Search Results (68)

Background/Objectives: Clonazepam (CLZ), a BCS Class II drug, presents significant oral delivery challenges due to its low aqueous solubility. This study explores the systematic development of solid self-emulsifying drug delivery systems (S-SEDDS) using Quality by Design (QbD). The primary objective was to evaluate and compare advanced mathematical optimization frameworks, specifically Derringer’s Desirability Function (D) and Weighted Goal Programming (WGP), to identify a robust formulation that enhances drug solubilization while ensuring superior processability and flowability. Methods: Liquid SEDDS were solidified by adsorption onto a porous matrix (Aerosil^® 200/Lactose). A multi-objective optimization was conducted to define a robust Design Space (DS), comparing D against WGP. The trade-offs between competing Critical Quality Attributes (CQAs), specifically powder flowability (angle of repose, AR), blending efficiency (BE), and CLZ recovery (CR), were evaluated. Characterization included morphology from Environmental Scanning Electron Microscopy (ESEM), droplet size analysis, and pH-dependent dissolution studies. Results: D provided a highly robust baseline, yielding constant optimal coordinates (F2, F3 = +1; F4 = 0) across all sensitivity levels, with a predicted AR of 40.46°, BE of 0.12 and CR of 90.0%. However, WGP successfully refined this solution by allowing a more flexible weighting of goals, achieving a more favorable compromise with an AR of 38.96°, a BE of 0.11, and a CR of 90.23%. The optimized system maintained nanometric droplet sizes (<200 nm) and showed a controlled, pH-independent release profile, reaching 80% drug solubilization at 6 h. Conclusions: Integrating WGP into the QbD framework offers a more versatile and precise optimization than the traditional D for complex pharmaceutical systems. This approach ensures the production of high-quality S-SEDDS, bridging the gap between mathematical modeling and the stringent requirements of industrial solid dosage manufacturing. Full article

Background: The oral delivery of biopharmaceuticals remains a major challenge for researchers and the pharmaceutical industry. Therefore, extensive research is ongoing to develop a viable delivery method, hence self-emulsifying drug delivery systems (SEDDSs) are being investigated because of their ability to protect the carried macromolecules in the gastrointestinal environment and facilitate absorption through the intestinal barrier. Objectives: To systematically investigate this promising method for the oral delivery of lysozyme (LYZ) and to model oral peptide/protein administration. Methods: LYZ/sodium dodecyl sulfate (SDS) hydrophobic ion pairs (HIPs) were prepared to enhance protein solubility and stability in SEDDSs. Different surfactants (Tween^® 20 and 80) and as co-surfactants (Span^® 20 and 80) were combined for the preparation of liquid SEDDSs according to a 2² full factorial design and samples of each combination were formulated based on a three-factor-constrained mixture design. The critical quality attributes (CQAs), droplet size, polydispersity index (PDI), and zeta potential were measured by dynamic light scattering (DLS). The process design space was determined by response surface methodology (RSM) and two-dimensional ternary contour plots. An in vitro release test was performed using the sample-and-separate approach. Results: Emulsions of SEDDSs with the optimal properties of droplet size < 200 nm, PDI < 0.4 and zeta potential < −10 mV were prepared. Consequently, a HIP load of 10 mg/g was achievable, exhibiting apparent first-order kinetics, with approximately 80% of the loaded LYZ released within 6 h. Conclusions: This study may contribute to better understanding of the effects and interactions of formulating materials for SEDDSs and their possible role in the oral delivery of biopharmaceuticals. Full article

This study evaluated two formulations of L-carnitine, which were developed and impregnated in an oil-based self-emulsifying system (SEDDS), the first with tyrphostin AG17 and the second without the addition of tyrphostin AG17. The formulation with tyrphostin AG17 showed the presence of stable microvesicles up to 498 h after its preparation. To establish a robust safety profile in compliance with modern regulatory frameworks and the 3Rs principle (replacement, reduction, and refinement), a toxicological evaluation was conducted integrating an in silico quantitative structure–activity relationship (QSAR) analysis with confirmatory in vivo subchronic toxicity studies. The QSAR analysis, performed using the OECD QSAR Toolbox and strictly adhering to Organization for Economic Co-operation and Development (OECD) validation principles, predicted an acute oral LD50 of 91.5 mg/kg in rats, a value showing high concordance with the historical experimental data (87 mg/kg). Furthermore, computational modeling for repeated-dose toxicity yielded a no-observed-adverse-effect level (NOAEL) of 80.0 mg/kg bw/day, a no-observed-effect level (NOEL) of 60.4 mg/kg bw/day, and an ADI = 56 mg/day. These computational findings were substantiated by a 90-day subchronic toxicity study in male Wistar rats, where daily intragastric administration of tyrphostin AG17 at doses up to 1.75 mg/kg resulted in not statistically significant hematotoxic activity (p < 0.05), with a maximum cumulative dose over 90 days of 157.5 mg/kg. Collectively, these data indicate that tyrphostin AG17 combines high stabilizing efficacy with a manageable safety profile, supporting its proposed regulatory status as a functional food additive. Based on these results, it is concluded that tyrphostin AG17 shows promising characteristics for use as a stabilizer in food and other substances. Full article

Cannabidiol (CBD) is a non-psychoactive phyto-cannabinoid with numerous pharmacological potentials. CBD is a lipophilic drug with poor and varied bioavailability due to its low water solubility and extensive first-pass metabolism, and it is highly affected by the presence of food. A self-emulsifying drug delivery system (SEDDS) was developed to improve the aqueous solubility and oral bioavailability of CBD. The formulation strategy involved incorporating excipients that maintain drug solubility under both fasted and fed conditions, while potentially mitigating first-pass metabolism to enhance overall bioavailability and dose proportionality. Caproyl^® 90, Tween^® 20, and Transcutol^® HP were selected as the oil phase, surfactant, and cosolvent, respectively, for formulation preparation and screening. CBD SEDDS formulations containing Caproyl^® 90 ≤20% w/w and Tween^® 20 above 40% w/w yield particles below 200 nm. CBD SEDDS with Tween^® 20 65% w/w or higher showed in vitro release of more than 90%. After in vitro digestion, CTT1, CTT4, and CTT8 remained stable under gastrointestinal conditions and maintained CBD solubility of at least 50%. The most promising formulations, CTT4 and CTT8, were used for in vivo evaluations. Both formulations showed similar in vitro results; however, in vivo, CTT4 demonstrated 2.4-fold higher bioavailability than CTT8. Overall, optimizing the level of inhibitory surfactant appears to be a promising strategy for improving CBD bioavailability. Full article

Ophthalmic drug delivery encounters unique challenges due to the anatomical and physiological ocular barriers, necessitating the development of novel drug delivery systems (NDDSs). This review focuses on emerging therapeutic platforms, including nanoemulsions (NEs), microemulsions (MEs), self-emulsifying drug delivery systems (SEDDSs) such as self-nano emulsifying drug delivery systems (SNEDDSs) and self-micro emulsifying drug delivery systems (SMEDDSs), emulgels, and in situ-forming emulgels, as novel strategies for enhancing ocular drug delivery. NEs and MEs, due to their small globule size, excellent drug solubility, stability, and bioavailability, offer promising solutions for effective ocular therapy. SEDDSs further enhance the stability and bioavailability of hydrophobic drugs through self-emulsification in aqueous environments. Emulgels, combining the benefits of emulsions and gels, provide sustained and controlled release of therapeutic agents, improving the ocular retention time and therapeutic efficacy. Additionally, in situ-forming emulgels offer the advantage of liquid-to-gel transition upon contact with ocular surfaces, optimizing drug delivery. The review discusses various ocular diseases, challenges for ocular delivery of conventional formulations, updates on emulsion-based novel drug delivery systems for ophthalmic drug delivery, mechanisms of enhanced ocular permeation, formulation strategies, advantages, and challenges, design-of-experiment considerations for optimization, characterizations, and recent advancements in these systems including patents and clinical trials, highlighting their potential for improving the treatment of various ocular diseases. Furthermore, this review explores marketed ophthalmic emulsions and future prospects for integrating these NDDSs into clinical ophthalmology, emphasizing their ability to overcome ocular barriers and enhance therapeutic efficacy. Full article

The low aqueous solubility of many new drug candidates, a key challenge in oral drug development, has been effectively addressed by liquid self-emulsifying drug delivery systems (SEDDS). However, the inherent instability and manufacturing limitations of liquid formulations have prompted significant research into solid SEDDS. This review provides a comprehensive analysis of the recent advancements in solid SEDDS, focusing on the pivotal roles of solid carriers and solidification techniques. We examine a wide range of carrier materials, including mesoporous silica, polymers, mesoporous carbon, porous carbonate salts, and clay-based materials, highlighting how their physicochemical properties can be leveraged to control drug loading, release kinetics, and in vivo performance. We also detail the various solidification methods, such as spray drying, hot melt extrusion, adsorption, and 3D printing, and their impact on the final product’s quality and scalability. Furthermore, this review explores applications of solid SEDDS, including controlled release, mucoadhesive technology, and targeted drug delivery, as well as the key commercial challenges and future perspectives. By synthesizing these diverse aspects, this paper serves as a valuable resource for designing high-performance solid SEDDS with enhanced stability, bioavailability, and functional versatility. Full article

Background: Self-emulsifying drug delivery system (SEDDS) is widely used to improve the oral bioavailability of hydrophobic drugs. Emulsion droplet size was revealed to be a critical parameter that influences the thermodynamic stability, drug solubility, and drug absorption of the SEDDS. A high proportion of surfactant and/or co-surfactant was usually employed to reduce the particle size, which may lead the low drug loading and undesirable gastrointestinal toxicity. Methods: This manuscript proposed a novel strategy to reduce the particle size of emulsions using the hybrid of medium and long-chain triglyceride (MCT and LCT) SEDDS without promoting the concentration of surfactants and co-surfactants. The composition of SEDDS was selected based on the drug solubility. Particle size distribution and zeta potential of emulsion particles were determined using the dynamic light scattering technique. The bioavailability of formulations was evaluated in a mouse model. Results: The particle size of the emulsion was reduced from 113.50 ± 0.34 nm (MCT SEDDS) and 371.60 ± 6.90 nm (LCT SEDDS) to 21.23 ± 0.30 nm (MCT&LCT SEDDS). Progesterone, a poorly water-soluble drug, was selected as the model drug in the investigation of SEDDS. The hybrid of MCT&LCT progesterone SEDDS exhibited reduced particle size, enlarged self-emulsifying ranges, and increased drug content in the aqueous phase after lipolysis compared with the conventional mono-MCT or LCT SEDDS. In addition, the bioavailability of progesterone in the MCT&LCT SEDDS formulation was 3.82-fold higher than that of Utrogestan^® (a clinical oral administrated product) in a mouse model. Full article

Background/Objectives: Previous studies have shown that unformulated extracts of Passiflora ligularis leaves exhibit promising antidiabetic activity. This research aimed to demonstrate that formulating the extract into a self-emulsifying drug delivery system (PLE-SEDDS) enhanced its antidiabetic activity in a high-fat-diet/streptozotocin-induced diabetic mouse model. Methods: Blood glucose levels (BGLs) of diabetic mice were monitored during 21 days of oral administration of P. ligularis extract (PLE) and PLE-SEDDS. Control groups included metformin (positive control), vehicle, and SEDDS vehicle (negative controls). The animals underwent an oral glucose tolerance test (OGTT). The oxidative stress markers superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation quantified by malondialdehyde (MDA) levels were measured in the kidney, liver, and pancreas, complemented with histopathological analysis. Additionally, plasma lipid profile parameters were evaluated. Results: The PLE-SEDDS formulation demonstrated superior efficacy compared to the PLE extract in improving antidiabetic outcomes. Animals treated with PLE-SEDDS exhibited a minimal increase in blood glucose levels (11.5%) during the OGTT, compared to 27.4% with PLE and over 77% in the vehicle groups. PLE-SEDDS also showed greater enhancement of SOD and CAT activity, along with a more pronounced reduction in MDA levels, indicating stronger protection against oxidative stress. Histological analysis revealed significant preservation of pancreatic islets, and lipid profile analysis showed greater reductions in triglycerides, cholesterol, and LDL-C, alongside increased HDL-C levels. Conclusions: Altogether, these findings suggest that PLE-SEDDS exhibits superior antihyperglycemic, hypolipidemic, and antioxidant effects compared to the unformulated extract, making this novel formulation a promising option for treating type 2 diabetes mellitus. Full article

Tropical forests are essential ecosystems recognized for their carbon sequestration and biodiversity benefits. As the world undergoes a simultaneous data revolution and climate crisis, accurate data on the world’s forests are increasingly important. Completely novel in approach, this study proposes a methodology encompassing two bespoke deep learning models: (1) a single encoder, double decoder (SEDD) model to generate a species segmentation map, regularized by a distance map in training, and (2) an XGBoost model that estimates the diameter at breast height (DBH) based on tree species and crown measurements. These models operate sequentially: RGB images from the ReforesTree dataset undergo preprocessing before species identification, followed by tree crown detection using a fine-tuned DeepForest model. Post-processing applies the XGBoost model and custom allometric equations alongside standard carbon accounting formulas to generate final sequestration estimates. Unlike previous approaches that treat individual tree identification as an isolated task, this study directly integrates species-level identification into carbon accounting. Moreover, unlike traditional carbon estimation methods that rely on regional estimations via satellite imagery, this study leverages high-resolution, drone-captured RGB imagery, offering improved accuracy without sacrificing accessibility for resource-constrained regions. The model correctly identifies 67% of trees in the dataset, with accuracy rising to 84% for the two most common species. In terms of carbon accounting, this study achieves a relative error of just 2% compared to ground-truth carbon sequestration potential across the test set. Full article

In the current context, the use of technologies in applications for multimodal dialogue systems with computers and emotion recognition through artificial intelligence continues to grow rapidly. Consequently, it is challenging for researchers to identify gaps, propose new models, and increase user satisfaction. The objective of this study is to explore and analyze potential applications based on artificial intelligence for multimodal dialogue systems incorporating emotion recognition. The methodology used in selecting papers is in accordance with PRISMA and identifies 13 scientific articles whose research proposals are generally focused on convolutional neural networks (CNNs), Long Short-Term Memory (LSTM), GRU, and BERT. The research results identify the proposed models as Mindlink-Eumpy, RHPRnet, Emo Fu-Sense, 3FACRNNN, H-MMER, TMID, DKMD, and MatCR. The datasets used are DEAP, MAHNOB-HCI, SEED-IV, SEDD-V, AMIGOS, and DREAMER. In addition, the metrics achieved by the models are presented. It is concluded that emotion recognition models such as Emo Fu-Sense, 3FACRNNN, and H-MMER obtain outstanding results, with their accuracy ranging from 92.62% to 98.19%, and multimodal dialogue models such as TMID and the scene-aware model with BLEU4 metrics obtain values of 51.59% and 29%, respectively. Full article

Self-emulsifying drug delivery systems (SEDDS) consist of isotropic mixtures of oils, surfactants, and solvents that after dispersion emulsify in the aqueous media of the gastrointestinal tract (GIT). SEDDS can deliver hydrophobic drugs, which could enhance their oral bioavailability by protecting them from precipitation and degradation. However, it is important to find the appropriate ratio of their excipients to produce emulsions with the desirable physicochemical characteristics. In this sense, Design of Experiments (DoE) approaches such as central composite design (CCD) and Box–Behnken design (BBD) can reduce the number of experiments necessary to determine the best composition and preparation process of a SEDDS formulation. Therefore, this article aims to discuss drug delivery through SEDDS and how DoE approaches can aid researchers in achieving product quality specifications and optimizing the formulation preparation processes. For this, the most recent and relevant papers were analyzed. This review is expected to guide future research directions for more rational development of SEDDS. Full article

Chagas disease, caused by Trypanosoma cruzi, remains a neglected tropical disease with limited and often suboptimal chemotherapeutic treatment options. The WHO recommends nifurtimox (NFX) for treating Chagas disease, which, although it is effective in the early stages of infection, has variable efficacy in the chronic phase and induces adverse effects that frequently compromise the continuity of the treatment. This study focused on the development and characterization of innovative lipid-based self-emulsifying drug delivery systems (SEDDSs) and poly(ε-caprolactone) implants containing NFX. The SEDDS formulations modified the NFX release extent and rate. The implant characterization included thermal analysis, X-ray diffraction, thermo-optical analysis, and scanning electron microscopy, confirming the low interaction between NFX and the polymer. In vitro assays demonstrated the enhanced anti-T. cruzi activity of the NFX-SEDDS, with minimal cytotoxicity in mammalian cells. In vivo studies using T. cruzi-infected mice revealed that both formulations effectively suppressed parasitemia, achieving cure rates comparable to those of the standard oral NFX treatment. Additionally, the implants showed improved tolerability and sustained efficacy, delivering a prolonged effect equivalent to 40 oral doses. These findings highlight the potential of these innovative NFX formulations as promising alternatives for treating Chagas disease, particularly in the chronic phase, offering improved adherence and comparable efficacy to the existing therapies. Full article

Self-emulsifying drug delivery systems (SEDDS) represent an innovative approach to improving the solubility and bioavailability of poorly water-soluble drugs, addressing significant challenges associated with oral drug delivery. This review highlights the advancements and applications of SEDDS, including their transition from liquid to solid forms, while addressing the formulation strategies, characterization techniques, and future prospects in pharmaceutical sciences. The review systematically analyzes existing studies on SEDDS, focusing on their classification into liquid and solid forms and their preparation methods, including spray drying, hot-melt extrusion, and adsorption onto carriers. Characterization techniques such as droplet size analysis, dissolution studies, and solid-state evaluations are detailed. Additionally, emerging trends, including 3D printing, hybrid systems, and supersaturable SEDDS (Su-SEDDS), are explored. Liquid SEDDS (L-SEDDS) enhance drug solubility and absorption by forming emulsions upon contact with gastrointestinal fluids. However, they suffer from stability and leakage issues. Transitioning to solid SEDDS (S-SEDDS) has resolved these limitations, offering enhanced stability, scalability, and patient compliance. Innovations such as personalized 3D-printed SEDDS, biologics delivery, and targeted systems demonstrate their potential for diverse therapeutic applications. Computational modeling and in silico approaches further accelerate formulation optimization. SEDDS have revolutionized drug delivery by improving bioavailability and enabling precise, patient-centric therapies. While challenges such as scalability and excipient toxicity persist, emerging technologies and multidisciplinary collaborations are paving the way for next-generation SEDDS. Their adaptability and potential for personalized medicine solidify their role as a cornerstone in modern pharmaceutical development. Full article

Background: Voriconazole is an antifungal drug, which is classified under Bio-Classification System-II and has low water solubility (0.71 mg/mL) and high permeability. Hardly any endeavors have been made to increase the bioavailability of voriconazole. Objective: To develop and evaluate a solid SMEDDS (self-microemulsifying drug delivery system) for antifungal activity. Methods: Based on solubility studies of Labrafil-M 1994 CS (oil), Cremophor-RH 40 (a surfactant) and Transcutol-HP (a co-surfactant) were selected as components of the SMEDDS and a pseudo-ternary phase diagram was prepared. Thereafter, the oil, surfactant, and co-surfactant were mixed with altered weight ratios (1:1/1:2/2:1) and evaluated through various in vitro, in vivo analyses. Results: The particle size of the optimized formulation was observed to be 19.04 nm and the polydispersity index (PDI) value was found to be 0.162 with steady-state zeta potential. The optimized liquid SMEDDS was converted into a solid SMEDDS. Various adsorbents, such as Aerosil-200, Avicel-PH101, Neusilin-US2, and Neusilin UFL2 were screened to better detect the oil-absorbing capacity and flow properties of the powder. Neusilin UFL2 was selected as an adsorbent due to its better oil-absorbing capacity. DSC, X-ray diffraction, and dissolution studies were carried out to characterize the formulation. Further, the Pharmacokinetic profile was also studied in Wistar rats and the Cmax, tmax, and AUC0→t were calculated. The Cmax and AUC0→t plasma concentration is considerably better for the SMEDDS than for the pure drug and marketed formulation. Conclusions: This investigation clearly reveals the potential of developing a solid SMEDDS for candidiasis and invasive aspergillosis treatment, with better efficacy as compared to the commercially available marketed formulation. Full article

Background/Objectives: This study compared two pilot scale continuous manufacturing methods of solid self-emulsifying drug delivery systems (SEDDSs) via hot melt extrusion (HME). Methods: A model poorly water-soluble drug carvedilol in low dose (0.5–1.0% w/w) was processed in HME either in a conventional powder form or pre-dissolved in the liquid SEDDS. Results: HME yielded a processable final product with up to 20% w/w SEDDS. Addition of carvedilol powder resulted in a non-homogeneous drug distribution in the extrudates, whereas a homogeneous drug distribution was observed in pre-dissolved carvedilol. SEDDSs were shown to have a plasticizing effect, reducing the HME process torque up to 50%. Compatibility between excipients and carvedilol in the studied ratios after HME was confirmed via DSC and WAXS, demonstrating their amorphous form. Solid SEDDSs with Kollidon^® VA64 self-emulsified in aqueous medium within 15 min with mean droplet sizes 150–200 nm and were independent of the medium temperature, whereas reconstitution of Soluplus^® took over 60 min and mean droplet size increased 2-fold from 70 nm to 150 nm after temperature increased from 25 °C to 37 °C, indicating emulsion phase inversion at cloud point. Conclusions: In conclusion, using Kollidon^® VA64 and pre-dissolved carvedilol in SEDDS has shown to yield a stabile HME process with a homogenous carvedilol content in the extrudate. Full article