-forces for PTS were significantly greater than those for hand-carried transport by trolley and box (p < 0.001), which did not show any peak above the NAP₁₀. The PTS pipeline with more curves and redirection airlocks had the highest risk of mechanical stress, whereas no difference was observed per type of container. Transport by trolley had significantly greater (p < 0.001) AUC, NAP₃, and NAP₅ than by box. Our results indicate that there is greater mechanical stress arising during PTS transportation than during hand-carried transport, preferentially in transportation boxes.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"103715"},"PeriodicalIF":3.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573343","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":"Corrigendum to “Review on 505(b)(2) Drug products approved by USFDA from 2010 to 2020 emphasizing intellectual property and regulatory considerations for reformulations and new combinations” [Journal of Pharmaceutical Sciences/ Volume 112, Issue 8, August 2023/ Pages 2146-2175]","authors":"Jyosna Devi Ravula ,&nbsp;Ramakrishna Nirogi ,&nbsp;Manthan D. Janodia","doi":"10.1016/j.xphs.2025.103716","DOIUrl":"10.1016/j.xphs.2025.103716","url":null,"abstract":"","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 4","pages":"Article 103716"},"PeriodicalIF":3.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573333","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}