首页 > 最新文献

Pharmaceutical Development and Technology最新文献

英文 中文
Pharmaceutical excipients in pediatric and geriatric drug formulations: safety, efficacy, and regulatory perspectives.
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-14 DOI: 10.1080/10837450.2024.2441181
Tansel Comoglu, Emine Dilek Ozyilmaz

Pharmaceutical excipients are indispensable components of drug formulations, playing critical roles in enhancing stability, improving bioavailability, and ensuring patient compliance. In pediatric and geriatric populations, the selection of these excipients becomes even more crucial due to their unique physiological and pharmacokinetic profiles, as well as age-specific formulation requirements. This review examines the functions, safety considerations, and potential adverse effects of excipients in these vulnerable groups. It addresses the challenges of drug formulation for neonates, infants, and elderly patients, including immature enzyme systems, polypharmacy, and swallowing difficulties. The impact of excipient-excipient and excipient-active pharmaceutical ingredient (API) interactions on drug stability, efficacy, and safety is also highlighted. For instance, the effects of polyethylene glycol (PEG) in patients with impaired renal function and destabilizing interactions between surfactants and protein-based APIs are analyzed. Additionally, current guidelines and safety requirements from regulatory bodies such as the FDA, EMA, and ICH are reviewed. This paper emphasizes the importance of carefully selecting excipients that balance functionality and safety to ensure therapeutic efficacy while minimizing risks for pediatric and geriatric patients. Future directions in excipient development and formulation strategies are also discussed to improve treatment outcomes for these populations.

{"title":"Pharmaceutical excipients in pediatric and geriatric drug formulations: safety, efficacy, and regulatory perspectives.","authors":"Tansel Comoglu, Emine Dilek Ozyilmaz","doi":"10.1080/10837450.2024.2441181","DOIUrl":"10.1080/10837450.2024.2441181","url":null,"abstract":"<p><p>Pharmaceutical excipients are indispensable components of drug formulations, playing critical roles in enhancing stability, improving bioavailability, and ensuring patient compliance. In pediatric and geriatric populations, the selection of these excipients becomes even more crucial due to their unique physiological and pharmacokinetic profiles, as well as age-specific formulation requirements. This review examines the functions, safety considerations, and potential adverse effects of excipients in these vulnerable groups. It addresses the challenges of drug formulation for neonates, infants, and elderly patients, including immature enzyme systems, polypharmacy, and swallowing difficulties. The impact of excipient-excipient and excipient-active pharmaceutical ingredient (API) interactions on drug stability, efficacy, and safety is also highlighted. For instance, the effects of polyethylene glycol (PEG) in patients with impaired renal function and destabilizing interactions between surfactants and protein-based APIs are analyzed. Additionally, current guidelines and safety requirements from regulatory bodies such as the FDA, EMA, and ICH are reviewed. This paper emphasizes the importance of carefully selecting excipients that balance functionality and safety to ensure therapeutic efficacy while minimizing risks for pediatric and geriatric patients. Future directions in excipient development and formulation strategies are also discussed to improve treatment outcomes for these populations.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1-9"},"PeriodicalIF":2.6,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Preparation and characterization of poly(ethylene glycol)-b-poly(tert-butyl methacrylate) micelles as potential nanocarriers for donepezil. 作为多奈哌齐潜在纳米载体的聚环氧乙烷-b-聚甲基丙烯酸叔丁酯胶束的制备与表征
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-01 Epub Date: 2024-11-14 DOI: 10.1080/10837450.2024.2423833
Gizem İğdeli, Laura Fritzen, Claus U Pietrzik, Binnur Aydogan Temel

Polymeric micelles were prepared for the delivery of donepezil, a leading Alzheimer's disease drug, to enhance its transport across the blood-brain barrier (BBB). Poly(ethylene glycol)-b-poly(tert-butyl methacrylate) amphiphilic block copolymers were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymers were characterized by gel permeation chromatography and nuclear magnetic resonance spectroscopy. Empty and donepezil loaded polymer micelles were formed using the dialysis method and characterized by dynamic light scattering and transmission electron microscopy. Drug loading efficiency and release behavior were monitored using UV/Vis spectroscopy, and cytotoxicity was evaluated via colorimetric tests and impedance measurements. Additionally, the permeability of the nanocarriers across an in vitro BBB culture model was assessed. Drug-loaded micelles demonstrated similar permeability to free donepezil but offered sustained release and improved stability. This micellar delivery system holds significant potential for improving therapeutic outcomes in Alzheimer's treatment by enhancing donepezil's delivery across the BBB. Improved BBB permeability and sustained drug release could lead to more effective concentration of the drug in the brain, potentially reducing peripheral cholinergic side effects, such as nausea and vomiting, often observed with traditional donepezil administration. This could result in better patient compliance and improved cognitive outcomes, making this nanocarrier system a promising alternative for Alzheimer's therapy.

制备了用于递送阿尔茨海默病(AD)主要药物多奈哌齐的聚合物胶束,以增强其通过血脑屏障(BBB)的运输。通过可逆加成-断裂链转移(RAFT)聚合法合成了聚乙二醇-b-聚甲基丙烯酸叔丁酯两亲嵌段共聚物。凝胶渗透色谱(GPC)和核磁共振(NMR)光谱对聚合物进行了表征。利用透析法形成了空胶束和多奈哌齐负载聚合物胶束,并通过动态光散射(DLS)和透射电子显微镜(TEM)对其进行了表征。利用紫外/可见光谱监测了药物负载效率和释放行为,并通过比色测试和阻抗测量评估了细胞毒性。此外,还评估了纳米载体在体外 BBB 培养模型中的渗透性。载药胶束的渗透性与游离多奈哌齐相似,但具有持续释放和更高的稳定性。这种胶束递送系统通过增强多奈哌齐在生物BB中的递送,在改善阿尔茨海默氏症的治疗效果方面具有巨大潜力。改善多奈哌齐的 BBB 通透性和持续药物释放可提高药物在大脑中的有效浓度,从而有可能减少传统多奈哌齐用药经常出现的外周胆碱能副作用,如恶心和呕吐。这可能会提高患者的依从性并改善认知结果,使这种纳米载体系统成为阿尔茨海默氏症治疗的一种有前途的替代疗法。
{"title":"Preparation and characterization of poly(ethylene glycol)-<i>b</i>-poly(<i>tert</i>-butyl methacrylate) micelles as potential nanocarriers for donepezil.","authors":"Gizem İğdeli, Laura Fritzen, Claus U Pietrzik, Binnur Aydogan Temel","doi":"10.1080/10837450.2024.2423833","DOIUrl":"10.1080/10837450.2024.2423833","url":null,"abstract":"<p><p>Polymeric micelles were prepared for the delivery of donepezil, a leading Alzheimer's disease drug, to enhance its transport across the blood-brain barrier (BBB). Poly(ethylene glycol)-<i>b</i>-poly(<i>tert</i>-butyl methacrylate) amphiphilic block copolymers were synthesized <i>via</i> reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymers were characterized by gel permeation chromatography and nuclear magnetic resonance spectroscopy. Empty and donepezil loaded polymer micelles were formed using the dialysis method and characterized by dynamic light scattering and transmission electron microscopy. Drug loading efficiency and release behavior were monitored using UV/Vis spectroscopy, and cytotoxicity was evaluated <i>via</i> colorimetric tests and impedance measurements. Additionally, the permeability of the nanocarriers across an <i>in vitro</i> BBB culture model was assessed. Drug-loaded micelles demonstrated similar permeability to free donepezil but offered sustained release and improved stability. This micellar delivery system holds significant potential for improving therapeutic outcomes in Alzheimer's treatment by enhancing donepezil's delivery across the BBB. Improved BBB permeability and sustained drug release could lead to more effective concentration of the drug in the brain, potentially reducing peripheral cholinergic side effects, such as nausea and vomiting, often observed with traditional donepezil administration. This could result in better patient compliance and improved cognitive outcomes, making this nanocarrier system a promising alternative for Alzheimer's therapy.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1111-1120"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Applications of therapeutic deep eutectic solvents (THEDESs) as antimicrobial and anticancer agents. 治疗性深共晶溶剂(THEDESs)作为抗菌剂和抗癌剂的应用。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-01 Epub Date: 2024-11-04 DOI: 10.1080/10837450.2024.2421786
Hala Bakr El-Nassan

Deep eutectic solvents (DESs) are green alternatives to ionic liquids with wide applications in organic synthesis and catalysis. DESs are characterized by being easily prepared, biodegradable, nontoxic, and noninflammable. When one or more of the DES components is active pharmaceutical ingredient (API), the eutectic mixtures are named as therapeutic deep eutectic solvents (THEDESs). THEDESs are prepared in order to improve the solubility and/or the permeability of the APIs. This review presents a brief summary of the most important THEDESs reported to date having antimicrobial and/or anticancer activities. The challenges and limitations of THEDES preparation were also discussed. The work presented here indicated the importance of THEDES as a promising drug delivery system that can overcome the bioavailability problems while retaining or enhancing the biological activity of its components.

深共晶溶剂(DES)是离子液体的绿色替代品,在有机合成和催化领域有着广泛的应用。DES 的特点是易于制备、可生物降解、无毒、不易燃。当 DES 的一种或多种成分是活性药物成分(API)时,它们被命名为治疗用深层共晶溶剂(THEDES)。制备深共晶溶剂是为了提高原料药的溶解度和/或渗透性。本综述简要概述了迄今为止报道的具有抗菌和/或抗癌活性的最重要的 THEDES。此外,还讨论了制备 THEDES 所面临的挑战和局限性。本文介绍的工作表明了 THEDES 作为一种有前途的给药系统的重要性,它可以克服生物利用度问题,同时保留或增强其成分的生物活性。
{"title":"Applications of therapeutic deep eutectic solvents (THEDESs) as antimicrobial and anticancer agents.","authors":"Hala Bakr El-Nassan","doi":"10.1080/10837450.2024.2421786","DOIUrl":"10.1080/10837450.2024.2421786","url":null,"abstract":"<p><p>Deep eutectic solvents (DESs) are green alternatives to ionic liquids with wide applications in organic synthesis and catalysis. DESs are characterized by being easily prepared, biodegradable, nontoxic, and noninflammable. When one or more of the DES components is active pharmaceutical ingredient (API), the eutectic mixtures are named as therapeutic deep eutectic solvents (THEDESs). THEDESs are prepared in order to improve the solubility and/or the permeability of the APIs. This review presents a brief summary of the most important THEDESs reported to date having antimicrobial and/or anticancer activities. The challenges and limitations of THEDES preparation were also discussed. The work presented here indicated the importance of THEDES as a promising drug delivery system that can overcome the bioavailability problems while retaining or enhancing the biological activity of its components.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1084-1092"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Mechanistic characterization of fast dissolving PVP-I powder with multipolymer approaches and investigation on their molecular interaction. 采用多聚物方法快速溶解 PVP-I 粉末的机理特征及其分子相互作用研究。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-01 Epub Date: 2024-11-21 DOI: 10.1080/10837450.2024.2428772
Maytawee Wutthichokmongkhonkul, Rutthapol Sritharadol, Teerapol Srichana

Povidone-iodine (PVP-I) is widely used as an antiseptic in medical applications. However, its effectiveness is limited by certain drawbacks, such as low solubility in water and high volatility. Therefore, a formulation of a stable solid PVP-I is desirable. In this study, complexes of molecular PVP-I with polyethylene glycol-polyvinyl alcohol copolymer (PEG-PVA copolymer) were considered water-soluble iodophors. Two different methods were used to prepare the solids: physical mixtures and kneading. The physical characteristics of the obtained solids were evaluated using several spectroscopic methods. The presence of iodine was confirmed by a potentiometric titration and antimicrobial activity was tested. The results showed that the PEG-PVA copolymer interacted with povidone primarily through hydrogen bonding between the hydroxyl part of the PEG-PVA copolymer and the amide part of povidone with an estimated binding energy of 3.2 kcal/mol. The amide groups polarity in povidone made them more likely to form hydrogen bonds with the PEG-PVA copolymer. Also, the protonated pyrrolidone bonded to the triiodide anions by intermolecular hydrogen bonds, which increased PVP-I solubility in water. The kneading method provided a faster dissolution rate than physical mixing and pure PVP-I. The iodine contents were within an acceptable range (10-12%), and the antimicrobial activity proved effective against Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus mutans.

聚维酮碘(PVP-I)被广泛用作医疗应用中的消毒剂。然而,它的功效受到某些缺点的限制,如在水中的溶解度低和挥发性强。因此,我们需要一种稳定的固体 PVP-I 配方。在本研究中,PVP-I 分子与聚乙二醇-聚乙烯醇共聚物(PEG-PVA 共聚物)的复合物被认为是水溶性碘剂。制备固体的方法有两种:物理混合物和捏合。使用几种光谱方法对所得固体的物理特性进行了评估。通过电位滴定法确认了碘的存在,并测试了抗菌活性。结果表明,PEG-PVA 共聚物与聚维酮的相互作用主要是通过 PEG-PVA 共聚物的羟基部分与聚维酮的酰胺部分之间的氢键,估计结合能为 3.2 kcal/mol。聚维酮中的酰胺基团极性使其更有可能与 PEG-PVA 共聚物形成氢键。此外,质子化的吡咯烷酮通过分子间氢键与三碘化阴离子结合,从而增加了 PVP-I 在水中的溶解度。与物理混合法和纯 PVP-I 相比,捏合法的溶解速度更快。碘含量在可接受的范围内(10-12%),抗菌活性对金黄色葡萄球菌、表皮葡萄球菌和变异链球菌有效。
{"title":"Mechanistic characterization of fast dissolving PVP-I powder with multipolymer approaches and investigation on their molecular interaction.","authors":"Maytawee Wutthichokmongkhonkul, Rutthapol Sritharadol, Teerapol Srichana","doi":"10.1080/10837450.2024.2428772","DOIUrl":"10.1080/10837450.2024.2428772","url":null,"abstract":"<p><p>Povidone-iodine (PVP-I) is widely used as an antiseptic in medical applications. However, its effectiveness is limited by certain drawbacks, such as low solubility in water and high volatility. Therefore, a formulation of a stable solid PVP-I is desirable. In this study, complexes of molecular PVP-I with polyethylene glycol-polyvinyl alcohol copolymer (PEG-PVA copolymer) were considered water-soluble iodophors. Two different methods were used to prepare the solids: physical mixtures and kneading. The physical characteristics of the obtained solids were evaluated using several spectroscopic methods. The presence of iodine was confirmed by a potentiometric titration and antimicrobial activity was tested. The results showed that the PEG-PVA copolymer interacted with povidone primarily through hydrogen bonding between the hydroxyl part of the PEG-PVA copolymer and the amide part of povidone with an estimated binding energy of 3.2 kcal/mol. The amide groups polarity in povidone made them more likely to form hydrogen bonds with the PEG-PVA copolymer. Also, the protonated pyrrolidone bonded to the triiodide anions by intermolecular hydrogen bonds, which increased PVP-I solubility in water. The kneading method provided a faster dissolution rate than physical mixing and pure PVP-I. The iodine contents were within an acceptable range (10-12%), and the antimicrobial activity proved effective against <i>Staphylococcus aureus</i>, <i>Staphylococcus epidermidis</i>, and <i>Streptococcus mutans</i>.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1162-1174"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Formulation and evaluation of ibrutinib-loaded glycyrrhizic acid conjugated ovalbumin nanoparticles and ibrutinib-glycyrrhizic acid complex for improved oral bioavailability.
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-01 Epub Date: 2024-12-06 DOI: 10.1080/10837450.2024.2436190
Prateeksha Prakash Kamath, Pragathi Devanand Bangera, Divya Dhatri Kara, Rajeshwari Roychowdhury, Vamshi Krishna Tippavajhala, Mahalaxmi Rathnanand

The study aimed at enhancing the oral bioavailability of the BCS class 2 drug Ibrutinib (IBR), which exhibits low solubility (0.002 mg/mL) and high permeability (3.9% oral bioavailability). This was achieved through the formulation and evaluation of Ibrutinib-loaded Glycyrrhizic acid conjugated egg ovalbumin nanoparticles (IBR-GA-EA NPs) and Ibrutinib-Glycyrrhizic acid complex (IBR-GA-COMP). The formulation of Ibrutinib-Glycyrrhizic acid complex aimed to enhance the oral bioavailability of Ibrutinib. Lyophilized Ibrutinib-Glycyrrhizic acid complex was prepared and characterized through various studies including DSC, FTIR, in vitro release, and in vivo pharmacokinetics studies. DSC and FTIR confirmed successful formulation development. The nanoparticles exhibited spherical morphology with favourable characteristics: particle size of 194.10 nm, PDI of 0.22, and zeta potential of -33.96 mV. Encapsulation efficiency was 82.88%. In vitro release study displayed major improvement in drug release pattern compared to the free drug suspension. In vivo pharmacokinetic studies demonstrated 3.21-fold and 3.41-fold increase in the oral bioavailability of IBR-GA-EA NPs and IBR-GA-COMP, respectively, compared to IBR suspension alone. The formulated IBR-GA-EA NPs and IBR-GA-COMP are promising drug delivery methods as they successfully improve the solubility and oral bioavailability of Ibrutinib.

{"title":"Formulation and evaluation of ibrutinib-loaded glycyrrhizic acid conjugated ovalbumin nanoparticles and ibrutinib-glycyrrhizic acid complex for improved oral bioavailability.","authors":"Prateeksha Prakash Kamath, Pragathi Devanand Bangera, Divya Dhatri Kara, Rajeshwari Roychowdhury, Vamshi Krishna Tippavajhala, Mahalaxmi Rathnanand","doi":"10.1080/10837450.2024.2436190","DOIUrl":"10.1080/10837450.2024.2436190","url":null,"abstract":"<p><p>The study aimed at enhancing the oral bioavailability of the BCS class 2 drug Ibrutinib (IBR), which exhibits low solubility (0.002 mg/mL) and high permeability (3.9% oral bioavailability). This was achieved through the formulation and evaluation of Ibrutinib-loaded Glycyrrhizic acid conjugated egg ovalbumin nanoparticles (IBR-GA-EA NPs) and Ibrutinib-Glycyrrhizic acid complex (IBR-GA-COMP). The formulation of Ibrutinib-Glycyrrhizic acid complex aimed to enhance the oral bioavailability of Ibrutinib. Lyophilized Ibrutinib-Glycyrrhizic acid complex was prepared and characterized through various studies including DSC, FTIR, <i>in vitro</i> release, and <i>in vivo</i> pharmacokinetics studies. DSC and FTIR confirmed successful formulation development. The nanoparticles exhibited spherical morphology with favourable characteristics: particle size of 194.10 nm, PDI of 0.22, and zeta potential of -33.96 mV. Encapsulation efficiency was 82.88%. <i>In vitro</i> release study displayed major improvement in drug release pattern compared to the free drug suspension. <i>In vivo</i> pharmacokinetic studies demonstrated 3.21-fold and 3.41-fold increase in the oral bioavailability of IBR-GA-EA NPs and IBR-GA-COMP, respectively, compared to IBR suspension alone. The formulated IBR-GA-EA NPs and IBR-GA-COMP are promising drug delivery methods as they successfully improve the solubility and oral bioavailability of Ibrutinib.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1185-1198"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142789634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
In vitro skin permeation of flavonoid esters enzymatically derived from natural oils: release mechanism from gel emulsion, stability, and dermatological compatibility. 从天然油中酶解提取的类黄酮酯的体外皮肤渗透性:凝胶乳液的释放机制、稳定性和皮肤相容性。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-01 Epub Date: 2024-11-09 DOI: 10.1080/10837450.2024.2424977
Ana Milivojević, Marija Ćorović, Anja Petrov Ivanković, Milica Simović, Katarina Banjanac, Rada Pjanović, Dejan Bezbradica

Due to their broad spectrum of biological activities and attractive pharmacological properties, flavonoids are very promising molecules for application in skin care products. In this study, phloridzin and naringin medium- and long-chain fatty acid esters were enzymatically synthesized in reaction with natural oils (coconut and linseed oil) and in vitro transdermal delivery of synthesized esters through artificial Strat-M® membrane was investigated. Experimental results were succesfully fitted using Peppas and Sahlin model which includes the lag phase. Release kinetics of all examined flavonoid esters from gel emulsions through the membrane depended on both diffusion and polymer relaxation effect (0.5<n < 1). The estimated effective diffusion coefficients ranged from 0.168·10-8 to 6.149·10-8 cm2 s-1 for phloridzin esters and from 0.116·10-8 to 4.210·10-8 cm2 s-1 for naringin esters. The effective diffusion coefficients decreased with the increase in ester molecular weight indicating the size-dependent diffusion. All formulation showed good stability, excellent hydration effect, and excellent dermatological compatibility without irritating effect. It can be concluded that gel emulsions with a mixture of flavonoid esters enzymatically synthesized in reaction with vegetable oils can be effectively topically applied as a skin care products.

由于黄酮类化合物具有广谱的生物活性和诱人的药理特性,因此是非常有希望应用于护肤品的分子。本研究用天然油脂(椰子油和亚麻籽油)与酶反应合成了氯啶和柚皮苷中长链脂肪酸酯,并研究了合成酯通过人工 Strat-M® 膜进行体外透皮给药的情况。实验结果成功地与 Peppas 和 Sahlin 模型相吻合,其中包括滞后期。所有受试黄酮类酯类从凝胶乳液中通过膜的释放动力学都取决于扩散和聚合物松弛效应(氯嗪酯类为 0.5 -8 至 6.149-10-8 cm2 s-1,柚皮苷酯类为 0.116-10-8 至 4.210-10-8 cm2 s-1)。有效扩散系数随着酯分子量的增加而降低,这表明扩散与分子量有关。所有配方都表现出良好的稳定性、出色的保湿效果和出色的皮肤相容性,且无刺激作用。由此可以得出结论,含有与植物油反应酶解合成的黄酮类酯混合物的凝胶乳液可作为护肤产品有效地局部使用。
{"title":"<i>In vitro</i> skin permeation of flavonoid esters enzymatically derived from natural oils: release mechanism from gel emulsion, stability, and dermatological compatibility.","authors":"Ana Milivojević, Marija Ćorović, Anja Petrov Ivanković, Milica Simović, Katarina Banjanac, Rada Pjanović, Dejan Bezbradica","doi":"10.1080/10837450.2024.2424977","DOIUrl":"10.1080/10837450.2024.2424977","url":null,"abstract":"<p><p>Due to their broad spectrum of biological activities and attractive pharmacological properties, flavonoids are very promising molecules for application in skin care products. In this study, phloridzin and naringin medium- and long-chain fatty acid esters were enzymatically synthesized in reaction with natural oils (coconut and linseed oil) and <i>in vitro</i> transdermal delivery of synthesized esters through artificial Strat-M<sup>®</sup> membrane was investigated. Experimental results were succesfully fitted using Peppas and Sahlin model which includes the <i>lag</i> phase. Release kinetics of all examined flavonoid esters from gel emulsions through the membrane depended on both diffusion and polymer relaxation effect (0.5<<i>n</i> < 1). The estimated effective diffusion coefficients ranged from 0.168·10<sup>-8</sup> to 6.149·10<sup>-8</sup> cm<sup>2</sup> s<sup>-1</sup> for phloridzin esters and from 0.116·10<sup>-8</sup> to 4.210·10<sup>-8</sup> cm<sup>2</sup> s<sup>-1</sup> for naringin esters. The effective diffusion coefficients decreased with the increase in ester molecular weight indicating the size-dependent diffusion. All formulation showed good stability, excellent hydration effect, and excellent dermatological compatibility without irritating effect. It can be concluded that gel emulsions with a mixture of flavonoid esters enzymatically synthesized in reaction with vegetable oils can be effectively topically applied as a skin care products.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1121-1132"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Correction. 更正。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-01 Epub Date: 2024-11-18 DOI: 10.1080/10837450.2024.2428508
{"title":"Correction.","authors":"","doi":"10.1080/10837450.2024.2428508","DOIUrl":"10.1080/10837450.2024.2428508","url":null,"abstract":"","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1199-1200"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Ionic liquids and their potential use in development and improvement of drug delivery systems: evidence of their tendency to promote drug accumulation in the brain. 离子液体及其在开发和改进给药系统中的潜在用途:有证据表明离子液体有促进药物在大脑中蓄积的倾向。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-01 Epub Date: 2024-10-18 DOI: 10.1080/10837450.2024.2417004
William Eades, Shayan Abdolmohammadpourbonab, Linh Dinh, Bingfang Yan

Ionic liquids (ILs) are considered salt in liquid state, which is composed of organic cations and anions with low melting points (<100 °C). ILs have become a major scientific area with an extensive range of applications including chemistry, electrochemistry, and pharmaceutics. ILs have received great research interest in the pharmaceutical field as solvents, anti-solvents, co-solvents, and reagents in synthesis and formulation. While therapeutic ILs have been investigated for oral and trans-dermal drug delivery systems showing promising compatibility with a wide range of therapeutics, enhanced drug permeation through the skin, and cell membrane solvation to open channels to facilitate molecular passage, their potential to cross the challenging blood-brain barrier (BBB) remains an unanswered question. IL-based therapies could potentially be a game changer for improving drug delivery to cellular targets both at and across the BBB. In this review, we discuss (1) the tunable physicochemical properties of ILs; (2) the vast and various applications of ILs in the development and improvement of drug delivery systems; and (3) ILs as a potential approach for increasing drug accumulation in the brain tissue.

离子液体(IL)被认为是液态盐,它由熔点较低的有机阳离子和阴离子组成(如图 1 所示)。
{"title":"Ionic liquids and their potential use in development and improvement of drug delivery systems: evidence of their tendency to promote drug accumulation in the brain.","authors":"William Eades, Shayan Abdolmohammadpourbonab, Linh Dinh, Bingfang Yan","doi":"10.1080/10837450.2024.2417004","DOIUrl":"10.1080/10837450.2024.2417004","url":null,"abstract":"<p><p>Ionic liquids (ILs) are considered salt in liquid state, which is composed of organic cations and anions with low melting points (<100 °C). ILs have become a major scientific area with an extensive range of applications including chemistry, electrochemistry, and pharmaceutics. ILs have received great research interest in the pharmaceutical field as solvents, anti-solvents, co-solvents, and reagents in synthesis and formulation. While therapeutic ILs have been investigated for oral and trans-dermal drug delivery systems showing promising compatibility with a wide range of therapeutics, enhanced drug permeation through the skin, and cell membrane solvation to open channels to facilitate molecular passage, their potential to cross the challenging blood-brain barrier (BBB) remains an unanswered question. IL-based therapies could potentially be a game changer for improving drug delivery to cellular targets both at and across the BBB. In this review, we discuss (1) the tunable physicochemical properties of ILs; (2) the vast and various applications of ILs in the development and improvement of drug delivery systems; and (3) ILs as a potential approach for increasing drug accumulation in the brain tissue.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1065-1074"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Meloxicam-amino acids salts/ion pair complexes with advanced solubility, dissolution, and gastric safety. 美洛昔康-氨基酸盐/离子对复合物,具有更高的溶解度、溶解性和胃安全性。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-01 Epub Date: 2024-10-24 DOI: 10.1080/10837450.2024.2417766
Hamdy Abdelkader, Adel Al Fatease, Zeinab Fathalla, Mai E Shoman, Heba A Abou-Taleb

Amino acids have attracted attention as a potential functional excipient for optimizing biopharmaceutics characteristics of poorly soluble drugs. The amino acids are a diverse class with many functional groups, natural compounds, biocompatible, and low-molecular-weight substances. Two amino acids serine and arginine were investigated with meloxicam. Meloxicam has extremely low solubility; being NSAIDs, gastric upset, and ulcer are common side effects. Solid dispersions were produced by precipitation and physical mixing techniques. The produced combinations underwent in vitro dissolution, docking, DSC, FTIR, XRD, solubility, and gastric ulcer formation studies. Docking indicated ion pair/salt formation between the basic amino acid arginine and meloxicam. Both solubility and dissolution rates were increased by up to 3000-fold and 12-fold, respectively. DSC, FTIR an XRD supported these findings. Rats treated with meloxicam showed loss of surface gastric epithelium integrity and ulceration. The animal group received meloxicam: arginine showed intact gastric mucosa with the surface epithelium and gastric glands well organized and nearly similar to the untreated control. Arginine with the guanidine group that was capable of preserving gastric mucosa after repeated administration for 10 days. This study highlighted the role of arginine as a functional excipient that did not only improve solubility and dissolution rates but ameliorated the long-standing gastric side effects attributed to meloxicam.

氨基酸作为一种潜在的功能性辅料,在优化难溶性药物的生物制药特性方面备受关注。氨基酸种类繁多,具有多种功能基团、天然化合物、生物相容性和低分子量物质。我们对丝氨酸和精氨酸这两种氨基酸与美洛昔康进行了研究。美洛昔康的溶解度极低;作为非甾体抗炎药,胃部不适和溃疡是常见的副作用。通过沉淀和物理混合技术制备了固体分散体。对制备的组合物进行了体外溶解、对接、DSC、傅立叶变换红外光谱、XRD、溶解度和胃溃疡形成研究。对接表明,碱性氨基酸精氨酸与美洛昔康之间形成了离子对/盐。溶解度和溶解速率分别提高了 3000 倍和 12 倍。DSC、傅立叶变换红外光谱和 X 射线衍射证实了这些发现。接受美洛昔康治疗的大鼠表面胃上皮细胞完整性丧失,并出现溃疡。接受美洛昔康:精氨酸治疗的动物组显示出完整的胃黏膜,表面上皮和胃腺组织良好,与未治疗的对照组几乎相似。精氨酸与胍基组在重复给药 10 天后能够保留胃黏膜。这项研究强调了精氨酸作为功能性辅料的作用,它不仅提高了溶解度和溶解速率,还改善了美洛昔康长期存在的胃部副作用。
{"title":"Meloxicam-amino acids salts/ion pair complexes with advanced solubility, dissolution, and gastric safety.","authors":"Hamdy Abdelkader, Adel Al Fatease, Zeinab Fathalla, Mai E Shoman, Heba A Abou-Taleb","doi":"10.1080/10837450.2024.2417766","DOIUrl":"10.1080/10837450.2024.2417766","url":null,"abstract":"<p><p>Amino acids have attracted attention as a potential functional excipient for optimizing biopharmaceutics characteristics of poorly soluble drugs. The amino acids are a diverse class with many functional groups, natural compounds, biocompatible, and low-molecular-weight substances. Two amino acids serine and arginine were investigated with meloxicam. Meloxicam has extremely low solubility; being NSAIDs, gastric upset, and ulcer are common side effects. Solid dispersions were produced by precipitation and physical mixing techniques. The produced combinations underwent <i>in vitro</i> dissolution, docking, DSC, FTIR, XRD, solubility, and gastric ulcer formation studies. Docking indicated ion pair/salt formation between the basic amino acid arginine and meloxicam. Both solubility and dissolution rates were increased by up to 3000-fold and 12-fold, respectively. DSC, FTIR an XRD supported these findings. Rats treated with meloxicam showed loss of surface gastric epithelium integrity and ulceration. The animal group received meloxicam: arginine showed intact gastric mucosa with the surface epithelium and gastric glands well organized and nearly similar to the untreated control. Arginine with the guanidine group that was capable of preserving gastric mucosa after repeated administration for 10 days. This study highlighted the role of arginine as a functional excipient that did not only improve solubility and dissolution rates but ameliorated the long-standing gastric side effects attributed to meloxicam.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1075-1083"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
In vitro cellular uptake and insulin secretion studies on INS-1E cells of exendin-4-loaded self-nanoemulsifying drug delivery systems. 装载 Exendin-4 的自纳米乳化给药系统对 INS-1E 细胞的体外细胞吸收和胰岛素分泌研究。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-01 Epub Date: 2024-11-08 DOI: 10.1080/10837450.2024.2423823
Merve Çelik Tekeli, Yaprak Yalçın, Hasibe Verdi, Yeşim Aktaş, Nevin Çelebi

Exendin-4 (ex-4) is a peptide molecule that regulates blood glucose levels without causing hypoglycemia by providing insulin secretion from beta cells in the pancreas. Self-nanoemulsifying drug delivery systems (SNEDDS) attract attention for oral administration of therapeutic peptide/proteins because they protect therapeutic peptide/proteins from the gastric environment, reduce changes due to food effects, are easy to prepare and scale-up. Ex-4 has no commercial form that can be administered orally. In this study, the cytotoxicity, cellular uptake, and insulin secretion of ex-4 and ex-4/chymostatin (chym) SNEDDS were investigated on INS-1E rat pancreatic beta cells. The effect of ex-4 and ex-4/chym SNEDDS on cell viability in INS-1E cells increased when the dilution ratio higher. Ex-4 and ex-4/chym SNEDDS increased insulin levels in 2.8 mM (low-dose) glucose-induced INS-1E cells 2.21-fold and 2.17-fold compared to control, respectively. Ex-4 and ex-4/chym SNEDDS increased insulin levels in 16.7 mM (high dose) glucose-induced INS-1E cells compared to control, respectively. In cellular uptake studies, coumarin-6 solution penetrated the apical membrane of INS-1E cells and remained in the cytoplasm, while coumarin-6 loaded SNEDDS were visualized in the nuclei of the cell. These findings will likely be useful in the development of new formulations for the oral administration of peptides/proteins.

Exendin-4(ex-4)是一种多肽分子,可通过胰腺β细胞分泌胰岛素来调节血糖水平,而不会导致低血糖。自纳米乳化给药系统(SNEDDS)在治疗肽/蛋白质的口服给药方面备受关注,因为它能保护治疗肽/蛋白质不受胃环境影响,减少食物影响引起的变化,易于制备和放大。Ex-4 还没有可以口服的商业形式。本研究研究了 ex-4 和 ex-4/chymostatin (chym) SNEDDS 对 INS-1E 大鼠胰腺 beta 细胞的细胞毒性、细胞摄取和胰岛素分泌。当稀释率越高时,ex-4 和 ex-4/chym SNEDDS 对 INS-1E 细胞活力的影响越大。与对照组相比,ex-4 和 ex-4/chym SNEDDS 使 2.8 mM(低剂量)葡萄糖诱导的 INS-1E 细胞中的胰岛素水平分别提高了 2.21 倍和 2.17 倍。与对照组相比,ex-4 和 ex-4/chym SNEDDS 可分别提高 16.7 毫摩尔(高剂量)葡萄糖诱导的 INS-1E 细胞中的胰岛素水平。在细胞摄取研究中,香豆素-6溶液穿透了INS-1E细胞的顶端膜,并停留在细胞质中,而在细胞核中可以看到香豆素-6负载的SNEDDS。这些发现可能有助于开发口服多肽/蛋白质的新制剂。
{"title":"<i>In vitro</i> cellular uptake and insulin secretion studies on INS-1E cells of exendin-4-loaded self-nanoemulsifying drug delivery systems.","authors":"Merve Çelik Tekeli, Yaprak Yalçın, Hasibe Verdi, Yeşim Aktaş, Nevin Çelebi","doi":"10.1080/10837450.2024.2423823","DOIUrl":"10.1080/10837450.2024.2423823","url":null,"abstract":"<p><p>Exendin-4 (ex-4) is a peptide molecule that regulates blood glucose levels without causing hypoglycemia by providing insulin secretion from beta cells in the pancreas. Self-nanoemulsifying drug delivery systems (SNEDDS) attract attention for oral administration of therapeutic peptide/proteins because they protect therapeutic peptide/proteins from the gastric environment, reduce changes due to food effects, are easy to prepare and scale-up. Ex-4 has no commercial form that can be administered orally. In this study, the cytotoxicity, cellular uptake, and insulin secretion of ex-4 and ex-4/chymostatin (chym) SNEDDS were investigated on INS-1E rat pancreatic beta cells. The effect of ex-4 and ex-4/chym SNEDDS on cell viability in INS-1E cells increased when the dilution ratio higher. Ex-4 and ex-4/chym SNEDDS increased insulin levels in 2.8 mM (low-dose) glucose-induced INS-1E cells 2.21-fold and 2.17-fold compared to control, respectively. Ex-4 and ex-4/chym SNEDDS increased insulin levels in 16.7 mM (high dose) glucose-induced INS-1E cells compared to control, respectively. In cellular uptake studies, coumarin-6 solution penetrated the apical membrane of INS-1E cells and remained in the cytoplasm, while coumarin-6 loaded SNEDDS were visualized in the nuclei of the cell. These findings will likely be useful in the development of new formulations for the oral administration of peptides/proteins.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1101-1110"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
期刊
Pharmaceutical Development and Technology
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1