European Journal of Pharmaceutics and Biopharmaceutics最新文献

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Dissolving microneedle patches for delivery of amniotic mesenchymal stem cell metabolite products for skin regeneration in UV-aging induced mice 用于输送羊膜间充质干细胞代谢物产品的可溶解微针贴片,促进紫外线老化诱导小鼠的皮肤再生
IF 4.4 2区 医学
European Journal of Pharmaceutics and Biopharmaceutics Pub Date : 2024-09-13 DOI: 10.1016/j.ejpb.2024.114482
{"title":"Dissolving microneedle patches for delivery of amniotic mesenchymal stem cell metabolite products for skin regeneration in UV-aging induced mice","authors":"","doi":"10.1016/j.ejpb.2024.114482","DOIUrl":"10.1016/j.ejpb.2024.114482","url":null,"abstract":"<div><p>Microneedles offer a promising solution to enhancing dermal delivery of amniotic mesenchymal stem cell metabolite product (AMSC-MP), which contains hydrophilic protein components with high molecular weight, for the purposes of skin rejuvenation and improving human health. This study aimed to evaluate the physicochemical characteristics and in vivo efficacy of AMSC-MP-loaded microneedle patches for effectively regenerating skin tissues in UV-aging induced mice. Dissolving microneedle patches, composed of polyvinyl alcohol with an MW of 9–10 kDa and polyvinylpyrrolidone with an MW of 56 kDa, were fabricated using the double-casting method at three AMSC-MP concentrations: i.e., 30 % (MN30), 25 % (MN25), and 20 % (MN20). The microneedles patches were then evaluated for morphological, mechanical resistance, and insertion properties. An ex vivo release study was also conducted using the Franz cell method, and in vivo efficacy and irritation were then determined through collagen density scores, fibroblast cell counts, and skin irritation studies of UV-aging induced mice. The AMSC-MP microneedles displayed a pyramidal shape with 500 µm sharp tips. Mechanical testing revealed that MN30 achieved its deepest insertion into Parafilm® M (447.44 ± 37.21 µm), while MN25 achieved its deepest insertion into full-thickness porcine skin (717.92 ± 25.40 µm). The study revealed a controlled EGF release for up to 24 h, with MN20 exhibiting the highest deposition (55.94 ± 12.34 %). These findings demonstrate the successful penetration of microneedles through the stratum corneum and viable epidermis. Collagen density scores and fibroblast cell counts were significantly higher in all microneedle formulations than the control, with MN30 having the highest values. Inflammatory cell counts indicated minimal presence suggesting non-irritation in the in vivo study. Dissolving microneedle patches exhibited favorable characteristics and efficiently delivered AMSC-MP with minimal potential for irritation, providing potential technology for delivering biological anti-aging agents for the purposes of fostering skin regeneration.</p></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142232231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 floatability characteristics of gastroretentive tablets using VIS imaging with artificial neural networks 利用人工神经网络 VIS 成像评估胃复安片剂的漂浮特性
IF 4.4 2区 医学
European Journal of Pharmaceutics and Biopharmaceutics Pub Date : 2024-09-11 DOI: 10.1016/j.ejpb.2024.114493
{"title":"Evaluation of floatability characteristics of gastroretentive tablets using VIS imaging with artificial neural networks","authors":"","doi":"10.1016/j.ejpb.2024.114493","DOIUrl":"10.1016/j.ejpb.2024.114493","url":null,"abstract":"<div><p>Gastroretentive dosage forms are recommended for several active substances because it is often necessary for the drug to be released from the carrier system into the stomach over an extended period. Among gastroretentive dosage forms, floating tablets are a very popular pharmaceutical technology. In this study, it was investigated whether a rapid, nondestructive method can be used to characterize the floating properties of a tablet.</p><p>To accomplish our objective, the same composition was compressed, and varied compression forces were applied to achieve the desired tablet. In addition to physical examinations, digital microscopic images of the tablets were captured and analyzed using image analysis techniques, allowing the investigation of the floatability of the dosage form. Image processing algorithms and artificial neural networks (ANNs) were utilized to classify the samples based on their strength and floatability. The input dataset consisted solely of the acquired images.</p><p>It has been shown by our research that visible imaging coupled with pattern recognition neural networks is an efficient way to categorize these samples based on their floatability. Rapid and non-destructive digital imaging of tablet surfaces is facilitated by this method, offering insights into both crushing strength and floating properties.</p></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0939641124003199/pdfft?md5=e38607ae3f7d7580be3bd74f59e4d949&pid=1-s2.0-S0939641124003199-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142228749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Novel long-acting treatment for schizophrenia based on paliperidone dissolving and implantable microarray patches 基于帕潘立酮溶解和植入式微阵列贴片的新型精神分裂症长效疗法
IF 4.4 2区 医学
European Journal of Pharmaceutics and Biopharmaceutics Pub Date : 2024-09-08 DOI: 10.1016/j.ejpb.2024.114481
{"title":"Novel long-acting treatment for schizophrenia based on paliperidone dissolving and implantable microarray patches","authors":"","doi":"10.1016/j.ejpb.2024.114481","DOIUrl":"10.1016/j.ejpb.2024.114481","url":null,"abstract":"<div><p>Schizophrenia is a severe mental disorder that affects millions of people worldwide. Several atypical antipsychotic medications, including paliperidone (PPD), has been developed and proven effective in treating it. To date, four PPD extended-release products have been launched commercially, providing up to six months of therapeutic effect with a single administration. However, the need for hospital injections by professional healthcare workers not only lead to poor patients’ adherence, but also put additional pressure on the healthcare system. Therefore, three PPD microarray patch (PPD MAP) systems based on dissolving microneedle technology and implantable microneedle technology were developed in this work. The two dissolving microarray patch systems contained either PPD crude drug (PPD DMAP-CD) or PPD nanocrystal (PPD DMAP-NC) and the implantable MAP contained PPD crude drug (PPD IMAP). All three types of PPD MAPs showed excellent mechanical and insertion properties as they achieved over 256 µm insertion depth in skin model. <em>In vitro</em> release study showed that PPD released from IMAP in a much more sustained manner (up to 14 days) than PPD did from DMAPs (7 days), with only 20 % initial burst release from IMAP compared with 43–71 % from DMAPs. The MAP dissolution study showed that both DMAPs can be immediately dissolved within less than 3 min once inserted into the skin, indicating a faster action potential compared with IMAP. <em>Ex vivo</em> delivery study showed that 1.68 ± 0.23 mg, 1.39 ± 0.07 mg, and 1.18 ± 0.12 mg were delivered from DMAP-CD, DMAP-NC and IMAP, respectively, demonstrating that over 50 % and up to 70 % of PPD in the MAPs can be delivered into the skin. The IMAP offers most sustained release of PPD whereas DMAP-NC exhibits fastest PPD release (11.19 % vs 20.01 % into Franz cell receiver compartment over 24 h). This work presents a promising alternative for the sustained delivery of antipsychotic drugs, allowing for patient self-administration and extended release concurrently. Patients may potentially use both DMAP and IMAP to achieve a sustained release of PPD while also avoid having an initial therapeutic lag.</p></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0939641124003072/pdfft?md5=875cf926980de69e01972ae85544a448&pid=1-s2.0-S0939641124003072-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142168153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Advances and perspectives in use of semisolid formulations for photodynamic methods
IF 4.4 2区 医学
European Journal of Pharmaceutics and Biopharmaceutics Pub Date : 2024-09-08 DOI: 10.1016/j.ejpb.2024.114485
{"title":"Advances and perspectives in use of semisolid formulations for photodynamic methods","authors":"","doi":"10.1016/j.ejpb.2024.114485","DOIUrl":"10.1016/j.ejpb.2024.114485","url":null,"abstract":"<div><p>Although nearly 30 years have passed since the introduction of the first clinically approved photosensitizer for photodynamic therapy, progress in developing new pharmaceutical formulations remains unsatisfactory. This review highlights that despite years of research, many recurring challenges and issues remain unresolved. The paper includes an analysis of selected essential studies involving aminolevulinic acid and its derivatives, as well as other photosensitizers with potential for development as medical products. Among various possible vehicles, special attention is given to gelatin, alginates, poly(ethylene oxide), polyacrylic acid, and chitosan. The focus is particularly on infectious and cancerous diseases. Key aspects of developing new semi-solid drug forms should prioritize the creation of easily manufacturable and biocompatible preparations for clinical use. At the same time, new formulations should preserve the primary function of photosensitizers, which is the generation of reactive oxygen species capable of destroying pathogenic cells or tumors. Additionally, the use of adjuvant properties of carriers, which can enhance the effectiveness of macrocycles, is emphasized, especially in chitosan-based antibacterial formulations. Current research indicates that many promising dyes and macrocyclic compounds with high potential as photosensitizers in photodynamic therapy remain unexplored in formulation and development work. This review outlines potential new and previously explored pathways for advancing photosensitizers as active pharmaceutical ingredients (APIs).</p></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0939641124003114/pdfft?md5=c72e19980532407062469c8f8726084e&pid=1-s2.0-S0939641124003114-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
In silico evaluation of corneal patch eluting anti-VEGF agents concept 角膜贴片洗脱抗血管内皮生长因子药物概念的硅学评估
IF 4.4 2区 医学
European Journal of Pharmaceutics and Biopharmaceutics Pub Date : 2024-09-08 DOI: 10.1016/j.ejpb.2024.114494
{"title":"In silico evaluation of corneal patch eluting anti-VEGF agents concept","authors":"","doi":"10.1016/j.ejpb.2024.114494","DOIUrl":"10.1016/j.ejpb.2024.114494","url":null,"abstract":"<div><p>This study introduces a novel approach utilizing a temporary drug-eluting hydrogel corneal patch to prevent neovascularization, alongside a numerical predictive tool for assessing the release and transport kinetics of bevacizumab (BVZ) after the keratoplasty. A key focus was investigating the impact of tear film clearance on the release kinetics and drug transport from the designed corneal patch. The proposed tear drug clearance model incorporates the physiological mechanism of lacrimal flow (tear turnover), distinguishing itself from previous models. Validation against experimental data confirms the model’s robustness, despite limitations such as a 2D axisymmetrical framework and omission of blink frequency and saccadic eye movements potential effects. Analysis highlights the significant influence of lacrimal flow on ocular drug transport, with the corneal patch extending BVZ residence time compared to topical administration. This research sets the stage for exploring multi-layer drug-eluting corneal patches as a promising therapeutic strategy in ocular health.</p></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0939641124003205/pdfft?md5=152eccd17f2b0f67ac858428c27b5d96&pid=1-s2.0-S0939641124003205-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142162295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
A small step toward precision dosing of caffeine in preterm infants: An external evaluation of published population pharmacokinetic models 早产儿咖啡因精确剂量的一小步:对已发布的群体药代动力学模型进行外部评估
IF 4.4 2区 医学
European Journal of Pharmaceutics and Biopharmaceutics Pub Date : 2024-09-07 DOI: 10.1016/j.ejpb.2024.114484
{"title":"A small step toward precision dosing of caffeine in preterm infants: An external evaluation of published population pharmacokinetic models","authors":"","doi":"10.1016/j.ejpb.2024.114484","DOIUrl":"10.1016/j.ejpb.2024.114484","url":null,"abstract":"<div><h3>Background</h3><p>Several population pharmacokinetic (PopPK) models of caffeine in preterm infants have been published, but the extrapolation of these models to facilitate model-informed precision dosing (MIPD) in clinical practice is uncertain. This study aimed to comprehensively evaluate their predictive performance using an external<u>,</u> independent dataset.</p></div><div><h3>Methods</h3><p>Data used for external evaluation were based on an independent cohort of preterm infants. Currently available PopPK models for caffeine in preterm infants were identified and re-established. Prediction- and simulation-based diagnostics were used to assess model predictability. The influence of prior information was assessed using Bayesian forecasting.</p></div><div><h3>Results</h3><p>120 plasma samples from 76 preterm infants were included in the evaluation dataset. Twelve PopPK models of caffeine in preterm infants were re-established based on our previously published study. Although two models showed superior predictive performance, none of the 12 PopPK models met all the clinical acceptance criteria of these external evaluation items. Besides, the external predictive performances of most models were unsatisfactory in prediction- and simulation-based diagnostics. Nevertheless, the application of Bayesian forecasting significantly improved the predictive performance, even with only one prior observation.</p></div><div><h3>Conclusions</h3><p>Two models that included the most covariates had the best predictive performance across all external assessments. Inclusion of different covariates, heterogeneity of preterm infant characteristics, and different study designs influenced predictive performance. Thorough evaluation is needed before these PopPK models can be implemented in clinical practice. The implementation of MIPD for caffeine in preterm infants could benefit from the combination of PopPK models and Bayesian forecasting as a helpful tool.</p></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0939641124003102/pdfft?md5=7f1f5dc7b7bf3fb103d4cf84c6de86ef&pid=1-s2.0-S0939641124003102-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142162294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Pediatric oral extemporaneous preparations and practices: International Pharmaceutical Federation (FIP) global study 儿科口服即食制剂和做法:国际制药联合会(FIP)全球研究。
IF 4.4 2区 医学
European Journal of Pharmaceutics and Biopharmaceutics Pub Date : 2024-09-06 DOI: 10.1016/j.ejpb.2024.114483
{"title":"Pediatric oral extemporaneous preparations and practices: International Pharmaceutical Federation (FIP) global study","authors":"","doi":"10.1016/j.ejpb.2024.114483","DOIUrl":"10.1016/j.ejpb.2024.114483","url":null,"abstract":"<div><p>This publication is the first to report current, global, pediatric oral extemporaneous compounding practices. Complete survey responses were received from 479 participants actively involved in compounding across all the World Health Organization (WHO) regions. The survey addressed oral formulation of extemporaneous liquids, including the use of commercial or in-house vehicles, flavoring excipients, source of formulation recipes, and beyond use dates (BUDs). Over 90% of the survey participants prepared oral liquids. Solid dosage forms, comprising capsules and powder papers (sachets), were also frequently prepared for children, albeit to a lesser extent. The top 20 active pharmaceutical ingredients compounded for children, globally, were: omeprazole, captopril, spironolactone, propranolol, furosemide, phenobarbital, hydrochlorothiazide, ursodeoxycholic acid, sildenafil, melatonin, clonidine, enalapril, dexamethasone, baclofen, caffeine, chloral hydrate, trimethoprim, atenolol, hydrocortisone, carvedilol and prednisolone. Diuretics, drugs for acid-related disorders, and beta-blockers were the top three most frequently compounded classes per the WHO Anatomical Therapeutic Chemical (ATC) classification system. The principal need identified for the practice of extemporaneous compounding for children was the development of an international, open-access formulary that includes validated formulations, as well as updated compounding literature and guidelines. Furthermore, improved access to data from stability studies to allow compounding of formulations with extended BUDs.</p></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Physiologically based in vitro – in vivo correlation of modified release oral formulations with non-linear intestinal absorption: A case study using mirabegron 基于生理学的体外-体内修正释放口服制剂与非线性肠道吸收的相关性:使用米拉贝琼的案例研究。
IF 4.4 2区 医学
European Journal of Pharmaceutics and Biopharmaceutics Pub Date : 2024-09-02 DOI: 10.1016/j.ejpb.2024.114479
{"title":"Physiologically based in vitro – in vivo correlation of modified release oral formulations with non-linear intestinal absorption: A case study using mirabegron","authors":"","doi":"10.1016/j.ejpb.2024.114479","DOIUrl":"10.1016/j.ejpb.2024.114479","url":null,"abstract":"<div><p>Establishing an <em>in vitro</em> – <em>in vivo</em> correlation (IVIVC) for oral modified release (MR) formulations would make it possible to substitute an <em>in vitro</em> dissolution test for human bioequivalence (BE) studies when changing the formulation or manufacturing methods. However, the number of IVIVC applications and approvals are reportedly low. One of the main reasons for failure to obtain IVIVCs using conventional methodologies may be the lack of consideration of the dissolution and absorption mechanisms of drugs in the physiological environment. In particular, it is difficult to obtain IVIVC using conventional methodologies for drugs with non-linear absorption processes. Therefore, the aim of the present study was to develop a physiologically based biopharmaceutics model (PBBM) that enables Level A IVIVCs for mirabegron MR formulations with non-linear absorption characteristics.</p><p>Using human pharmacokinetic (PK) data for immediate-release formulations of mirabegron, the luminal drug concentration-dependent membrane permeation coefficient was calculated through curve fitting. The membrane permeation coefficient data were then applied to the human PK data of the MR formulations to estimate the <em>in vivo</em> dissolution rate by curve fitting. It was assumed that <em>in vivo</em> dissolution could be described using a zero-order rate equation. Furthermore, a Levy plot was generated using the estimated <em>in vivo</em> dissolution rate and the <em>in vitro</em> dissolution rate obtained from the literature. Finally, the dissolution rate of the MR formulations from the Levy plot was applied to the PBBM to predict the oral PK of the mirabegron MR formulations.</p><p>This PB-IVIVC approach successfully generated linear Levy plots with slopes of almost 1.0 for MR formulations with different dose strengths and dissolution rates. The Cmax values of the MR formulations were accurately predicted using this approach, whereas the prediction errors for AUC exceeded the Level A IVIVC criteria. This can be attributed to the incomplete description of colonic absorption in the current PBBM.</p></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0939641124003059/pdfft?md5=a5f2185c9c11d839d13a2add72eed60f&pid=1-s2.0-S0939641124003059-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
A 3D in-vitro biomimicking Caco-2 intestinal permeability model-based assessment of physically modified telmisartan towards an alkalizer-free formulation development 基于三维体外生物模拟 Caco-2 肠道渗透性模型的物理修饰替米沙坦评估,以开发无碱制剂。
IF 4.4 2区 医学
European Journal of Pharmaceutics and Biopharmaceutics Pub Date : 2024-09-01 DOI: 10.1016/j.ejpb.2024.114480
{"title":"A 3D in-vitro biomimicking Caco-2 intestinal permeability model-based assessment of physically modified telmisartan towards an alkalizer-free formulation development","authors":"","doi":"10.1016/j.ejpb.2024.114480","DOIUrl":"10.1016/j.ejpb.2024.114480","url":null,"abstract":"<div><p>Efficient telmisartan delivery for hypertension management requires the incorporation of meglumine and/or sodium hydroxide as an alkalizer in the formulation. Long-term use of powerful alkalis with formulation as part of chronic therapy can cause metabolic alkalosis, ulcers, diarrhea, and body pain. Here, we aimed to design a telmisartan formulation without alkalizers. Telmisartan properties were tailor-made by microfluidizer-based physical modification. After microfluidization, telmisartan nanosuspension was lyophilized to obtain telmisartan premix powder. The optimized telmisartan nanosuspension had an average particle size of 579.85 ± 32.14 nm. The lyophilized premix was characterized by FT-IR, DSC, and PXRD analysis to ensure its physicochemical characteristics. The solubility analysis of premix showed 2.2 times, 2.3 times, and 6 times solubility improvement in 0.1 N HCl, phosphate buffer pH 7.5, and pH 6.8 compared to pure telmisartan. A 3D <em>in-vitro</em> Caco-2 model was developed to compare apparent permeability of API and powder premix. It showed that the powder premix was more permeable than pure API. The tablet formulation prepared from the telmisartan premix showed a dissolution profile comparable to that of the marketed formulation. The technique present herein can be used as a platform technology for solubility and permeability improvement of similar classes of molecules.</p></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
A unifying approach to drug-in-polymer solubility prediction: Streamlining experimental workflow and analysis 药物在聚合物中溶解度预测的统一方法:简化实验工作流程和分析。
IF 4.4 2区 医学
European Journal of Pharmaceutics and Biopharmaceutics Pub Date : 2024-09-01 DOI: 10.1016/j.ejpb.2024.114478
{"title":"A unifying approach to drug-in-polymer solubility prediction: Streamlining experimental workflow and analysis","authors":"","doi":"10.1016/j.ejpb.2024.114478","DOIUrl":"10.1016/j.ejpb.2024.114478","url":null,"abstract":"<div><p>This method paper describes currently used experimental methods to predict the drug-in-polymer solubility of amorphous solid dispersions and offers a combined approach for applying the <em>Melting-point-depression method</em>, the <em>Recrystallization method</em>, and the <em>Melting-and-mixing method</em>. It aims to describe and expand on the theoretical basis as well as the analytical methodology of the recently published <em>Melting-and-mixing method</em>. This solubility method relies on determining the relationship between drug loads and the enthalpy of melting and mixing of a crystalline drug in the presence of an amorphous polymer. This relationship is used to determine the soluble drug load of an amorphous solid dispersion from the recorded enthalpy of melting and mixing of the crystalline drug portion in a drug-polymer sample at equilibrium solubility. Due to the complex analytical methodology of the <em>Melting-and-mixing method</em>, a software solution called the <em>Glass Solution Companion app</em> was developed. Using this new tool, it is possible to calculate the predicted drug-in-polymer solubility and Flory-Huggins interaction parameter from experimental samples, as well as to generate the resulting solubility-temperature curve. This software can be used for calculations for all three experimental methods, which would be useful for comparing the applicability of the methods on a given drug-polymer system. Since it is difficult to predict the suitability of these drug-in-polymer solubility methods for a specific drug-polymer system <em>in silico</em>, some experimental investigation is necessary. By optimizing the experimental protocol, it is possible to collect data for the three experimental methods simultaneously for a specific drug-polymer system. These results can then be readily analyzed using the <em>Glass Solution Companion app</em> to find the most appropriate method for the drug-polymer system, and therefore, the most reliable drug-in-polymer solubility prediction.</p></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0939641124003047/pdfft?md5=0dc41c456466d07409605e53503dbc86&pid=1-s2.0-S0939641124003047-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
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