AAPS PharmSciTech最新文献_第7页

Exploring co-milling of poorly water-soluble drugs with swellable polymers to enhance the dissolution rate 探索水溶性差的药物与可膨胀聚合物的共磨，以提高溶解速度

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2025-11-14 DOI: 10.1208/s12249-025-03270-w

Nicolas Pätzmann, Josef Beránek, Brendan T. Griffin, Martin Kuentz, Patrick J. O’Dwyer

Co-milling with excipients offers an effective solvent-free strategy to enhance the dissolution of drugs in the pharmaceutical industry. Nonetheless, the range of excipients available for co-milling, as well as the selection criteria, remains relatively unexplored. Therefore, this study aims to evaluate the effect of co-milling with crosslinked swellable polymers on the dissolution of poorly water-soluble drugs. A structurally diverse set of crystalline compounds (n = 13) were co-milled with the three commonly used tablet disintegrants: Croscarmellose sodium, sodium starch glycolate and crospovidone. In vitro dissolution profiles were assessed to evaluate the excipient performance and identify crucial drug descriptors relating to co-milling induced dissolution enhancement. All 39 co-milled formulations showed an increased drug intrinsic dissolution rate (IDR), with drug properties such as molecular size and polar surface area showing a positive correlation with the extent of IDR enhancement following co-milling. Moreover, co-milling consistently yielded greater initial dissolution (AUC_0-5 min) across all excipients compared to milling the drug without an excipient. On average, milling with croscarmellose sodium produced the greatest improvement in the early stages of dissolution for neutral and basic compounds, while sodium starch glycolate was more effective in enhancing the dissolution of co-milled acidic drugs. Furthermore, an assessment within the refined Developability Classification System (rDCS) revealed that co-milling was effective to overcome dissolution rate limitations for all rDCS class IIa drugs. This study establishes a practical framework for the broader application of co-milling with tablet disintegrants and demonstrates its relevance within the latest rDCS paradigm for overcoming dissolution rate-limited absorption.

Graphical Abstract

与赋形剂共磨提供了一种有效的无溶剂策略，以提高药物的溶解在制药工业。尽管如此，可用于共磨辅料的范围，以及选择标准，仍然相对未被探索。因此，本研究旨在评价与交联可膨胀聚合物共磨对难水溶性药物溶解的影响。采用三种常用的片剂崩解剂：交联棉糖钠、淀粉乙醇酸钠和交联维酮共磨得到结构多样的晶体化合物（n = 13）。评估体外溶出谱，以评估赋形剂的性能，并确定与共磨诱导溶出增强有关的关键药物描述符。所有39种共磨制剂均显示出药物固有溶出率（IDR）的提高，药物性质（如分子大小和极性表面积）与共磨后药物固有溶出率的提高程度呈正相关。此外，与不加辅料的药物研磨相比，所有辅料的共磨始终产生更大的初始溶出（AUC0-5分钟）。平均而言，用交联棉糖钠研磨对中性和碱性化合物的早期溶解有最大的改善，而淀粉乙醇酸钠对共研磨的酸性药物的溶解更有效。此外，在改进的可显像性分类系统（rDCS）中进行的评估表明，共磨可有效克服所有rDCS IIa类药物的溶出率限制。本研究为片剂共磨的更广泛应用建立了一个实践框架，并证明了其在克服溶出速率限制吸收的最新rDCS范例中的相关性。图形抽象

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引用次数: 0

A Self-healable Hydrogel for Co-delivery of Hot-Melt Extruded System With Curcumin and Hesperetin Intended for Topical Application 用于局部应用的姜黄素和橙皮素热熔挤出系统的自愈合水凝胶

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2025-11-14 DOI: 10.1208/s12249-025-03290-6

Joanna Szymczak, Kamil Wdowiak, Sylwia Różańska, Jacek Różański, Tomasz Plech, Judyta Cielecka-Piontek

Hot-melt extrusion is an effective method for enhancing the solubility of weakly water-soluble compounds through amorphization, but the obtained powder form does not provide sufficient skin adherence or residence time, thus requiring incorporation into a suitable carrier for topical delivery. Hydrogels can serve as an appropriate carriers for such systems, offering additional characteristics such as self-healing and pH-responsiveness. Therefore, our research aimed to develop a hydrogel carrier with distinct features for a hot-melt extruded system containing curcumin and hesperetin, both having anti-cancer activity against skin cancer. We used a double cross-linking method with tannic acid and aluminum ions to prepare three hydrogels with different ratio of these agents, characterized by ATR-FTIR and rheological tests. Swelling studies in buffers of varying pH and in vitro release tests in pH 5.5 showed significant pH-responsive swelling and varying release rates of active compounds, influenced by cross-linking degrees. The prepared hydrogels swelled significantly, with percentages ranging from 170 to 4016%, with the maximum swelling at pH 5.5. Hesperetin release was measured as 84.92 ± 0.03%, 84.21 ± 1.21%, and 80.75 ± 2.76% in formulations H0, H1, and H2, respectively. While the release rate of curcumin increased with the degree of cross-linking, reaching 9.03 ± 0.07%, 26.43 ± 1.16%, and 27.31 ± 2.51%, respectively. In addition, a qualitative analysis with optical microscope confirmed the produced hydrogel's self-healing characteristics. Our findings provide a novel approach to improve the co-delivery of amorphous curcumin and hesperetin compounds to the skin.

Graphical Abstract

热熔挤压是通过非晶化提高弱水溶性化合物溶解度的有效方法，但获得的粉末形式不能提供足够的皮肤粘附性或停留时间，因此需要掺入合适的载体中进行局部递送。水凝胶可以作为这种系统的合适载体，具有自我修复和ph响应性等附加特性。因此，我们的研究旨在开发一种具有独特特征的水凝胶载体，用于含有姜黄素和橙皮素的热熔挤出体系，这两种物质都具有抗癌皮肤癌的活性。采用单宁酸和铝离子双交联法制备了三种不同配比的水凝胶，并通过ATR-FTIR和流变学试验对其进行了表征。不同pH缓冲液的溶胀研究和pH 5.5的体外释放试验表明，受交联度的影响，活性化合物的pH响应性溶胀和不同的释放率。制备的水凝胶溶胀明显，溶胀率为170 ~ 4016%，pH为5.5时溶胀率最大。H0、H1、H2的橙皮素释放量分别为84.92±0.03%、84.21±1.21%、80.75±2.76%。而姜黄素的释放率随着交联程度的增加而增加，分别达到9.03±0.07%、26.43±1.16%和27.31±2.51%。此外，光学显微镜定性分析证实了制备的水凝胶具有自愈特性。我们的发现提供了一种新的方法来改善无定形姜黄素和橙皮素化合物到皮肤的共同递送。图形抽象

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引用次数: 0

Novel Capsaicin Nanogel for Arthritic Pain and Inflammation Management: Formulation, In Vitro, Ex-vivo and In Vivo Assessment 用于关节炎疼痛和炎症管理的新型辣椒素纳米凝胶：配方，体外，离体和体内评估。

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2025-11-13 DOI: 10.1208/s12249-025-03273-7

Varsha Kadian, Babu Lal Jangir, Pooja Dalal, Sunil Kumar, Anroop Nair, Sweta Dalal, Rekha Rao

The present work aimed to prepare and evaluate novel capsaicin (CAP) loaded nanosponges (NS) embedded Carbopol hydrogel (CAPNS-HG) with rosemary oil (RO) for arthritis management. CAP loaded NS were formulated using melt technique employing diphenylcarbonate and β-cyclodextrin. To facilitate their dermal application, CAPNS were integrated with Carbopol 934 hydrogel using RO as a permeation enhancer. Nanogel samples so formed were analyzed for physicochemical and rheological properties, followed by their in vitro, ex vivo, and in vivo evaluations. Based on the findings herein, CAPNS-HG was found to exhibit favorable rheological characteristics (610.56 cP), effective skin permeation (31.410 ± 1.145 µg/cm²), and delayed-release (61.91% in 24 h). Further, the hydrogel was observed to follow Korsmeyer-Peppas release kinetics with the Fickian diffusion mechanism. Outcomes of the in vitro irritation study demonstrated that CAPNS-HG significantly reduced skin irritation (four times; CAP-HG 12.159 ± 2.502 and CAPNS-HG 03.497 ± 0.096), which was also validated from in vivo evaluations. Further, a remarkable decrease in inflammation (20.869 ± 0.13%) was noted in FCA-induced arthritic animals. Improved hematological profile along with histological and X-ray data substantiated reduction in arthritic symptoms in CAPNS-HG treated animals. Hence, it can be concluded from the findings that CAPNS-HG is a safer and more promising delivery option for alleviating complete FCA-induced symptoms. The combination of CAPNS with hydrogel further augmented the therapeutic efficiency, resulting in a novel formulation for pain and inflammation management in this chronic disorder.

Graphical Abstract

Illustration for evaluation of novel capsaicin nanogel (CAPNS-HG) with rosemary oil (RO) for dermal application in management of inflammatory arthritis

本研究旨在制备和评价一种新型辣椒素纳米海绵（NS）和迷迭香油包埋卡波波水凝胶（CAPNS-HG）对关节炎的治疗作用。以碳酸二苯酯和β-环糊精为原料，采用熔融法制备了负载CAP的NS。为了促进其皮肤应用，将CAPNS与Carbopol 934水凝胶结合，并使用RO作为渗透增强剂。对形成的纳米凝胶样品进行物理化学和流变性能分析，然后对其进行体外、离体和体内评价。实验结果表明，CAPNS-HG具有良好的流变特性（610.56 cP），有效皮肤渗透（31.410±1.145µg/cm2）， 24 h缓释（61.91%）。此外，观察到水凝胶符合Korsmeyer-Peppas释放动力学和Fickian扩散机制。体外刺激研究结果表明，CAPNS-HG显著降低皮肤刺激（4次；CAP-HG 12.159±2.502和CAPNS-HG 03.497±0.096），体内评价也验证了这一点。此外，fca诱导的关节炎动物的炎症明显减少（20.869±0.13%）。改善的血液学特征以及组织学和x射线数据证实了CAPNS-HG治疗动物关节炎症状的减轻。因此，从研究结果可以得出结论，CAPNS-HG是一种更安全、更有希望缓解fca诱导的完全症状的分娩选择。CAPNS与水凝胶的结合进一步提高了治疗效率，为这种慢性疾病的疼痛和炎症管理提供了一种新的配方。

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引用次数: 0

Long-Chained Fatty Acid-Based Solid Dispersions of Voriconazole as an Effective Strategy For Achieving Sustained Release 基于长链脂肪酸的伏立康唑固体分散体是实现缓释的有效策略。

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2025-11-12 DOI: 10.1208/s12249-025-03258-6

Urvi Modasiya, Kiran Dudhat, Sunny Shah, Chetan Borkhataria, Trupesh Pethani, Viral Shah, Chandankumar Pashavan, Gaurav Sanghvi, Akhil Hadiya, Mori Dhaval

Voriconazole (VCZ), a second-generation triazole antifungal agent, possesses high oral bioavailability but is associated with substantial pharmacokinetic variability influenced by food intake and physiological conditions. This study aimed to develop sustained-release solid dispersions (SDs) of VCZ using long-chain fatty acids—stearic acid (SA), palmitic acid (PA), and myristic acid (MA)—to modulate drug dissolution and improve pharmacokinetic consistency. SDs were prepared using the melt-fusion method at drug-to-fatty acid ratios of 0.5:1 and 1:1 (w/w) and were systematically characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), hot-stage polarized microscopy (HSM), Fourier-transform infrared spectroscopy (FTIR), intrinsic dissolution rate (IDR), and in vitro diffusion studies. The 1:1 (w/w) SDs exhibited markedly slower and sustained drug release compared to pure VCZ and physical mixtures under both acidic (0.1 N HCl) and stepwise dissolution study. PXRD confirmed that VCZ retained its crystalline nature within the formed SD. DSC and HSM indicated complete solubilization of VCZ in the molten carrier without recrystallization. FTIR studies revealed hydrogen bonding between VCZ and the fatty acids. Among the tested formulations, SD (VCZ:MA) provided the most favorable combination of sustained release and enhanced permeability, as evidenced by in vitro diffusion studies. Furthermore, minimum inhibitory concentration (MIC) testing confirmed that all SD formulations maintained antifungal activity. Overall, the findings highlight long-chain fatty acid–based SDs as a promising strategy for achieving sustained VCZ release and reducing pharmacokinetic variability, warranting further in vivo evaluation.

Graphical Abstract

伏立康唑（Voriconazole， VCZ）是第二代三唑类抗真菌药物，具有较高的口服生物利用度，但受食物摄入和生理条件的影响，其药代动力学变化较大。本研究旨在利用长链脂肪酸-硬脂酸（SA）、棕榈酸（PA）和肉豆酱酸（MA）制备VCZ缓释固体分散体（SDs），以调节药物溶出度，提高药动学一致性。采用药物与脂肪酸比为0.5:1和1:1 （w/w）的熔融熔融法制备SDs，并通过差示扫描量热法（DSC）、粉末x射线衍射（PXRD）、热级极化显微镜（HSM）、傅里叶变换红外光谱（FTIR）、固有溶出率（IDR）和体外扩散研究对SDs进行了系统表征。在酸性（0.1 N HCl）和逐步溶出研究中，与纯VCZ和物理混合物相比，1:1 (w/w) SDs的药物释放速度明显减慢和持续。PXRD证实了VCZ在形成的SD内保持了其晶体性质。DSC和HSM表明，VCZ在熔融载体中完全溶解，无再结晶。FTIR研究显示VCZ和脂肪酸之间存在氢键。体外扩散研究表明，SD （VCZ:MA）具有较好的缓释和增强渗透性的效果。此外，最低抑制浓度（MIC）测试证实所有SD制剂保持抗真菌活性。总的来说，研究结果强调了基于长链脂肪酸的SDs是实现持续VCZ释放和减少药代动力学变异性的有希望的策略，需要进一步的体内评估。

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引用次数: 0

A Review on Emerging Technologies in Pharmaceutical Packaging: From Anti-Counterfeiting to Green Solutions 药品包装新兴技术综述：从防伪到绿色解决方案。

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2025-11-11 DOI: 10.1208/s12249-025-03230-4

Krishang Sikaria, Amatha Sreedevi, Nandini Srivastava, Virendra S. Ligade, Pradeep Muragundi, Sreedhar D

This review article discusses recent innovations and developments in pharmaceutical packaging and its emerging trends in five areas of priority: anti-counterfeiting, drug monitoring, drug quality preservation, sustainability, and patient compliance. The increasing problem of counterfeit medicine has raised the necessity of numerous security technologies to fight the issue. Physical–chemical identifiers, including inks, pigments, and molecular taggants, as well as overt and covert characteristics like holograms, colour-shifting inks, and digital watermarks, assist in verifying the authenticity of pharmaceutical products. New technologies such as carbon dots and microstructural markers in forensic inks add extra security against counterfeiting. Radio Frequency Identification technology assists in product condition tracking, minimizing medical errors, and enhancing patient safety across the supply chain. Colorimetric indicators, like time–temperature indicators and vaccine vial monitors, visually convey environmental conditions and preserve temperature-sensitive drugs' integrity. Drug quality and integrity is another area of importance discussed in the review. Novel packaging technologies, like dual-chamber delivery systems, multilayer constructions, and coatings, offer superior barrier properties and protection against degradation. The review also discusses increasing focus on eco-friendly packaging alternatives, including using renewable, biodegradable, and recycled materials to reduce the ecological footprint of drug packaging. Lastly, the article investigates the role of smart packaging technologies in patient compliance improvement through reminder systems, status indicators, and single-medicine storage units that assist patients in following the prescribed medication regime.

Graphical Abstract

这篇综述文章讨论了药品包装的最新创新和发展及其在五个优先领域的新趋势：防伪、药品监测、药品质量保存、可持续性和患者依从性。假药问题日益严重，因此需要多种安全技术来解决这一问题。物理化学标识符，包括油墨、颜料和分子标记剂，以及像全息图、变色油墨和数字水印这样的显性和隐性特征，有助于验证药品的真实性。新技术，如碳点和法医油墨中的微结构标记，增加了防伪的额外安全性。射频识别技术有助于产品状态跟踪，最大限度地减少医疗错误，并提高整个供应链的患者安全。比色指标，如时间-温度指标和疫苗瓶监测器，直观地传达环境条件并保持对温度敏感的药物的完整性。药品质量和完整性是审查中讨论的另一个重要领域。新的包装技术，如双室输送系统、多层结构和涂层，提供了卓越的阻隔性能和防止降解的保护。该综述还讨论了越来越关注环保包装替代品，包括使用可再生、可生物降解和可回收材料来减少药物包装的生态足迹。最后，本文探讨了智能包装技术在患者依从性改善中的作用，通过提醒系统、状态指示器和单一药物存储单元，帮助患者遵循规定的药物制度。

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引用次数: 0

Pharmaceutical Formulations and Analytical Methods of Donepezil 多奈哌齐的制剂及分析方法。

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2025-11-11 DOI: 10.1208/s12249-025-03288-0

Vu Dang Hoang, Hue Minh Thi Nguyen, Tuan Anh Nguyen, Sanjay Garg

Donepezil is a selective acetylcholinesterase inhibitor widely prescribed for the symptomatic treatment of Alzheimer’s disease. As therapeutic needs grow and delivery systems evolve, ensuring product quality, efficacy, safety and patient compliance becomes increasingly important. Meanwhile, pharmaceutical formulation innovations can improve clinical outcomes and usability, and analytical methods help ensure accurate assessment of drug behavior and quality control. This narrative review first provides a concise overview of donepezil’s physicochemical properties and synthesis, then focuses on two interrelated domains: (i) pharmaceutical formulations and (ii) analytical methodologies. The former highlights advancements in novel delivery systems—such as liposomes, nanoparticles, microneedles, nasal gels, and long-acting injectable depots—developed to enhance brain targeting, prolong drug release, and reduce systemic side effects. The latter reviews validated analytical methods for quantifying and characterizing donepezil in pharmaceutical and biological matrices, with emphasis on RP-HPLC, LC–MS/MS, chiral separations, and emerging electrochemical and spectroscopic techniques. These analytical strategies are essential for evaluating formulation performance, monitoring drug stability, and ensuring regulatory compliance. Collectively, this review underscores that progress in both formulation design and analytical science is vital to optimizing donepezil-based therapies for Alzheimer’s disease management.

Graphical Abstract

多奈哌齐是一种选择性乙酰胆碱酯酶抑制剂，广泛用于阿尔茨海默病的对症治疗。随着治疗需求的增长和递送系统的发展，确保产品质量、疗效、安全性和患者依从性变得越来越重要。同时，药物配方创新可以改善临床效果和可用性，分析方法有助于确保药物行为的准确评估和质量控制。这篇叙述性综述首先提供了多奈哌齐的物理化学性质和合成的简明概述，然后侧重于两个相互关联的领域：(i)药物配方和（ii）分析方法。前者强调了新型给药系统的进步，如脂质体、纳米颗粒、微针、鼻凝胶和长效注射储库，这些系统的发展增强了大脑靶向性，延长了药物释放时间，减少了全身副作用。后者综述了多奈哌齐在药物和生物基质中的定量和表征分析方法，重点是RP-HPLC， LC-MS/MS，手性分离以及新兴的电化学和光谱技术。这些分析策略对于评估制剂性能、监测药物稳定性和确保法规遵从性至关重要。总的来说，这篇综述强调了配方设计和分析科学的进展对于优化以多奈哌齐为基础的阿尔茨海默病治疗至关重要。

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引用次数: 0

Development of Paclitaxel Injection Concentrate for Nanodispersion 纳米分散紫杉醇注射液浓缩液的研制。

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2025-11-11 DOI: 10.1208/s12249-025-03269-3

Ajay J. Khopade, Malay D. Shah, Bhushan Borole

This work provides details of development of paclitaxel injection concentrate for nanodispersion (PICN) which includes excipient screening, optimization process, and stability studies of the PICN formulation. A systematic evaluation of various fatty acids, sterol analogues, polymers, and solvents led to the selection of a synergistic excipient system for PICN consisting of sodium cholesterol sulphate, caprylic acid and povidone K12 dissolved in polyethylene glycol 400 and ethanol. PICN reliably forms nanodispersion with particle sizes in the 50–150 nm range upon reconstitution in 5% dextrose solution (D5W). Transmission electron microscopy of nanodispersion demonstrated that the nanoparticles are amorphous and non-crystalline which was confirmed by differential scanning calorimetry and X-ray diffraction studies showing a complete loss of paclitaxel crystallinity. Small angle X-ray scattering data showed that the nanoparticles exist in sponge-like coacervate phase. Reconstitution studies in D5W infusion bag, mimicking injection time and shaking speed of the diluent bag, showed minimal impact on particle size of the nanodispersion. The in-vitro release profile was consistent from the range of particle sizes produced. Stability data of PICN under ICH conditions confirmed assay values of 97–101% with low total impurities (< 0.65%) over 24 months. The stability of the reconstituted nanodispersion did not show any change in physicochemical quality attributes over 24 h. These results not only validate our hypothesis of paclitaxel self-assembly driven in the presence of selected lipid and polymers reported in previous paper but also demonstrates that a convenient, scalable and stable protein-free alternative to existing paclitaxel formulations is offered for clinical use.

Graphical Abstract

本文详细介绍了紫杉醇纳米分散体注射浓缩液（PICN）的研制，包括赋形剂的筛选、工艺的优化和PICN配方的稳定性研究。通过对各种脂肪酸、甾醇类似物、聚合物和溶剂的系统评估，选择了一种由硫酸胆固醇钠、辛酸和聚维酮K12溶解在聚乙二醇400和乙醇中的协同赋形剂系统。在5%葡萄糖溶液（D5W）中重构后，PICN可靠地形成粒径在50-150 nm范围内的纳米分散体。纳米分散体的透射电子显微镜显示纳米颗粒是无定形和非结晶的，差示扫描量热法和x射线衍射研究证实了这一点，表明紫杉醇结晶度完全丧失。小角度x射线散射数据表明，纳米颗粒呈海绵状凝聚相存在。在D5W注射袋中模拟注射时间和稀释剂袋的摇动速度进行重构研究，结果表明对纳米分散体粒径的影响最小。体外释放谱与所产生的颗粒大小范围一致。PICN在ICH条件下的稳定性数据证实，总杂质较低，测定值为97-101% (

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引用次数: 0

Biopolymeric Composite Films of Hyaluronic Acid and Gellan Gum for Localized and Sustained Azithromycin Delivery in Periodontal Therapy 透明质酸和结冷胶生物聚合物复合膜用于牙周治疗中阿奇霉素的局部和持续递送。

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2025-11-11 DOI: 10.1208/s12249-025-03265-7

Kunchorn Kerdmanee, Nuntachai Hanpramukkun, Ratana Charoenwattanasatien, Phakkhananan Pakawanit, Sucharat Limsitthichaikoon

This study reports the development of azithromycin-loaded polymeric films (AZF) composed of gellan gum (GG) and hyaluronic acid (HA) for localized periodontal drug delivery. A 3² full factorial design was employed to optimize formulation variables and assess critical attributes influencing film performance. The films exhibited uniform thickness (0.13–0.16 mm), high folding endurance (> 300 folds), and a physiologically compatible surface pH (6.8–7.0). Increasing HA content significantly enhanced swelling and drug release, with all formulations having achieved high drug-loading efficiencies (92-100%). In vitro drug release studies revealed a biphasic release profile, an initial burst for rapid antimicrobial action followed by sustained release over 72 hours. Kinetics modeling using the Peppas–Sahlin equation indicated contributions from both Fickian diffusion and polymer relaxation. AFM, SEM and XTM confirmed the films’ porous, uniform microstructure supporting sustained release behavior. AZF exhibited significantly superior antibacterial efficacy against Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, compared to standard azithromycin and metronidazole discs. The localized, sustained drug delivery effectively overcomes limitations of systemic antibiotic therapy, including poor site retention and the need for systemic exposure. These findings support the potential of GG–HA films as biodegradable, patient-compliant platforms for targeted periodontal drug delivery, offering improved therapeutic outcomes and addressing biological barriers to effective treatment.

Graphical Abstract

本研究报道了由结冷胶（GG）和透明质酸（HA）组成的阿奇霉素负载聚合物膜（AZF）的发展，用于局部牙周药物递送。采用32全因子设计优化配方变量，评估影响膜性能的关键属性。薄膜具有均匀的厚度（0.13-0.16 mm），高折叠耐力（> 300次）和生理相容的表面pH（6.8-7.0）。增加透明质酸含量可显著增强溶胀和药物释放，所有制剂均具有较高的载药效率（92-100%）。体外药物释放研究揭示了双相释放特征，最初的快速抗菌作用爆发，随后持续释放超过72小时。利用Peppas-Sahlin方程建立的动力学模型显示了菲克扩散和聚合物弛豫的共同作用。AFM、SEM和XTM证实了膜的多孔、均匀的微观结构支持缓释行为。与标准阿奇霉素和甲硝唑碟片相比，AZF对放线菌聚集菌和牙龈卟啉单胞菌的抑菌效果明显优于标准阿奇霉素碟片。局部、持续的给药有效地克服了全身抗生素治疗的局限性，包括不良的部位保留和需要全身暴露。这些发现支持了GG-HA膜作为靶向牙周药物输送的可生物降解、患者依从性平台的潜力，提供了更好的治疗效果，并解决了有效治疗的生物障碍。

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引用次数: 0

Utilizing Hot-Melt Extrusion and Spray Drying Techniques for Preparation of Liquid and Solid Cannabidiol Nano-Structured Lipid Carriers Formulations 利用热熔挤压和喷雾干燥技术制备液体和固体大麻二酚纳米结构脂质载体配方。

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2025-11-11 DOI: 10.1208/s12249-025-03277-3

Iman E. Taha, Mahmoud A. ElSohly, Nourhan Mostafa, Mashan Almutairi, Eman A. Ashour

Nanostructured lipid carriers (NLCs) have attracted considerable interest as drug delivery systems capable of enhancing the solubility and oral bioavailability of poorly water-soluble drugs. In our previous work, cannabidiol (CBD)-loaded NLCs prepared by hot homogenization demonstrated improved dissolution and oral bioavailability. In the present study, hot-melt extrusion (HME) was investigated as a rapid and easily scalable alternative method for the preparation of CBD NLCs. Additionally, spray drying was used to convert the prepared CBD NLCs into a solid dosage form. CBD NLCs were prepared using HME at different screw speeds (100, 200, and 300 rpm), followed by probe sonication, and characterized for particle size, entrapment efficiency (EE), and drug release. Spray drying was performed with different carriers (D-lactose, Kollidon® VA 64, maltodextrin 12, and Soluplus®) to evaluate their compatibility and performance. The results showed that the screw speed has an impact on the properties of the NLCs, while probe sonication further reduced particle size, resulting in enhanced entrapment efficiency, and drug release of all formulations. Although NLC produced at a screw speed of 300 rpm was the most stable in both 4 °C and 25 °C. Among the carriers tested for spray drying, maltodextrin achieved nearly complete CBD release, while Soluplus® led to increased particle size and reduced release. Overall, HME combined with probe sonication proved to be a robust approach for the preparation of CBD NLCs, which were successfully converted into solid powder formulations by spray drying, offering a promising strategy for scalable production of CBD NLCs.

Graphical Abstract

纳米结构脂质载体（nlc）作为一种能够提高水溶性差药物的溶解度和口服生物利用度的药物传递系统，已经引起了人们相当大的兴趣。在我们之前的工作中，通过热均质制备的负载大麻二酚（CBD）的NLCs显示出更好的溶解性和口服生物利用度。在本研究中，研究了热熔挤压（HME）作为一种快速且易于扩展的制备CBD NLCs的替代方法。此外，喷雾干燥将制备的CBD NLCs转化为固体剂型。以不同转速（100、200和300 rpm）的HME制备CBD NLCs，并进行探针超声，对其粒径、包埋效率（EE）和药物释放进行表征。用不同的载体（d -乳糖、Kollidon®VA 64、麦芽糊精12和Soluplus®）进行喷雾干燥，以评估它们的相容性和性能。结果表明，螺杆转速对纳米纤维素的性能有影响，而探针超声进一步减小了纳米纤维素的粒径，从而提高了纳米纤维素的包封效率和药物释放度。虽然在300 rpm转速下产生的NLC在4°C和25°C下都是最稳定的。在喷雾干燥测试的载体中，麦芽糊精几乎完全释放了CBD，而Soluplus®则增加了颗粒大小，减少了释放。总的来说，HME结合探针超声被证明是一种制备CBD NLCs的有效方法，通过喷雾干燥成功地将其转化为固体粉末配方，为CBD NLCs的规模化生产提供了一种有前途的策略。

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引用次数: 0

Overcoming Bioavailability Barriers: Optimized Hybrid Nanocarrier System to Amplify Berberine Absorption via Peyer’s Patches 克服生物利用度障碍：优化混合纳米载体系统放大小檗碱吸收通过Peyer's补丁。

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2025-11-11 DOI: 10.1208/s12249-025-03260-y

Shubhangi A. Thool, Varsha B. Pokharkar

Berberine, an isoquinoline alkaloid, is a compound of interest due to its structural diversity and wide range of biological activities; however, its pharmacological effects are significantly limited by poor intestinal absorption. In this study, a novel formulation approach was employed to improve the bioavailability of berberine by formulating lipid-polymer hybrid nanoparticles (BER-LPHN) using a modified nanoprecipitation method. The formulation was optimized using a 3² full factorial design, incorporating Phospholipon 90 H as the lipid and Gantrez as the hydrophilic polymer. The optimized BER-LPHN exhibited a nanosize of 250–350 nm and a zeta potential of -25.00 ± 2.2 mV, with notably high drug loading (~ 87%). TEM analysis revealed the spherical morphology of the BER-LPHN, with the lipid coat surrounding the polymeric matrix, which facilitated controlled drug release from the polymeric core in vitro, resulting in an 18-fold increase in the oral bioavailability of berberine. In-vivo studies using fluorescently labeled nanoparticles demonstrated a significant concentration of BER-LPHN near the villi boundary and significant uptake by Peyer’s patches. Confocal microscopy further confirmed the lymphatic uptake of BER-LPHN through M cells of Peyer’s patches, suggesting that the formulated nanoparticles have the potential to enhance berberine's bioavailability by boosting permeability in the intestine via lymph transport.

Graphical Abstract

小檗碱是一种异喹啉类生物碱，因其结构多样性和广泛的生物活性而备受关注；然而，由于肠道吸收不良，其药理作用明显受到限制。本研究采用改进的纳米沉淀法制备脂质-聚合物混合纳米粒子（BER-LPHN），以提高小檗碱的生物利用度。采用32全因子设计优化配方，以磷脂90 H为脂质，甘特雷兹为亲水性聚合物。优化后的BER-LPHN纳米尺寸为250 ~ 350 nm， zeta电位为-25.00±2.2 mV，载药量高达87%。透射电镜分析显示，BER-LPHN呈球形，聚合物基质周围有一层脂质外壳，这有助于在体外控制药物从聚合物核心释放，从而使小檗碱的口服生物利用度提高18倍。使用荧光标记纳米颗粒的体内研究表明，在绒毛边界附近有显著浓度的BER-LPHN，并且被Peyer's斑块显著吸收。共聚焦显微镜进一步证实了通过Peyer’s patches的M细胞对BER-LPHN的淋巴吸收，这表明配方纳米颗粒有可能通过促进淋巴运输在肠道中的渗透性来提高小檗碱的生物利用度。

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引用次数: 0