Aug 2026· Food Chemistry· Vol 526, pp.
150653
· 0 citations· 32 references
Medicine
Abstract
Supersaturation improves the apparent solubility of lipophilic nutraceuticals but is constrained by crystallization and limited stability. This study elucidates how interfacial molecular organization in microemulsions governs curcumin supersaturation stabilization. An optimal supersaturation degree (50-200-fold) was identified, within which over 80% of the initial supersaturation was preserved during storage and upon gastrointestinal dilution, whereas excessive loading (300-fold) triggered crystallization and loss of metastability. 1H NMR analysis revealed progressive upfield shifts of Tween 80 α1-CH2/α2-CH2 protons, accompanied by perturbations in curcumin aromatic and olefinic signals, indicating preferential localization within the spatially confined interfacial layer. This interfacial partitioning likely restricts molecular mobility and suppresses nucleation. Functionally, microemulsions enhanced intestinal transport and bioavailability of curcumin. Bioavailability increased within the 50-200-fold range but declined at higher supersaturation due to aggregation during digestion. This work establishes a structure-function relationship between interfacial organization and supersaturation stability, providing a rational basis for designing high-performance delivery systems for lipophilic bioactives.
Abstract Self-microemulsifying drug delivery systems (SMEDDS) containing volatile phytotherapeutics such as thymol (T), carvacrol (C), and eugenol (E) present significant formulation challenges, even when solidified. Their instability and interactions with coatings often hinder intestinal delivery. To address these limitations, we developed solid SMEDDS consisting of pellets (microcrystalline cellulose/magnesium aluminometasilicate/chitosan) and enteric capsules (CEC) for enhanced intestinal delivery. Based on solubility and pseudo-ternary phase diagrams, SMEDDS formulations (SES1-3) differing in component ratios (glycerol monooleate/caprylocaproyl macrogol-8 glycerides/diethylene glycol monoethyl ether) with 5% w/w of each drug were identified, demonstrating nano-scale droplet sizes (PDI <0.4) and showing no phase separation over 6 months. Thermodynamic stability and liquid-state NMR revealed particle size variations with preserved structural integrity. The lead formulation SES1 exhibited superior ex-vivo intestinal permeation (T-SES1). CECs filled with T-, C-, and E-loaded SES1 pellets, respectively, prepared via extrusion/spheronization, exhibited in-vitro gastro-resistant release, and achieved > 85% drug release within 120 min after a pH change to 6.8 during a one-year stability study (25 °C; 60% RH). FTIR-ATR analysis of the CEC internal surface confirmed the temperature-dependent restructuring of hypromellose and E sorption, a phenomenon not observed with C or T, which is likely attributable to physicochemical distinctions. Oral administration of CEC with T-SES1-pellets (0.5 mg/kg) in piglets demonstrated a delayed peak plasma concentration (Cmax 11.67 ng/mL at 9 h) and sustained systemic exposure (AUC 119.8 ng·h/mL). These in-vivo findings substantiate the gastro-protective effect and enhanced intestinal absorption, positioning the pellet/CEC system as a promising strategy for the application of volatile phytotherapeutics in current pharmacotherapy.
Gabriela Koutná, Jan Kotouček, Jan Macků et al.· Drug Delivery· 0 citations
In conventional miniemulsion polymerization, stabilized miniemulsion droplets serve as individual sites for polymer particle formation. The present study shows that the cosurfactants linalool (LO) and benzyl acetate (BAc) follow distinct molecular redistribution pathways in templating miniemulsion, thus redirecting nucleation during copolymerization. In the studied miniemulsion copolymerization of styrene (St) and a highly hydrophobic high oleic soybean oil-based acrylic monomer (HOSBM), LO and BAc were used in combination with sodium dodecyl sulfate (SDS). Replacing up to 70 wt % of the SDS with BAc resulted in successful latex formation, high monomer conversion, and monomodal particle size distribution. In contrast, increasing LO fractions led to reduced conversion, increased coagulum formation, and bimodal latex particle distribution. Assessment of the apparent interfacial activity of LO and BAc in model systems revealed hidden redistribution pathways depending on the mixing regime with the St phase. LO likely provides spontaneous compartmentalization of St within aqueous domains. These interactions are consistent with hydrotrope-like behavior, which promotes the formation of competing nucleation sites. In contrast, upon mechanical agitation BAc partitioned preferentially into the St-rich phase, supporting droplet-templated polymerization. The experimental strategy presented here provides a framework for resolving competing molecular interactions and redistribution pathways in evolving emulsion systems.
Z. Demchuk, Tetiana Shevtsova, Bohdan Domnich et al.· Langmuir· 0 citations
The development of stable, high-concentration oil-in-water nanoemulsions (NEs) incorporating thyme essential oil (TEO) is hindered by intrinsic instability mechanisms, such as Ostwald ripening, and by challenges in characterizing concentrated, optically complex systems. Here, a rational, inquiry-driven formulation strategy, aligned with Formulation by Design principles, was applied to produce NEs containing 25% w/w oil phase. By systematically evaluating surfactant type, HLB, and the incorporation of neem oil as a ripening inhibitor, three stable formulations (TT80, TNT80, and TL) were obtained with reduced surfactant content and enhanced structural stability. Dilution effects were investigated using DLS, NTA, and small-angle X-ray scattering (SAXS), demonstrating that conventional characterization techniques may introduce artifacts when applied to highly concentrated systems without accounting for compositional and structural changes. Dilution tests elucidated the transition from concentrated to diluted states, providing insight into measurement constraints an4d potential application scenarios. Among the tested systems, TL exhibited the highest structural resistance upon dilution. Ecotoxicological assessment using Scenedesmus sp. and Daphnia magna revealed species-specific and endpoint-dependent responses, underscoring the importance of a multi-species approach for environmental risk evaluation. At concentrations below 10 mg/L, the NEs showed minimal ecological impact, suggesting that the formulations could be effective while remaining environmentally safe, thus supporting their potential use in multiple fields, including pharmaceutical applications aligned with green pharmacy principles, as well as food and agricultural sectors, such as compost biostabilisation. Overall, this work establishes a methodological and application-oriented framework for the rational design of concentrated, environmentally conscious NEs, and provides new insights into the relationships between formulation composition, nanostructure, stability, and ecotoxicological behavior.
Maria Gioia Fabiano, E. D’Intino, F. R. Stacchini et al.· International journal of pha...· 0 citations
Lapatinib (LPT), a brick-dust kinase inhibitor, shows slow oral bioavailability and dose-limiting gastrointestinal side effects that frequently lead to therapeutic discontinuation. Increasing oral bioavailability does not mitigate these adverse effects, and developing complex LPT delivery systems is challenging due to its poor solubility in organic or lipid solvents. Here, we identified a synergistic lipid-surfactant nanoemulsion system comprising Miglyol 812-oleic acid (1:1) oil phase, Solutol HS-15-TPGS (1:2) surfactant, and PEG-400 cosurfactant as a solubilization space for LPT and formulated it into a nanoemulsion delivery system (MIOL-NE). Phase analyses and Box-Behnken (BBD) optimization yielded MIOL-NE size (117 nm) suitable for parenteral administration. Stable LPT-loaded MIOL-NE (10 mg/g) was subsequently prepared (LPT-MIOL-NE). In vitro release in the presence and absence of lipase indicated mixed diffusion- and digestion-governed kinetics for LPT from the NE. LPT-MIOL-NE showed a more selective cytotoxicity (MDAMB-231 to NKE and HEK-293 cells) than LPT suspension, while preserving downstream effects of tyrosine kinase inhibition and suppression of cell invasion. Pharmacokinetic evaluation in Wistar rats revealed 2.4-times higher Cmax and 5.3-times higher AUC0-24 for intraperitoneally administered LPT-MIOL-NE than for the LPT suspension. In 4T1-bearing orthotopic BALBc nude mice, LPT-MIOL-NE at a 6 mg/kg i.m. dose reduced tumor volumes to90 mm3 (82 mm3 with i.p.) compared to 120 mm3 in control animals during the 21-day intervention. The results establish that NE can enhance the efficacy of LPT following i.m./i.p administration and open the scope for future investigations to delineate the contribution of colloidal uptake to post-digestive molecular transport in determining drug absorption from i.m./i.p-administered nanoemulsion (NE).
Nidhi Singh, Satyajit Halder, Alok Kumar et al.· Colloids and Surfaces B: Bio...· 0 citations
This review aims to compare recent nanocarrier systems for β-carotene delivery, emphasizing their capacity to enhance stability, bioaccessibility and bioavailability.
A structured search of Web of Science and PubMed identified peer reviewed English articles published from 2020 to 2025, supplemented by earlier key reports. Search terms combined “β-carotene” with relevant delivery and performance indicators.
Nanoemulsions favor rapid lipolysis and micellization, whereas liposomes and polymeric or lipid nanoparticles provide stronger protection and tunable release at the cost of greater complexity. Performance depends on oil digestibility, interfacial properties and enzymatic accessibility. Reported bioaccessibility varies widely due to methodological differences; in vivo evidence remains limited. No universal carrier exists. Selection should be based on the target matrix, processing conditions, release site and regulatory context, with a clear distinction between in vitro bioaccessibility and in vivo bioavailability.
Progress relies on harmonized digestion protocols, direct carrier comparisons, scalable production, safety evaluation, transparent labeling and stronger correlations between in vitro performance and in vivo outcomes.
Ruotong Han, Wancong Yu, Xiaohong Kou et al.· Nutrition & Food Science· 0 citations
Abstract Objective To evaluate formulation enabling technologies for improving bioavailability of a poorly water-soluble, weakly basic compound with inherent chemical stability challenges. Significance While exposure enhancement is a key objective in developing poorly soluble compounds, chemical stability liabilities may be overlooked during technology screening. A balanced assessment of pharmacokinetics (bioavailability) and stability is critical for successful formulation development. Methods Initial screening evaluated pH modification, lipid-based formulation (LBF), and amorphous solid dispersion (ASD) technologies. Stability and pharmacokinetic (PK) performance were assessed in dogs and compared with conventional crystalline formulation. Due to chemical stability challenges, additional technology screening using nanosizing and cyclodextrin complexation was conducted. Chemical stability studies were performed under accelerated conditions (40 °C/75%RH). Results The pH-modified formulation showed no PK improvement. LBF and ASD provided a 40–50% increase in AUC0–24, indicating enhanced exposure in the amorphous state. However, all three approaches exhibited chemical degradation, with LBF showing >25% degradation after 3 weeks at 40 °C/75%RH. The addition of antioxidants did not improve stability. Nanosizing and cyclodextrin complexation resulted in >2-fold increases in Cmax and AUC0–24. Importantly, both approaches demonstrated excellent chemical stability under accelerated conditions. Conclusions Although LBF and ASD improved PK exposure, chemical instability limited their suitability. Nanosizing and cyclodextrin complexation provided superior bioavailability enhancement with robust stability, highlighting the importance of simultaneously optimizing exposure and chemical stability during formulation development.
Stephie Lee, Preetanshu Pandey· Drug Development and Industr...· 0 citations
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