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Keywords = SNEDDS formulation

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30 pages, 2238 KB  
Article
Preparation, Oral SNEDDS Formulation, and In Vivo Evaluation of the HIV-1 Latency-Reversing Agent EK-16A
by Lu Jin, Yuqi Zhu, Fan Yang, Ting Chen, Xinyi Yang, Yuan Tang, Yipeng Cheng, Dengji Zhang, Jingna Xun, Jun Liu, Bin Wang, Chunyu Li, Xingyu Wang, Suixiang Li, Xingwen Yu, Zhujian Wang, Yiping Zhang, Qian Zhong, Jianrong Ma, Jing Xue and Huanzhang Zhuadd Show full author list remove Hide full author list
Molecules 2026, 31(11), 1897; https://doi.org/10.3390/molecules31111897 - 1 Jun 2026
Viewed by 326
Abstract
Background/Objectives: AIDS is a serious threat to human health and remains incurable; however, EK-16A, an ingenol derivative, shows promise as a functional cure. In this study, we aimed to extract EK-16A from Euphorbia kansui, used in traditional Chinese medicine, to develop [...] Read more.
Background/Objectives: AIDS is a serious threat to human health and remains incurable; however, EK-16A, an ingenol derivative, shows promise as a functional cure. In this study, we aimed to extract EK-16A from Euphorbia kansui, used in traditional Chinese medicine, to develop an oral self-nanoemulsifying drug delivery system (SNEDDS) for EK-16A and evaluate it in vivo. Methods: EK-16A was purified by SFC combined with conventional extraction. The optimal SNEDDS formulation was selected by emulsification and stability testing. Pharmacokinetics, metabolomics, and proteomics were used for in vivo evaluation. Results: 1. The extraction yield of EK-16A was four times higher than that of the conventional process; the extraction scale was increased by 25 times, and the purity of EK-16A reached 98.0%. 2. EK-16A is a BCS Class IV compound with low solubility and permeability. The compound’s content degraded to 49.8% after 3 months at 25 °C/60% RH. The EK-16A SNEDDS formulation A#1 showed no degradation after 3 months at 40 °C/75% RH. The absolute bioavailability after oral administration of formulation A#1 in rats was 0.445%. 3. The proteomics results showed that EK-16A significantly downregulated the PI3K-AKT signaling pathway in SHIV-infected rhesus macaques. Specifically, all 11 identified differential proteins were significantly downregulated. Conclusions: 1. The extraction process for EK-16A features high yield, purity and large scale. 2. The SNEDDS formulation enhances the stability of EK-16A and successfully delivers this low-solubility and permeability compound into the systemic circulation. 3. Proteomics analysis revealed that EK-16A significantly downregulates the PI3K-AKT signaling pathway in SHIV-infected rhesus macaques. However, further experiments, such as measuring plasma viremia and cell-associated SHIV RNA, are needed to confirm this mechanism. Full article
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29 pages, 754 KB  
Review
Emerging Perspectives in the Formulation of Lyophilized Orally Disintegrating Tablets: From Lyoc to Self-Nanoemulsifying Lyophilized Tablets (SNELTs) and Beyond into Hybrid Platforms
by Eliza Grațiela Popa, Liliana Mititelu Tartau, Alina Diana Panainte, Larisa Păduraru and Andreea Crețeanu
Pharmaceutics 2026, 18(5), 615; https://doi.org/10.3390/pharmaceutics18050615 - 18 May 2026
Viewed by 553
Abstract
Four decades have elapsed since orally disintegrating tablets (ODTs) were first formulated as the emulsion/type Lyoc tablet, a porous mass intended to rapidly disperse in saliva. Following the lyophilization process, new formulations of ODTs were designed, intending to make a simpler and more [...] Read more.
Four decades have elapsed since orally disintegrating tablets (ODTs) were first formulated as the emulsion/type Lyoc tablet, a porous mass intended to rapidly disperse in saliva. Following the lyophilization process, new formulations of ODTs were designed, intending to make a simpler and more reproducible formulationZydis, LBL-Flash, Quicksolv, and, more recently, Zydis Ultra. Lyophilization is widely recognized as an effective technique for the development of ODTs, due to its ability to produce highly porous structures that enable rapid disintegration and improved patient compliance. However, its advantages should be considered in relation to other manufacturing methods, as each technology presents specific trade-offs in terms of cost, scalability, mechanical strength, drug loading capacity, and process robustness. In line with the modern sustainable and green pharmacy trend, new raw materials have gained attention as excipients for lyophilized ODTs; these materials include certain plant derivatives, but also performant excipients with newly discovered functionalities. At present, a new generation of ODTs is available in the form of Self-Nanoemulsifying Lyophilized Tablets (SNELTs), which bring the advantages of Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) into ODTs via the lyophilization method. The technique is mostly applicable to low-solubility drugs formulated as nanoemulsions, which are absorbed onto solid carriers and further lyophilized, forming the final ODT. Despite its limitations (expensive, time-consuming, and high product friability), lyophilization is being continuously developed nowadays, in combination with other techniques (3D printing, mucoadhesion, or electrospinning), building hybrid platforms for the modern ODTs of the future. Full article
(This article belongs to the Section Pharmaceutical Technology, Manufacturing and Devices)
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14 pages, 1686 KB  
Article
Solid Pro-Nano Lipid Oral Formulations for Cannabidiol (CBD)
by Awanish Kumar, Ayala Bar-Hai, Muhammad AbdEl-haq, Michal Gur, Amnon Hoffman and Abraham J. Domb
Pharmaceutics 2026, 18(4), 436; https://doi.org/10.3390/pharmaceutics18040436 - 31 Mar 2026
Viewed by 849
Abstract
Background: Solid pro-nano lipid (SPNL) oral formulations were prepared and tested in rats for enhanced oral bioavailability of cannabidiol (CBD). Methods: The solid formulation at room temperature is a uniform solution of CBD in a mixture of solid lipids and surfactants. [...] Read more.
Background: Solid pro-nano lipid (SPNL) oral formulations were prepared and tested in rats for enhanced oral bioavailability of cannabidiol (CBD). Methods: The solid formulation at room temperature is a uniform solution of CBD in a mixture of solid lipids and surfactants. Upon contact with aqueous media, it disperses into <200 nm particles. Up to 40% w/w of CBD can be loaded in this formulation into a hard gelatin capsule or mixed with solid additives and compressed into a tablet. Another type of SPNL formulation was prepared from the absorption of a liquid pro-nano lipid formulation onto a solid support, termed LPNL. Results: Pharmacokinetic studies on male Wistar rats (0.295–0.335 kg) reveals that a single oral dose of SPNL or LPNL leads to rapid CBD absorption and high Cmax values. The SPNL and LPNL formulations are stable at room temperature for at least 3 months. Powder forms of the SPNL and LPNL were prepared with Neusilin US2, SYLOID 244 FP, microcrystalline cellulose (Avicel PH 102), and mannitol. Both SPNL and LPNL show lesser stability for CBD with mesoporous silica particles such as Neusilin US2 and SYLOID 244 FP. Conclusions: The SPNL formulations do not contain any organic solvent and therefore are safer compared to the SNEDDS systems. These solid lipids-based oral formulations can be applied for the delivery of other lipophilic drugs. Full article
(This article belongs to the Special Issue Advances in Emulsifying Drug Delivery Systems)
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27 pages, 4674 KB  
Article
A Novel Drug Delivery System for the Treatment of Lupus Nephritis: From Delivery System Design and Optimization to Treatment
by Xumeng Xiong, Jin Tao, Zequn Jin and Ying Hu
Biomolecules 2026, 16(3), 476; https://doi.org/10.3390/biom16030476 - 23 Mar 2026
Viewed by 813
Abstract
Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE), characterized by immune system disorders and multiple organ damage. Current clinical treatment of LN requires a complex multi-drug combination, which is often associated with severe side effects and low patient compliance. [...] Read more.
Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE), characterized by immune system disorders and multiple organ damage. Current clinical treatment of LN requires a complex multi-drug combination, which is often associated with severe side effects and low patient compliance. The aim of this study was to design a self-nanoemulsifying drug delivery system (SNEDDS) co-loading total glucosides of Paeonia (TGP) and dihydroartemisinin (DHA) to increase the solubility of the drug as well as achieve synergistic anti-inflammatory and immunomodulatory effects for LN therapy. Network pharmacology, molecular docking and molecular dynamics simulations were employed to predict the core therapeutic targets and related signaling pathways. The SNEDDS co-loaded with TGP and DHA was optimized via central composite design response surface methodology (CCD-RSM). Its physicochemical properties, particle size and the polydispersity index (PDI) of the optimized formulation were characterized. In vivo therapeutic efficacy was evaluated in MRL/lpr mice by measuring disease-related indicators (urinary protein, serum ANA, and anti-ds-DNA) and inflammatory cytokines (TNF-α, IL-6, and IL-1β). Renal tissue pathology was also examined. All data were analyzed by one-way analysis of variance (ANOVA) with p < 0.05 considered statistically significant. The core therapeutic targets predicted with high relevance were AKT1, MAPK1, MAPK3, and RELA. The optimized SNEDDS achieved a high loading capacity of 16.11 ± 0.43 mg/g for TGP and 12.79 ± 1.33 mg/g for DHA, with a particle size of (25.84 ± 0.30) nm and PDI of (0.07 ± 0.02). In MRL/lpr mice, SNEDDS treatment significantly reduced urinary protein levels (p < 0.01), serum ANA (p < 0.01) and anti-ds-DNA titers (p < 0.01) compared with the model group. Additionally, the levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) were markedly decreased (p < 0.05), and renal tissue damage was alleviated. Conclusions: The SNEDDS co-loaded TGP and DHA is a promising oral nanotherapeutic strategy for LN, offering synergistic anti-inflammatory and immunomodulatory effects. Full article
(This article belongs to the Section Molecular Medicine)
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24 pages, 6041 KB  
Article
Formulation and Evaluation of Alginate Microcapsules Containing an Uncompetitive Nanomolar Dimeric Indenoindole Inhibitor of the Human Breast Cancer Resistance Pump ABCG2 with Different Excipients
by Krisztina Bodnár, Christelle Marminon, Florent Perret, Ádám Haimhoffer, Boglárka Papp, Pálma Fehér, Zoltán Ujhelyi, Joachim Jose, Marc Le Borgne, Ildikó Bácskay and Liza Józsa
Pharmaceutics 2025, 17(12), 1587; https://doi.org/10.3390/pharmaceutics17121587 - 9 Dec 2025
Cited by 1 | Viewed by 874
Abstract
Background/Objectives: The ABCG2 transporter actively effluxes anticancer drugs, reducing their efficacy and promoting multidrug resistance (MDR). Developing oral formulations of poorly soluble ABCG2 inhibitors remains challenging due to their low solubility and intestinal permeability. This study aimed to formulate and evaluate an [...] Read more.
Background/Objectives: The ABCG2 transporter actively effluxes anticancer drugs, reducing their efficacy and promoting multidrug resistance (MDR). Developing oral formulations of poorly soluble ABCG2 inhibitors remains challenging due to their low solubility and intestinal permeability. This study aimed to formulate and evaluate an ABCG2 inhibitor using micro- and nanoscale drug delivery systems. Methods: To address the poor solubility and bioavailability of the corresponding active ingredient, a self-nanoemulsifying drug delivery system (SNEDDS) was developed. The SNEDDS was encapsulated into microcapsules using sodium alginate crosslinked with calcium chloride. Five microcapsule formulations were developed, varying in the inclusion of polyvinylpyrrolidone (PVP), Transcutol® HP and SNEDDS. The effects of the excipients on encapsulation efficiency, swelling capacity, enzymatic stability, dissolution, cytocompatibility, and permeability were systematically evaluated. Results: The SNEDDS exhibited monodisperse particle sizes and efficient drug entrapment. Results revealed that formulations incorporating PVP and SNEDDS improved encapsulation efficiency and bioavailability. SNEDDS-containing formulations demonstrated superior enzymatic stability in simulated gastric and intestinal fluids and provided the highest cumulative drug release in vitro. Cytotoxicity studies conducted on Caco-2 and MCF-7 cells demonstrated that our formulations were well tolerated, indicating favorable biocompatibility. Conclusions: Our findings demonstrate that SNEDDS-loaded alginate microcapsules offer an efficient platform for oral delivery of dimeric ABCG2 inhibitors, combining enhanced solubility, stability, and controlled release. The optimized formulation can be regarded as a promising strategy to enhance the oral bioavailability of efflux pump inhibitors and other poorly soluble drugs. Full article
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23 pages, 7494 KB  
Article
Implementation of a Potential Industrial Green, Economical, and Safe Strategy to Enhance Commercial Viability of Liquid Self-Nanoemulsifying Drug Delivery System
by Abdelrahman Y. Sherif, Mohammad A. Altamimi and Ehab M. Elzayat
Pharmaceutics 2025, 17(11), 1461; https://doi.org/10.3390/pharmaceutics17111461 - 12 Nov 2025
Cited by 1 | Viewed by 1028
Abstract
Background/Objectives: Conventional solidification methods for liquid self-nanoemulsifying drug delivery systems face significant limitations. This includes complex manufacturing processes, high costs, and environmental concerns. This study aimed to develop and optimize a thermoresponsive self-nanoemulsifying drug delivery system (T-SNEDDS) for dapagliflozin as a sustainable [...] Read more.
Background/Objectives: Conventional solidification methods for liquid self-nanoemulsifying drug delivery systems face significant limitations. This includes complex manufacturing processes, high costs, and environmental concerns. This study aimed to develop and optimize a thermoresponsive self-nanoemulsifying drug delivery system (T-SNEDDS) for dapagliflozin as a sustainable alternative solidification technique. Methods: Oil and surfactant were selected based on solubility and emulsification studies. The Box–Behnken approach was used to examine the impacts of three independent variables (pluronic F127, propylene glycol, and dapagliflozin concentrations) on liquefying temperature and time. Optimized T-SNEDDS was characterized in terms of particle size, zeta potential, and dissolution performance. Stability assessment included centrifugation testing and a six-month storage evaluation. The green pharmaceutical performance was comparatively evaluated against five conventional solidification methods using ten adapted parameters. Results: Imwitor 308 and Cremophor EL were selected as optimal excipients for SNEDDS formulation. In addition, Pluronic F127 and propylene glycol were used to induce solidification during storage. The optimized formulation (8.60% w/w Pluronic F127, 10% w/w propylene glycol, and 5% w/w dapagliflozin) exhibited a liquefying temperature of 33.5 °C with a liquefying time of 100.3 s and a particle size of 96.64 nm. T-SNEDDS significantly enhanced dissolution efficiency of dapagliflozin (95.7%) compared to raw drug (42.4%) and marketed formulation (91.3%). Green pharmaceutical evaluation revealed that T-SNEDDS achieved the highest score compared to conventional approaches. Conclusions: T-SNEDDS represents a superior sustainable approach for SNEDDS solidification that offers enhancement in drug dissolution while addressing manufacturing, environmental, and economic challenges through its solvent-free and single-step preparation process with excellent scalability potential. Full article
(This article belongs to the Section Pharmaceutical Technology, Manufacturing and Devices)
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21 pages, 805 KB  
Review
Beyond Sleeping Disorders, the Role of Melatonin in Skin Diseases and Emerging Applications in Dermatology and Topical Therapy
by Jesus A. Simon, Celia Serrano, Dinesh Kumar, Brayan J. Anaya, Liliana Bautista, Carlos Torrado-Salmerón and Dolores R. Serrano
Gels 2025, 11(11), 860; https://doi.org/10.3390/gels11110860 - 27 Oct 2025
Cited by 2 | Viewed by 7438
Abstract
Melatonin, traditionally recognized for its role in regulating circadian rhythms and sleep, has emerged as a multifunctional molecule with significant implications in dermatology. Melatonin is described here as a pleiotropic, context-dependent modulator with antioxidant-related and immunomodulatory actions that are supported by both direct [...] Read more.
Melatonin, traditionally recognized for its role in regulating circadian rhythms and sleep, has emerged as a multifunctional molecule with significant implications in dermatology. Melatonin is described here as a pleiotropic, context-dependent modulator with antioxidant-related and immunomodulatory actions that are supported by both direct chemical scavenging in cell-free systems and indirect, enzyme-mediated effects in cells and tissues; its antitumor activity in dermatology is primarily preclinical and remains to be confirmed in large clinical trials. Melatonin protects skin cells from oxidative stress, UV radiation, and environmental damage by directly scavenging free radicals and activating endogenous defense systems. It also modulates immune responses, making it relevant in inflammatory dermatoses such as atopic dermatitis, while promoting tissue repair in wound healing and reducing signs of skin aging. Particular attention is given to topical formulations, including gels, creams, and patches, which enable localized delivery, improved skin penetration, and reduced systemic side effects. The review also discusses ongoing clinical trials, delivery technologies, and the potential for combinatorial therapies with established dermatological agents. Full article
(This article belongs to the Special Issue Advanced Hydrogels for Biomedical Applications)
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17 pages, 2562 KB  
Article
Comparative Stability and Anesthetic Evaluation of Holy Basil Essential Oil Formulated in SNEDDS and Microemulsion Systems in Cyprinus carpio var. Koi
by Kantaporn Kheawfu, Chuda Chittasupho, Surachai Pikulkaew, Wasana Chaisri and Taepin Junmahasathien
Pharmaceutics 2025, 17(8), 997; https://doi.org/10.3390/pharmaceutics17080997 - 31 Jul 2025
Cited by 2 | Viewed by 1150
Abstract
Background/Objectives: Holy basil (Ocimum tenuiflorum L.) essential oil exhibits antioxidant, antimicrobial, and anesthetic activities, mainly due to eugenol, methyl eugenol, and β-caryophyllene. However, its clinical application is limited by poor water solubility, instability, and low bioavailability. This study developed and compared two [...] Read more.
Background/Objectives: Holy basil (Ocimum tenuiflorum L.) essential oil exhibits antioxidant, antimicrobial, and anesthetic activities, mainly due to eugenol, methyl eugenol, and β-caryophyllene. However, its clinical application is limited by poor water solubility, instability, and low bioavailability. This study developed and compared two delivery systems, self-nanoemulsifying drug delivery systems (SNEDDS) and microemulsions (ME), to enhance their stability and fish anesthetic efficacy. Methods: The optimized SNEDDS (25% basil oil, 8.33% coconut oil, 54.76% Tween 80, 11.91% PEG 400) and ME (12% basil oil, 32% Tween 80, 4% sorbitol, 12% ethanol, 40% water) were characterized for droplet size, PDI, zeta potential, pH, and viscosity. Stability was evaluated by monitoring droplet size and PDI over time and by determining the retention of eugenol, methyl eugenol, and β-caryophyllene after storage at 45 °C. Fish anesthetic efficacy was tested in koi carp (Cyprinus carpio var. koi). Results: SNEDDS maintained a small droplet size (~22.78 ± 1.99 nm) and low PDI (0.188 ± 0.088 at day 60), while ME showed significant size enlargement (up to 177.10 ± 47.50 nm) and high PDI (>0.5). After 90 days at 45 °C, SNEDDS retained 94.45% eugenol, 94.08% methyl eugenol, and 88.55% β-caryophyllene, while ME preserved 104.76%, 103.53%, and 94.47%, respectively. In vivo testing showed that SNEDDS achieved faster anesthesia (114.70 ± 24.80 s at 120 ppm) and shorter recovery (379.60 ± 15.61 s) than ME (134.90 ± 4.70 s; 473.80 ± 16.94 s). Ethanol failed to induce anesthesia at 40 ppm and performed poorly compared to SNEDDS and ME at other concentrations (p < 0.0001). Conclusions: SNEDDS demonstrated superior physical stability and fish anesthetic performance compared to ME. These findings support SNEDDS as a promising formulation for delivering holy basil essential oil in biomedical and aquaculture applications. Full article
(This article belongs to the Special Issue Applications of Nanotechnology in Veterinary Drug Delivery)
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15 pages, 1743 KB  
Article
Development of Bioresponsive Poloxamer-Based Self-Nanoemulsifying System for Enhanced Febuxostat Bioavailability: Solidification Strategy Using I-Optimal Approach
by Abdelrahman Y. Sherif and Ehab M. Elzayat
Pharmaceutics 2025, 17(8), 975; https://doi.org/10.3390/pharmaceutics17080975 - 28 Jul 2025
Cited by 4 | Viewed by 1094
Abstract
Background/Objectives: The major limitations of self-nanoemulsifying systems include complex processing and expensive instrumentation required for solidification approaches. In this study, smart poloxamer-based solidification strategies were used to develop and optimize febuxostat-loaded formulations. Methods: A self-nanoemulsifying drug delivery system (SNEDDS) component was selected based [...] Read more.
Background/Objectives: The major limitations of self-nanoemulsifying systems include complex processing and expensive instrumentation required for solidification approaches. In this study, smart poloxamer-based solidification strategies were used to develop and optimize febuxostat-loaded formulations. Methods: A self-nanoemulsifying drug delivery system (SNEDDS) component was selected based on solubility and emulsification tests. The influence of poloxamer molecular weight (low or high) and its concentration (2–10% w/w) on formulation performance was assessed through the design of experiments. Finally, in-vitro melting assessment and a comparative dissolution test were performed on the optimized SNEDDS formulation. Results: Imwitor 988 and Tween 20 were selected to prepare the formulations. Increasing the molecular weight and concentration of the poloxamer significantly increased the temperature and time required for the melting of the SNEDDS formulation. The optimized SNEDDS formulation comprised 3.98% w/w poloxamer 188, which melts at 36 °C within 111 s. In-vitro melting showed that the formulation completely converted to a liquid state upon exposure to body temperature. Finally, the optimized SNEDDS formulation exhibited superior dissolution efficiency (96.66 ± 0.28%) compared to raw febuxostat (72.09 ± 4.33%) and marketed tablets (82.23 ± 3.10%). Conclusions: The poloxamer-based approach successfully addressed the limitations associated with conventional solidification while maintaining superior dissolution performance. Therefore, it emerges as a promising alternative approach for enhancing the bioavailability of poorly water-soluble drugs. Full article
(This article belongs to the Section Physical Pharmacy and Formulation)
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19 pages, 2810 KB  
Article
In Vitro Assessment of a Doubly Adjuvanted Self-Emulsified Nanoemulsion as a Delivery Vehicle for Antigenic Proteins
by Evgenia Tsanaktsidou, Maritsa Margaroni, Evdokia Karagouni, Costas Kiparissides and Olga Kammona
Pharmaceutics 2025, 17(7), 870; https://doi.org/10.3390/pharmaceutics17070870 - 2 Jul 2025
Cited by 2 | Viewed by 3796
Abstract
Background/Objectives: Leishmaniasis is a prevailing infectious disease transmitted via infected phlebotomine sandflies. The lack of an efficient vaccine with respect to immunogenic antigens and adjuvanted delivery systems impedes its control. Following the induction of immune responses in mice vaccinated with multi-epitope Leishmania peptides [...] Read more.
Background/Objectives: Leishmaniasis is a prevailing infectious disease transmitted via infected phlebotomine sandflies. The lack of an efficient vaccine with respect to immunogenic antigens and adjuvanted delivery systems impedes its control. Following the induction of immune responses in mice vaccinated with multi-epitope Leishmania peptides (LeishPts) encapsulated in doubly adjuvanted self-nanoemulsifying drug delivery systems (ST-SNEDDSs), this study aims to assess ST-SNEDDS-based nanoemulsions as vehicles for the delivery of antigenic proteins. Methods: Model antigens (e.g., BSA-FITC, OVA) were encapsulated in ST-SNEDDS after being complexed with the cationic phospholipid dimyristoyl phosphatidylglycerol (DMPG) via hydrophobic ion pairing. The nanoemulsions were characterized with respect to droplet diameter, zeta potential, stability, protein loading, protein release from the nanodroplets in different release media and cell uptake. Results: Both model antigens exhibited high encapsulation efficiency (>95%) and their release from the nanodroplets was shown to be strongly affected by the type of release medium (e.g., PBS, FBS 10% v/v) and the ratio of its volume to that of the oily phase, in agreement with predictions of protein release. Protein-loaded nanoemulsion droplets labeled with Cy-5 were found to be efficiently taken up by macrophages (J774A.1) in vitro. However, no colocalization of the labeled nanodroplets and BSA-FITC could be observed. Conclusions: It was revealed that in contrast with LeishPts, whole protein molecules may not be appropriate antigenic cargo for ST-SNEDDS formulations due to the rapid protein release from the nanodroplets in release media simulating in vitro culture and in vivo conditions such as FBS 10% v/v. Full article
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47 pages, 1349 KB  
Review
Quality by Design and In Silico Approach in SNEDDS Development: A Comprehensive Formulation Framework
by Sani Ega Priani, Taufik Muhammad Fakih, Gofarana Wilar, Anis Yohana Chaerunisaa and Iyan Sopyan
Pharmaceutics 2025, 17(6), 701; https://doi.org/10.3390/pharmaceutics17060701 - 27 May 2025
Cited by 19 | Viewed by 4522
Abstract
Background/Objectives: The Self-Nanoemulsifying Drug Delivery System (SNEDDS) has been widely applied in oral drug delivery, particularly for poorly water-soluble compounds. The successful development of SNEDDS largely depends on the precise composition of its components. This narrative review provides an in-depth analysis of [...] Read more.
Background/Objectives: The Self-Nanoemulsifying Drug Delivery System (SNEDDS) has been widely applied in oral drug delivery, particularly for poorly water-soluble compounds. The successful development of SNEDDS largely depends on the precise composition of its components. This narrative review provides an in-depth analysis of Quality by Design (QbD), Design of Experiment (DoE), and in silico approach applications in SNEDDS development. Methods: The review is based on publications from 2020 to 2025, sourced from reputable scientific databases (Pubmed, Science direct, Taylor and francis, and Scopus). Results: Quality by Design (QbD) is a systematic and scientific approach that enhances product quality while ensuring the robustness and reproducibility of SNEDDS, as outlined in the Quality Target Product Profile (QTPP). DoE was integrated into the QbD framework to systematically evaluate the effects of predefined factors, particularly Critical Material Attributes (CMAs) and Critical Process Parameters (CPPS), on the desired responses (Critical Quality Attributes/CQA), ultimately leading to the identification of the optimal SNEDDS formulation. Various DoEs, including the mixture design, response surface methodology, and factorial design, have been widely applied to SNEDDS formulations. The experimental design facilitates the analysis of the relationship between CQA and CMA/CPP, enabling the identification of optimized formulations with enhanced biopharmaceutical, pharmacokinetic, and pharmacodynamic profiles. As an essential addition to this review, in silico approach emerges as a valuable tool in the development of SNEDDS, offering deep insights into self-assembly dynamics, molecular interactions, and emulsification behaviour. By integrating molecular simulations with machine learning, this approach enables rational and efficient optimization. Conclusions: The integration of QbD, DoE, and in silico approaches holds significant potential in the development of SNEDDS. These strategies enable a more efficient, rational, and predictive formulation process. Full article
(This article belongs to the Section Pharmaceutical Technology, Manufacturing and Devices)
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21 pages, 7194 KB  
Article
Quality by Design (QbD)-Based Development of a Self-Nanoemulsifying Drug Delivery System for the Ocular Delivery of Flurbiprofen
by Ju-Hwan Jeong, Tae-Han Yoon, Si-Won Ryu, Min-Gyeong Kim, Gu-Hae Kim, Ye-Jin Oh, Su-Jeong Lee, Na-Woon Kwak, Kyu-Ho Bang and Kyeong-Soo Kim
Pharmaceutics 2025, 17(5), 629; https://doi.org/10.3390/pharmaceutics17050629 - 9 May 2025
Cited by 4 | Viewed by 1992
Abstract
Objectives: In this study, Quality by Design (QbD) was used to develop an optimized self-nanoemulsifying drug delivery system (SNEDDS) as an ophthalmic formulation of flurbiprofen (FLU). Using a Box–Behnken design (BBD), an optimal SNEDDS composition was crafted, targeting enhanced corneal permeability and [...] Read more.
Objectives: In this study, Quality by Design (QbD) was used to develop an optimized self-nanoemulsifying drug delivery system (SNEDDS) as an ophthalmic formulation of flurbiprofen (FLU). Using a Box–Behnken design (BBD), an optimal SNEDDS composition was crafted, targeting enhanced corneal permeability and increased bioavailability of the drug. Methods: The levels of each factor(X) were established using a pseudo-ternary diagram, and the Box-Behnken design (BBD) was used to evaluate the components of oil (18.9 mg), surfactant (70.7 mg), and co-surfactant (10.0 mg) to optimize the SNEDDS formulation. The response(Y) considered were particle size, polydispersity index (PDI), transmittance, and stability. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) were used to analyze the particle size and morphology. In vitro and ex vivo diffusion tests were conducted to assess drug flux and permeability. Result: Using a response optimization tool, the values of each X factor were optimized to achieve a small particle size (nm), a low polydispersity index (PDI), and high transmittance (%), resulting in a formulation prepared with 18.9 mg of oil, 70.7 mg of surfactant, and 10.0 mg of co-surfactant. The optimized SNEDDS exhibited a small particle size of 24.89 nm, a minimal PDI of 0.068, and a high transmittance of 74.85%. A transmission electron microscopy (TEM) analysis confirmed the presence of uniform spherical nanoemulsion droplets with an observed mean diameter of less than 25 nm, corroborating the dynamic light scattering (DLS) measurements. Furthermore, the SNEDDS demonstrated improved stability under the stress conditions of heating–cooling cycles, with no phase separation, creaming, or caking observed and no differences in its particle size, PDI, or transmittance. In vitro and ex vivo diffusion tests demonstrated that the flux of the optimized SNEDDS (2.723 ± 0.133 mg/cm2, 5.446 ± 0.390 μg/cm2) was about 2.5 and 4 times higher than that of the drug dispersion, and the initial diffusion was faster, which is suitable for the characteristics of eye drops. Conclusions: Therefore, the formulation of a flurbiprofen-loaded SNEDDS (FLU-SNE) was successfully optimized using the QbD approach. The optimized FLU-SNE exhibited excellent stability and enhanced permeability, suggesting its potential effectiveness in treating various ocular inflammations, including uveitis and cystoid macular edema. Full article
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27 pages, 4743 KB  
Article
Bioavailability for the Improved Therapeutic Profile of trans-Dehydrocrotonin Incorporated into a Copaiba Oil Self-Nanoemulsifying Drug Delivery System: Formulation, Physicochemical Characterizations, and Antioxidant In Vitro Effect
by José Robério de Oliveira Netto, Natália Pignataro Corrêa, Leonardo Bruno Aragão de Araujo, Weslley de Souza Paiva, Hugo Alexandre Oliveira Rocha, Waldenice de Alencar Morais Lima, José Heriberto Oliveira do Nascimento, Daniel Charles dos Santos Macedo, Nereide Stela Santos-Magalhães, Valdir Florêncio da Veiga Júnior and Maria Aparecida Medeiros Maciel
Int. J. Mol. Sci. 2025, 26(10), 4469; https://doi.org/10.3390/ijms26104469 - 8 May 2025
Cited by 2 | Viewed by 1841
Abstract
Croton cajucara Benth and Copaifera reticulata Ducke are prominent species in the traditional medicine of the Amazon region of Brazil. Copaifera species produce oil resin rich in bioactive diterpenes, and C. cajucara is a prolific producer of the diterpene 19-nor-clerodane trans [...] Read more.
Croton cajucara Benth and Copaifera reticulata Ducke are prominent species in the traditional medicine of the Amazon region of Brazil. Copaifera species produce oil resin rich in bioactive diterpenes, and C. cajucara is a prolific producer of the diterpene 19-nor-clerodane trans-dehydrocrotonin (t-DCTN). This research aimed to develop a self-nanoemulsion drug delivery system (SNEDDS) by using copaiba oil resin (C. reticulata) as a carrier for t-DCTN. A stable SNEDDS single-phase nanoemulsion comprising Tween 80 (7%, w/w) and copaiba oil (0.5%, w/w) afforded a fine oil-in-water carrier system (SNEDDS-CO). The dropwise solubilization of t-DCTN (1 mg) into SNEDDS-CO resulted in the nanoformulation called SNEDDS-CO-DCTN. Transmission electron microscopy (TEM) analysis revealed spherical nanodevices, while particle size, polydispersity index (PDI), and zeta potential measurements indicated small nanodroplets (about 10 nm), uniformly distributed (between 0.1 and 0.2) and negatively charged for both systems. The in vitro kinetic of t-DCTN-loaded (SNEDDS-CO-DCTN) analyzed by using simulated conditions of the gastrointestinal microenvironment, as perspective for oral drug delivery, showed a controlled release profile, and corresponded to the Fickian diffusion model. The in vitro antioxidant activity of the samples (t-DCTN, SNEDDS-CO, and SNEDDS-CO-DCTN) was confirmed through total antioxidant capacity (TAC), reducing power, copper ion chelation, and hydroxyl radical scavenging assays. The antioxidant activity of SNEDDS-CO-DCTN which contained 1 mg of t-DCTN per mL−1 of the carrier SNEDDS-CO was similar or even better when compared to the unload t-DCTN solubilized in DMSO (10 mg mL−1). The SNEDDS formulations herein described were successfully obtained under moderated and controlled conditions, exhibiting effective physicochemical data and release characteristics with huge bioaccessibility for co-loading copaiba oil and t-DCTN. The novel colloidal system SNEDDS-CO-DCTN is a potential antioxidant nanoproduct and, from now on, is available for further pharmacological investigations. Full article
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17 pages, 5983 KB  
Article
Development of Herbal Mouthwash Powder Using a Self-Nanoemulsifying Drug Delivery System Containing Galangal Extract and Lemongrass Oil for Oral Candidiasis Treatment
by Premnapa Sisopa, Supaporn Lamlertthon, Ruchadaporn Kaomongkolgit, Pratthana Chomchalao and Waree Tiyaboonchai
Pharmaceutics 2025, 17(5), 546; https://doi.org/10.3390/pharmaceutics17050546 - 23 Apr 2025
Cited by 5 | Viewed by 3035
Abstract
Objective: This study aimed to develop and characterize the physicochemical properties of a self-emulsion drug delivery system (SNEDDS) incorporating galangal extract (GE) and lemongrass oil (LGO). Then, to develop mouthwash powders containing GE- and LGO-loaded SNEDDS (GL-mouthwash powder) as a promising alternative for [...] Read more.
Objective: This study aimed to develop and characterize the physicochemical properties of a self-emulsion drug delivery system (SNEDDS) incorporating galangal extract (GE) and lemongrass oil (LGO). Then, to develop mouthwash powders containing GE- and LGO-loaded SNEDDS (GL-mouthwash powder) as a promising alternative for preventing and treating denture stomatitis. Methods: The solubility of GE in various vehicles was determined. Subsequently, pseudo-ternary phase diagrams of the different ingredients, oil (LGO), surfactant (Tween® 80), and co-surfactant (Propylene glycol) were selected to develop the SNEDDS. Then, SNEDDS containing GE and LGO (GL-SNEDDS) were prepared and characterized. The optimized liquid GL-SNEDDS was transformed into GL-mouthwash powder by absorbing onto mannitol and blending with a sweetener. Subsequently, various evaluations including drug recovery, moisture content, emulsification time, stability, anti-Candida activity, and in vitro cytotoxicity were performed. Results: The developed SNEDDS formulation improved GE and LGO solubility. The optimized GL-SNEDDS exhibited a small droplet size of 148.2 ± 2.1 nm with a polydispersity index of 0.11 ± 0.03 and a zeta potential of 2.14 ± 0.11 mV. In addition, the GL-mouthwash powder demonstrated a high drug recovery of >80% with a low moisture of <10% and exhibited greater physicochemical stability under accelerated conditions. The developed GL-mouthwash powder rapidly formed a stable nanoemulsion within 2 min after reconstitution. Interestingly, GL-mouthwash powder exhibited strong anti-Candida activity with no toxicity to human fibroblast cells, which demonstrated superior biocompatibility relative to existing commercial products. Conclusions: These findings suggest that GL-mouthwash powder has potential as an alternative prevention and treatment of oral Candida infection. Full article
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28 pages, 6588 KB  
Article
Formulation and Evaluation of Solid Self-Nanoemulsifying Drug Delivery System of Cannabidiol for Enhanced Solubility and Bioavailability
by Fengying Wu, Qing Ma, Guanghui Tian, Kaixian Chen, Rulei Yang and Jingshan Shen
Pharmaceutics 2025, 17(3), 340; https://doi.org/10.3390/pharmaceutics17030340 - 6 Mar 2025
Cited by 16 | Viewed by 7809
Abstract
Background/Objectives: This study aims to develop a solid self-nanoemulsifying drug delivery system (SNEDDS) to enhance the solubility and oral bioavailability of cannabidiol (CBD). Methods: According to the solubility of CBD and pseudo-ternary phase diagrams of the different ingredients, an oil (medium-chain triglyceride, MCT), [...] Read more.
Background/Objectives: This study aims to develop a solid self-nanoemulsifying drug delivery system (SNEDDS) to enhance the solubility and oral bioavailability of cannabidiol (CBD). Methods: According to the solubility of CBD and pseudo-ternary phase diagrams of the different ingredients, an oil (medium-chain triglyceride, MCT), mixed surfactants (Labrasol, Tween 80), and a co-surfactant (Transcutol) were selected for the SNEDDS. CBD-loaded SNEDDS formulations were prepared and characterized. The optimal SNEDDS was converted into solid SNEDDS powders via solid carrier adsorption and spray drying techniques. Various evaluations including flowability, drug release, self-emulsifying capacity, X-ray diffraction (XRD), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), morphology, and pharmacokinetic characteristics were conducted. Subsequently, the solid powders with fillers, disintegrants, and lubricants were added to the capsules for accelerated stability testing. Results: The investigations showed that the two S-SNEDDS formulations improved the CBD’s solubility and in vitro drug release, with good storage stability. The pharmacokinetic data of Sprague Dawley rats indicated that a single oral dose of L-SNEDDS and spray drying SNEDDS led to a quicker absorption and a higher Cmax of CBD compared to the two oil-based controls (CBD-sesame oil (similar to Epidiolex®) and CBD-MCT), which is favorable for the application of CBD products. Conclusions: SNEDDS is a prospective strategy for enhancing the solubility and oral bioavailability of CBD, and solid SNEDDS offers flexibility for developing more CBD-loaded solid formulations. Moreover, SNEDDS provides new concepts and methods for other poorly water-soluble drugs. Full article
(This article belongs to the Section Physical Pharmacy and Formulation)
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