Applicability of Raman and near-infrared spectroscopy in the monitoring of freeze-drying injectable ibuprofen.

The freeze-drying process is an expensive, time-consuming and rather complex process. Therefore, process analytical technology (PAT) tools have been introduced to develop an optimized process and control critical process parameters, which affect the final product quality. The aim of the present work was to study the applicability of at-line near-infrared (NIR) and Raman spectroscopy approach in the monitoring of the freeze-drying process. Freeze-dried powders, which were developed previously, were manufactured as a multi-component system, containing ibuprofen (IBP). The NIR proved to be a useful tool for the monitoring of the freeze-drying process, since it was able to determine residual moisture content (RMC) and hence predict its values by using the partial least square (PLS) model. In addition, the evaluation of the correlation between the NIR and off-line HPLC IBP content results showed that NIR spectra were consistent with the HPLC measurements, even though overlapping absorption bands in multi-component system were observed. This research also studied the ability of using the at-line Raman measurements for the evaluation of the crystallinity and polymorphic transformations during the process, such as IBP ionization and mannitol polymorphism. The results were in correlation with XRPD results, but parameters of PLS models were not optimal. Nevertheless, this approach still assured better process understanding. To conclude, high applicability of the at-line NIR in the monitoring of the freeze-dried powder production was successfully demonstrated, suggesting that it can be used as a single tool to monitor RMC and IBP content as well as process deviations during the freeze-drying process.

Development of a solid self-microemulsifying drug delivery system (SMEDDS) for solubility enhancement of naproxen.

CONTEXT: Comparative evaluation of liquid and solid self-microemulsifying drug delivery systems (SMEDDS) as promising approaches for solubility enhancement. OBJECTIVE: The aim of this work was to develop, characterize, and evaluate a solid SMEDDS prepared via spray-drying of a liquid SMEDDS based on Gelucire® 44/14 to improve the solubility and dissolution rate of naproxen. MATERIAL AND METHODS: Various oils and co-surfactants in combination with Gelucire® 44/14 were evaluated during excipient selection study, solubility testing, and construction of (pseudo)ternary diagrams. The selected system was further evaluated for naproxen solubility, self-microemulsification ability, and in vitro dissolution of naproxen. In addition, its transformation into a solid SMEDDS by spray-drying using maltodextrin as a solid carrier was performed. Scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) were used to evaluate the physical characteristics of the solid SMEDDS obtained. RESULTS: The selected formulation of SMEDDS was comprised of Miglyol 812®, Peceol™, Gelucire® 44/14, and Solutol® HS 15. The liquid and solid SMEDDS formed a microemulsion after dilution with comparable average droplet size and exhibited uniform droplet size distribution. In the solid SMEDDS, liquid SMEDDS was adsorbed onto the surface of maltodextrin and formed smooth granular particles with the encapsulated drug predominantly in a dissolved state and partially in an amorphous state. Overall, incorporation of naproxen in SMEDDS, either liquid or solid, resulted in improved solubility and dissolution rate compared to pure naproxen. CONCLUSION: This study indicates that a liquid and solid SMEDDS is a strategy for solubility enhancement in the future development of orally delivered dosage forms.

Mixed lipid phase SMEDDS as an innovative approach to enhance resveratrol solubility.

CONTEXT: Despite its promising therapeutic activities, clinical use of resveratrol (RSV) is compromised with unfavorable biopharmaceutical properties, namely low water solubility. OBJECTIVE: This work deals with improving RSV solubility and release rate through its incorporation in innovative mixed lipid phase self-microemulsifying drug delivery systems (SMEDDS). METHODS: (Pseudo)ternary diagrams were constructed for different oils and surfactant mixtures. Selected systems were further evaluated for RSV solubility, self-emulsification ability, accelerated stability, dynamic viscosity, compatibility with hard gelatin capsules and in vitro dissolution of RSV. RESULTS: Lipid phase composed of diverse lipid species, castor oil (long-chained triglyceride) and Capmul MCM (mixture of medium chain mono and diglycerides) allowed formulation of mixed lipid SMEDDS with lower surfactants content (60% Cremophor EL/RH 40/RH 60). Mixed lipid phase SMEDDS showed best self-emulsifying ability with regard to self-emulsifying time as well as droplet size and monodispersity of microemulsions obtained upon SMEDDS dilution with aqueous phase. Overall, incorporation of RSV in SMEDDS resulted in improved solubility (over 23-fold) and dissolution rate compared to crystalline RSV. All SMEDDS formulations were adequately viscous for filling into hard gelatin capsules (>150 mPacs for empty SMEDDS; >400 mPacs for RSV-loaded SMEDDS) and no leaking was observed during three months of storage. CONCLUSION: The presented work indicates the promising potential of mixed lipid SMEDDS formulations for future development of SMEDDS with lower surfactant content and no added cosolvents for incorporation of RSV and other poorly soluble drugs.

Simulating the digestion of lipid-based drug delivery systems (LBDDS): overview of in vitro lipolysis models.

One of the greatest challenges in the pharmaceutical science is the improvement of oral bioavailability of poorly soluble drugs. Lately, one of the most attractive approaches has been formulation of lipid based drug delivery systems. However, the emerging popularity of these systems in the last decade has brought to light the need for efficient methods for their in vitro evaluation that would serve as their in vivo behaviour prediction tool. Because lipids are subject to lipid digestion and multiple absorption pathways in vivo, simple dissolution tests are not predictive enough when testing lipid based delivery systems. To assert these needs, the in vitro lipolysis model has been developed, utilizing pancreatic enzymes, bile and phospholipids in a temperature controlled chamber to simulate in vivo digestion. However, with very variable physiological conditions in gastrointestinal tract, this model has not been yet standardised and experiments vary among different laboratories. This review discusses in vivo events following oral application of lipid based delivery, in vitro lipolysis models to emulate them and their future perspectives.

Lipid-based systems with precipitation inhibitors as formulation approach to improve the drug bioavailability and/or lower its dose: a review.

Lipid-based systems, such as self-microemulsifying systems (SMEDDS) are attracting strong attention as a formulation approach to improve the bioavailability of poorly water-soluble drugs. By applying the "spring and parachute" strategy in designing supersaturable SMEDDS, it is possible to maintain the drug in the supersaturated state long enough to allow absorption of the complete dose, thus improving the drug's bio-availability. As such an approach allows the incorporation of larger amounts of the drug in equal or even lower volumes of SMEDDS, it also enables the production of smaller final dosage forms as well as decreased gastrointestinal irritation, being of particular importance when formulating dosage forms for children or the elderly. In this review, the technological approaches used to prolong the drug supersaturation are discussed regarding the type and concentration of polymers used in liquid and solid SMEDDS formulation. The addition of hypromellose derivatives, vinyl polymers, polyethylene glycol, polyoxyethylene, or polymetacrylate copolymers proved to be effective in inhibiting drug precipitation. Regarding the available literature, hypromellose has been the most commonly used polymeric precipitation inhibitor, added in a concentration of 5 % (m/m). However, the inhibiting ability is mainly governed not only by the physicochemical properties of the polymer but also by the API, therefore the choice of optimal precipitation inhibitor is recommended to be evaluated on an individual basis.

Lyophilised protein formulations as a patient-centric dosage form: A contribution toward sustainability paradigm.

At present, society has embraced the fact apropos population aging and climate changes, that demand, amongst others, innovative pharmaceutical technologies, emphasising the development of patient-specific delivery systems and thus the provision of efficient and sustainable drugs. Protein drugs for subcutaneous administration, by allowing less frequent application, represent one of the most important parts of the pharmaceutical field, but their development is inevitably faced with obstacles in providing protein stability and suitable formulation viscosity. To gain further knowledge and fill the gaps in the already constructed data platform for the development of monoclonal antibody formulations, we designed a study that examines small model proteins, i.e., bovine serum albumin. The main aim of the presented work is to evaluate the effect of protein concentrations on critical quality attributes of both, pre-lyophilised liquid formulations, and lyophilised products. Through the study, the hypothesis that increasing protein concentration leads to higher viscosity and higher reconstitution time without affecting the stability of the protein was confirmed. The most important finding is that sucrose plays a key role in the lyophilisation of investigated protein, nevertheless, it can be predicted that, to ensure the beneficial effect of mannitol, its amount has to prevail over the amount of sucrose.

Mucoadhesive film for oral delivery of vaccines for protection of the respiratory tract.

The delivery of vaccines plays a pivotal role in influencing the strength and longevity of the immune response and controlling reactogenicity. Mucosal immunization, as compared to parenteral vaccination, could offer greater protection against respiratory infections while being less invasive. While oral vaccination has been presumed less effective and believed to target mainly the gastrointestinal tract, trans-buccal delivery using mucoadhesive films (MAF) may allow targeted delivery to the mucosa. Here we present an effective strategy for mucosal delivery of several vaccine platforms incorporated in MAF, including DNA plasmids, viral vectors, and lipid nanoparticles incorporating mRNA (mRNA/LNP). The mRNA/LNP vaccine formulation targeting SARS-CoV-2 as a proof of concept remained stable within MAF consisting of slowly releasing water-soluble polymers and an impermeable backing layer, facilitating enhanced penetration into the oral mucosa. This formulation elicited antibody and cellular responses comparable to the intramuscular injection, but also induced the production of mucosal IgAs, highlighting its efficacy, particularly for use as a booster vaccine and the potential advantage for protection against respiratory infections. The MAF vaccine preparation demonstrates significant advantages, such as efficient delivery, stability, and simple noninvasive administration with the potential to alleviate vaccine hesitancy.

The design, synthesis, and antioxidant activity of amphiphilic oximes and amidoximes.

New amphiphilic benzamidoxime, benzoxime, and aliphatic oxime derivatives of glycolipid mimetics were synthesized. The total antioxidant capacity of these amphiphilic derivatives was evaluated using DPPH assay. The observed antioxidant activity was the highest for benzamidoxime derivatives and glycolipid mimetics with two oxime functionalities, followed by benzoxime derivatives, glycolipid mimetics with one oxime group, and dimers of oxime. Due to their amphiphilic structure, which was a guidance for compound design and synthesis, these novel amphiphilic compounds can be proposed as potential antioxidants for tackling oxidative processes in two-phase systems, either biological (cell membranes) or artificial (emulsions).

Water-soluble chitosan eases development of mucoadhesive buccal films and wafers for children.

Oromucosal films and wafers are user-friendly solid dosage forms offering easy and convenient administration, as well as rapid or controlled drug delivery. The aim of this study was to develop prednisolone containing child-friendly chitosan-based mucoadhesive films and wafers with a prolonged residence time on the buccal mucosa. Four different chitosan types (different molecular weights, degree of deacetylation (DDA), pattern of deacetylation) were studied for films prepared by solvent-cast-evaporation and wafers by freeze-drying. Mucoadhesive properties correlated with swelling abilities and were dependent on the chitosan type, the solvent, and the preparation method. Mucoadhesive forces were higher for formulations containing chitosan with higher DDA and for wafers compared to films. The drug release was relatively fast, especially for films (approx. 90 % in 15 minutes) and steadier for wafers (90 % in 45-120 minutes). Permeability was evaluated using artificial membranes and HT29-MTX cell-monolayers. The developed formulations exhibited good biocompatibility. Organoleptic properties can be improved by choosing a homogenously deacetylated chitosan type that provides a more neutral pH. Using hydroxypropyl-beta-cyclodextrin-complexation for taste masking of bitter drugs also reduced wafers' drug release rate. Mucoadhesive wafers are promising alternatives to films with a slower drug release rate and stronger mucoadhesion.

Nanofibers with genotyped Bacillus strains exhibiting antibacterial and immunomodulatory activity.

Biofilm-associated diseases such as periodontitis are widespread and challenging to treat which calls for new strategies for their effective management. Probiotics represent a promising approach for targeted treatment of dysbiosis in biofilm and modulation of host immune response. In this interdisciplinary study, nanofibers with two autochthonous Bacillus strains 27.3.Z and 25.2.M were developed. The strains were isolated from the oral microbiota of healthy individuals, and their genomes were sequenced and screened for genes associated with antimicrobial and immunomodulatory activities, virulence factors, and transferability of resistance to antibiotics. Spores of two Bacillus strains were incorporated individually or in combination into hydrophilic poly(ethylene oxide) (PEO) and composite PEO/alginate nanofibers. The nanofiber mats were characterised by a high loading of viable spores (> 7 log CFU/mg) and they maintained viability during electrospinning and 6 months of storage at room temperature. Spores were rapidly released from PEO nanofibers, while presence of alginate in the nanofibers prolonged their release. All formulations exhibited swelling, followed by transformation of the nanofiber mat into a hydrogel and polymer erosion mediating spore release kinetics. The investigated Bacillus strains released metabolites, which were not cytotoxic to peripheral blood mononuclear cells (PBMCs) in vitro. Moreover, their metabolites exhibited antibacterial activity against two periodontopathogens, an antiproliferative effect on PBMCs, and inhibition of PBMC expression of proinflammatory cytokines. In summary, the developed nanofiber-based delivery system represents a promising therapeutic approach to combat biofilm-associated disease on two fronts, namely via modulation of the local microbiota with probiotic bacteria and host immune response with their metabolites.

Study of Immediate Release Spherical Microparticles Containing Clarithromycin using a Hot-melt Fluid Bed Technique.

The aim of the study was to evaluate a hot-melt technique for preparation of immediate release spherical microparticles containing clarithromycin with acceptable characteristics and process yield. A modified fluid bed apparatus with rotor insert was used to prepare spherical microparticles in the size range of 125-355 µm. Poloxamer 188, PEG-32 glyceryl laurate (Gelucire 44/14) and a mixture of polyethylene glycol (PEG) 4000 with PEG 400 were used as meltable binders. Key process parameters were identified and optimized and their influence on process yield and microparticles characteristics was determined. Microparticles with poloxamer 188 and PEG exhibited relatively good mechanical properties. Process yield was around 70% and 60% in the case of PEG and poloxamer 188 respectively. Microparticles prepared with PEG-32 glyceryl laurate exhibited poor mechanical properties and process yield compared to other microparticles. The process was shown to be limited by the bed temperature, exhibiting the best process stability with poloxamer 188 followed by PEG and PEG-32 glyceryl laurate. Dissolution rate and equilibrium concentration of clarithromycin released from prepared microparticles was improved compared to similar particles prepared by wet granulation.

Investigation of design space for freeze-drying injectable ibuprofen using response surface methodology.

This study explores the use of a statistical model to build a design space for freeze-drying two formulations with ibuprofen. A 2 × 3 factorial experimental design was used to evaluate independent variables (filling volume and annealing time) and responses as residual moisture content, specific surface area and reconstitution time. A statistical model and response surface plots were generated to define the interactions among the selected variables. The models constructed for both formulations suggest that 1 mL of filled volume and no annealing should be used to achieve optimal residual moisture content, specific surface area and reconstitution time. The proposed models were validated with additional experiments, in which the responses observed were mainly in close agreement with the predicted ones. Additionally, the established models demonstrate the reliability of the evaluation procedure in predicting the selected responses.

Dual influence of colloidal silica on skin deposition of vitamins C and E simultaneously incorporated in topical microemulsions.

BACKGROUND: Colloidal silica is the thickener of interest for topical formulations and can therefore be used to optimize the viscosity of both hydrophilic and lipophilic microemulsions (MEs). To the best of our knowledge, no information is available about the effect of topically applied colloidal silica on skin penetration of drugs. So, our aim was to determine its influence on the effectiveness of ME in the simultaneous delivery of vitamins C and E to the skin. METHODS: Two different aspects of silica possible function were investigated. Its effects on formulation characteristics were studied by determination of partition coefficient of the vitamins, their solubility and release profile. The direct impact of silica on the skin was further evaluated by transepidermal water loss measurements, scanning electron microscopy (SEM), and cell toxicity determination (MTT assay). RESULTS: The addition of colloidal silica to ME was shown to increase significantly the vitamins' solubility and their partition to the phase in which they were less soluble. Its presence also increased the amount of both vitamins in epidermis, which was confirmed by release studies. Furthermore, we demonstrated that colloidal silica interacts with excised skin. It decreased transepidermal water loss, probably by retaining water in the stratum corneum because of its massive accumulation in the upper layers, as revealed by SEM. CONCLUSION: The results confirmed that addition of colloidal silica in ME simultaneously loaded with vitamins C and E enhanced vitamins' skin bioavailability by its dual influence on delivery characteristics of ME as well as on skin properties.

A new approach for increasing ascorbyl palmitate stability by addition of non-irritant co-antioxidant.

The aim of this work was to test innovative approach for enhancing ascorbyl palmitate stability in microemulsions for topical application by addition of newly synthesized co-antioxidant 4-(tridecyloxy)benzaldehyde oxime (TDBO) and to investigate its antioxidant activity and finally to evaluate cytotoxicity of TDBO-loaded microemulsions on keratinocyte cells. TDBO significantly increased ascorbyl palmitate stability in oil-dispersed-in-water (o/w) microemulsions, most presumably due to reduction of ascorbyl palmitate radical back to ascorbyl palmitate, since TDBO free-radical scavenging activity was confirmed. Cytotoxicity experiments demonstrated no significant change in cell viability or morphology in the presence of TDBO-loaded microemulsions regarding unloaded microemulsions, although greater cytotoxicity was observed with increased microemulsion concentrations. Therefore, the incorporation of TDBO as non-cytotoxic co-antioxidant in o/w microemulsions is a promising new strategy for enhancing ascorbyl palmitate stability that could be used to support antioxidant network in the skin.

Solidification of SMEDDS by fluid bed granulation and manufacturing of fast drug release tablets.

Solidification of self-microemulsifying drug delivery systems (SMEDDS) is a rising experimental field with important potential for pharmaceutical industry, however fluid-bed granulation with SMEDDS is yet an unexplored solidification technique. The aim of the study was to solidify carvedilol-loaded SMEDDS utilizing fluid bed granulation process and to investigate how the formulation variables (type of solid carrier, optimization of granulation dispersion) and fluid-bed granulation process variables can be optimized in order to achieve suitable agglomeration process, high drug loading and appropriate product characteristics. Obtained granulates exhibited complete drug release, comparable to liquid SMEDDS and superior to crystalline carvedilol, nevertheless compromise between large SMEDDS loading and appropriate flow properties of the granules has to be made. Representative granulates with highest drug loading were further compressed into tablets. It was shown that the optimal excipient selection of compression mixture and compression force can lead to fast carvedilol release even from the tablets. Selfmicroemulsifying properties were not impaired neither after the solidification process and nor after the compression of solid SMEDDS into tablets. This suggests that fluid-bed granulation with SMEDDS offers a perspective alternative for solidification of the SMEDDS, enabling preservation of self-microemulsifying properties, acceptable drug loading and complete drug release.

Preparation and evaluation of celecoxib-loaded microcapsules with self-microemulsifying core.

The purpose of this study was to prepare alginate microcapsules with a self-microemulsifying system (SMES) containing celecoxib in the core. An Inotech IE-50 R encapsulator equipped with a concentric nozzle was used to prepare the microcapsules. The encapsulated SMES was shown to increase celecoxib solubility over that of the pure drug more than 400-fold. Microcapsules prepared with a high SMES:celecoxib ratio exhibited distinct core vesicles containing liquid SMES. By modifying the SMES and including an additional chitosan coating, drug loading in the range from 12-40% could be achieved with the degree of encapsulation ranging from 60-82%. Alginate microcapsules loaded with SMES and celecoxib showed increased dissolution rate of celecoxib over that of alginate microcapsules loaded with celecoxib or of the celecoxib alone. Compared to the previous report, drug loading capacity was significantly improved, enabling the formulation of dosage forms which are of suitable size for peroral application.

Temperature-sensitive microemulsion gel: an effective topical delivery system for simultaneous delivery of vitamins C and E.

Microemulsions (ME)--nanostructured systems composed of water, oil, and surfactants--have frequently been used in attempts to increase cutaneous drug delivery. The primary objective addressed in this work has been the development of temperature-sensitive microemulsion gel (called gel-like ME), as an effective and safe delivery system suitable for simultaneous topical application of a hydrophilic vitamin C and a lipophilic vitamin E. By changing water content of liquid o/w ME (o/w ME), a gel-like ME with temperature-sensitive rheological properties was formed. The temperature-driven changes in its microstructure were confirmed by rotational rheometry, viscosity measurements, and droplet size determination. The release studies have shown that the vitamins' release at skin temperature from gel-like ME were comparable to those from o/w ME and were much faster and more complete than from o/w ME conventionally thickened with polymer (o/w ME carbomer). According to effectiveness in skin delivery of both vitamins, o/w ME was found the most appropriate, followed by gel-like ME and by o/w ME carbomer, indicating that no simple correlation between vitamins release and skin absorption could be found. The cytotoxicity studies revealed good cell viability after exposure to ME and confirmed all tested microemulsions as nonirritant.

Lamellar liquid crystals maintain keratinocytes' membrane fluidity: An AFM qualitative and quantitative study.

Despite extensive investigations of lamellar liquid crystals for dermal application, the effects of these systems at the cellular level are still not well elucidated. The key aim of this study was to determine the elasticity and morphological features of keratinocytes after exposure to a lamellar liquid crystal system (LLCS) using atomic force microscopy (AFM) as the method of choice. Prior to AFM assessment, a cell proliferation test and light plus fluorescence imaging were applied to determine the sub-toxic concentration of LLCS. According to the AFM results, slightly altered morphology was observed in the case of fixed keratinocytes, while an intact morphology was visualized on live cells. From the quantitative study, decreased Young's moduli were determined for fixed cells (i.e., 8.6 vs. 15.2 MPa and 1.3 vs. 2.9 MPa for ethanol or PFA-fixed LLCS-treated vs. control cells, respectively) and live cells (i.e., ranging from 0.6 to 2.8 for LLCS-treated vs. 1.1-4.5 MPa for untreated cells), clearly demonstrating increased cell elasticity. This is related to improved membrane fluidity as a consequence of interactions between the acyl chains of cell membrane phosphatidylcholine and those of LLCS. What seems to be of major importance is that the study confirms the potential clinical relevance of such systems in treatment of aged skin with characteristically more rigid epithelial cells.

Solubilization of ibuprofen for freeze dried parenteral dosage forms.

Ibuprofen, a weakly acidic non-steroidal anti-inflammatory drug having poor aqueous solubility, is a challenging drug for the development of pharmaceutical formulations, resulting in numerous research attempts focusing on improvement of its solubility and consequently bioavailability. Most studies have been done for solid dosage forms, with very little attention paid to parenterals. Hence, the main purpose of the present study was to enhance ibuprofen solubility as a result of formulation composition and the freeze drying process. Moreover, the purpose was to prepare a freeze dried dosage form with improved ibuprofen solubility that could, after simple reconstitution with water for injection, result in an isotonic parenteral solution. Solubility of ibuprofen was modified by various excipients suitable for parenteral application. Drug interactions with selected excipients in the final product/lyophilisate were studied by a combined use of XRPD, DSC, Raman and ss-NMR. Analyses of lyophilized samples showed solubility enhancement of ibuprofen and in situ formation of an ibuprofen salt with the alkaline excipients used.

Self-microemulsifying tablets prepared by direct compression for improved resveratrol delivery.

The purpose of this study was to develop self-microemulsifying (SME-) tablets to improve resveratrol solubility whilst delivering resveratrol in a preferred tablet dosage form. Resveratrol was dissolved in liquid self-microemulsifying drug delivery system (SMEDDS) (10% w/w) and solidified through adsorption on several different solid carriers. Two ranges of synthetic amorphous silica (Sylysia® 290, 350, 470, 580; Syloid® 244FP, AL-1FP) as well as granulated magnesium aluminometasilicate (Neusilin® US2) were screened for their SMEDDS adsorbent capacity. The most efficient carrier from every range was chosen for further SME-tablet development. To counteract the high ratio of liquid in SME-tablets, additional dry binders (microcrystalline cellulose, copovidone) were added to the tableting mixture, as well as superdisintegrant (croscarmellose sodium) and lubricant (magnesium stearate). Finally, approx. 600 mg tablets were directly pressed using 12 mm flat face punch, containing 41.75% SMEDDS. Overall, all tablets exhibited sufficient hardness (>50 N), although it was negatively affected by higher compression force. Tablets with Neusilin® US2 proved to have highest hardness, as granulated structure of Neusilin® US2 provided best compaction properties needed for successful direct compression of tablets. All prepared SME tablet formulations disintegrated in under 10 min and formed microemulsions (droplet size < 100 nm) upon dilution with water, with Neusilin® US2 tablets exhibiting the lowest droplet size (<30 nm). While conventional dissolution test indicated incomplete resveratrol release from solid carriers in both pH 1.2 and 6.8 media, no difference fatty acid amount titrated during fasted state in vitro lipolysis between liquid and solid SMEDDS was observed. Moreover, accelerated stability tests confirmed over 90% of trans-resveratrol remained in solid SMEDDS following 90 days at 40 °C, with no crystallization of resveratrol observed during that time. To sum up, through adsorption on solid carriers, in particular Neusilin® US2, SMEDDS was successfully transformed into a directly compressible mixture and tableted without the loss of its self-microemulsifying ability.