Search Results (127)

Background: Caffeine (CAF), whether extracted from plants or synthesised as a chemical compound, is considered the safest among other xanthine alkaloids. Novel nano-cream formulations have been successfully developed and evaluated to increase the potential of caffeine as a skin cosmeceutical, targeting the minimisation of cellulite appearance. Methods: Nano-cream formulations were prepared through a process of hot-temperature emulsification, in a variety of homogeniser combinations. Results: When chemical penetration enhancers (CPEs) (lanolin, transcutol, and propylene glycol), either alone or in combination, were incorporated into the nano-cream formulations, the permeation of CAF through skin increased. All nano-cream formulations achieved sustained delivery of CAF into and through the skin over 8 h (IVPT). Quantification of CAF from skin tissues was achieved using high-performance liquid chromatography (HPLC). The nano-cream formulation containing lanolin (LAN) showed the highest CAF permeation (8.829 ± 1.472 µg/cm²/h) through the skin compared to CAF in an aqueous solution (2.533 ± 0.480 µg/cm²/h) and a commercial CAF cellulite product with the same CAF concentration (2.827 ± 0.555 µg/cm²/h). Therefore, 2% CAF nano-cream formulation containing LAN was chosen for clinical testing. A double-blind, randomised, placebo-controlled paired trial was conducted, in which each volunteer applied active and placebo creams to the upper thighs twice daily for 12 weeks. The effect of the cream on skin appearance was monitored over 12 weeks. The primary outcome measures were reduced cellulite scores from 3.96 (95% CI: 3.16–4.76) to 2.50 (95% CI: 1.70–3.30) (active) compared with placebo from 3.88 (95% CI: 3.08–4.67) to 2.83 (95% CI: 2.03–3.63). The effect sizes (E.S.) indicated a moderate effect for the active CAF nano-cream formulation (E.S. = 0.475), while the placebo (E.S. = 0.286) had a small effect. Conclusion: We concluded that our optimised 2% CAF nano-cream formulation containing LAN offered an effective formulation strategy for enhancing skin penetration in the IVPT study. The LAN nano-cream formulation demonstrated efficacy and tolerability, both objectively and subjectively, in a human clinical trial. 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

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

Background and Objectives: Age-related macular degeneration (AMD) is an age-associated retinal disorder characterized by blood–retinal barrier (BRB) breakdown and pathological angiogenesis, leading to vascular leakage. The intravitreal administration of anti-VEGF agents remains the most effective treatment for neovascular AMD. However, repetitive intravitreal injections have risks, causing side effects such as cataracts, bleeding, retina damage, and, in severe cases, post-injection endophthalmitis. Hence, the development of innovative drug delivery systems is essential to minimize the risks and discomfort associated with intravitreal injections. Materials and Methods: We developed a microemulsion (ME)-based topical drug delivery system incorporating α-linolenic acid (ALA). In brief, pseudo-ternary phase diagrams were constructed by the water titration method using different combinations of surfactants and cosurfactants (S_mix-Cremophor RH 40: Span 80: Transcutol P in ratios of 1:1.05, 1:1:1, 1:1:1.5) containing ALA as the oil phase. Three blank microemulsions (ME1, ME2, and ME3) were prepared and characterized based on the optimized pseudo-ternary phase equilibrium with a S_mix ratio of 1:1:1. Results: ME3, with an average particle size of 38.59 nm, was selected as the optimized formulation for developing drug-loaded ME containing Fenofibrate, Axitinib, and Sirolimus. The drug-loaded ME showed particle size (46.94–56.39 nm) and in vitro release displayed sustained and longer time drug release for 240 h. The irritation and antiangiogenic activities were evaluated using the hen’s egg chorioallantoic membrane (HET-CAM) assay employing the optimized ME loaded with each drug. Among the three drug-loaded ME, the Sirolimus ME showed a reduction in blood vessel sprouting in the HET-CAM assay, indicating strong antiangiogenic activity. Treatment with the optimized blank ME and Sirolimus ME significantly (p < 0.05) reduced COX-2 protein expression in LPS-stimulated RAW 264.7 cells, suggesting their potential anti-inflammatory effects. Conclusions: Overall, we suggest that the α-linolenic acid-based Sirolimus microemulsion may serve as a promising topical therapeutic approach for managing AMD and offering a potential alternative to invasive intravitreal injections. Full article

Background/Objectives: Breast cancer remains the most prevalent malignancy among women worldwide, with letrozole (LZ) serving as a critical aromatase inhibitor for hormone receptor–positive cases. However, long-term oral administration of LZ is often associated with systemic adverse effects and poor patient compliance. To overcome these limitations, new non-aqueous nanoemulgels (NEMGs) were developed for transdermal delivery of LZ. Methods: The NEMGs were formulated using glyceryl monooleate (GMO), Sepineo P600^®, Transcutol, propylene glycol, and penetration enhancers propylene glycol laurate (PGL), propylene glycol monocaprylate (PGMC), and Captex^®. Physicochemical characterization, solubility, stability, and in vitro permeation studies were conducted using Strat-M^® membranes, while in vivo pharmacokinetics were evaluated in rat models. Results: The optimized GMO/PGMC-based NEMG demonstrated significantly enhanced drug flux, higher permeability coefficients, and shorter lag times compared with other NEMGs and suspension emulgels. In vivo, transdermal application of the GMO/PGMC-based NEMG over an area of 2.55 cm² produced dual plasma absorption peaks, with 57% of the LZ dose absorbed relative to oral administration over 12 days. Shelf-life and accelerated stability assessments confirmed excellent physicochemical stability with negligible crystallization. Conclusions: The developed LZ NEMG formulations offer a stable, effective, and patient-friendly transdermal drug delivery platform for breast cancer therapy. This system demonstrates potential to improve patient compliance and reduce systemic toxicity compared to conventional oral administration. Full article

Background: This work aimed to enhance the solubility of Tadalafil (TDL), a BCS Class II drug, by preparing Type IV lipid-based formulations. Methods: Type IV formulations were prepared using surfactants and/or hydrophilic co-surfactants, resulting in oil-free systems. Results: Based on the solubility test, Transcutol^® HP exhibited the highest solubility for TDL (48.33 ± 0.004 mg/mL) and was selected as the co-surfactant. Among surfactants, Kolliphor^® PS80 (42.74 ± 2.29 mg/mL), Kolliphor^® EL (41.87 ± 2.50 mg/mL), Kollisolv^® PEG 400 (40.70 ± 0.30 mg/mL), and Kolliphor^® HS15 (31.40 ± 3.63 mg/mL) demonstrated high solubilization capacity. These were used to prepare formulations without the addition of an oil phase. The developed formulations resulted in a system with a nano-droplet size (<50 nm) and PDI values < 0.3, which was clear, transparent, and resistant to pH dilutions. The optimum Type IV lipid formulations were further characterized and demonstrated good thermodynamic stability under temperature and pH changes. The optimized formulation was adsorbed onto different carriers and transformed into solid TDL-loaded formulations. The in vitro dissolution rate of the drug from the solidified lipid formulations was studied in various dissolution media. It was observed that the solid formulations prepared with Neusilin US2^® (2:1) exhibited a significantly higher dissolution of over 95% within 5 min compared to the marketed product. The in vitro lipolysis studies demonstrated that F2 formulation maintained TDL in a supersaturated state throughout digestion, with limited enzymatic degradation of the excipients. Cytotoxicity evaluation using the MTT assay in Caco-2 cells confirmed the biocompatibility of both drug-free and TDL-loaded formulations, with IC₅₀ values of 19.55 µg/mL and 17.55 µg/mL, respectively. Conclusions: The overall results suggested that the developed solid Type IV lipid formulations can improve the dissolution rate of TDL, which would potentially lead to an improvement in its oral bioavailability and, consequently, a reduction in the treatment dose as a safe delivery system. Full article

Background: Centaurium erythraea Rafn. (C. erythraea) is a medicinal plant traditionally used in European folk medicine for the treatment of wounds, skin inflammations, and other dermatological conditions, in addition to its well-documented systemic antioxidant and anti-inflammatory effects. However, its topical applications remain insufficiently investigated, particularly using plant material collected from Romania. The purpose of this study was to prepare different ointment formulations containing C. erythraea Rafn. extract obtained from the aerial parts of the plant, using various excipients, and to evaluate their in vitro and in vivo efficacy. Methods: The phytochemical profile of C. erythraea extract was characterized using liquid chromatography–tandem mass spectrometry (LC–MS/MS). The lyophilized extract was pre-dissolved in different solubilizing agents—Transcutol^® P (diethylene glycol monoethyl ether), Capryol^® 90 (propylene glycol monocaprylate), or a combination of both—and then incorporated into five ointment formulations. Texture analysis and an in vitro membrane diffusion study were performed. The antioxidant capacity of the formulations was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, ferric reducing antioxidant power (FRAP), and total phenolic content (TPC) assays. Anti-inflammatory activity was evaluated in vitro using tumor necrosis factor-alpha (TNF-α)-induced interleukin-1 beta (IL-1β) production in human keratinocyte (HaCaT) cells, and in vivo using a carrageenan-induced rat paw edema model. Results: LC–MS/MS identified 18 polyphenolic compounds, with hyperoside (3.78 ± 0.05 µg/mL), protocatechuic acid (1.13 ± 0.06 µg/mL), chlorogenic acid (1.07 ± 0.06 µg/mL), and quercetin (0.53 ± 0.03 µg/mL) as the principal constituents. The formulation containing both Transcutol^® P and Capryol^® 90 exhibited the most pronounced antioxidant activity (65% DPPH inhibition; 69.71 ± 0.83 mg gallic acid equivalent/mL) and significantly reduced IL-1β levels by 45.7% compared to the inflamed control. In vivo, this formulation showed comparable anti-edematous effects to a methylprednisolone ointment. Furthermore, it demonstrated the highest skin permeation efficiency, with a quercetin diffusion coefficient of 35.12 × 10⁻⁵ cm²/min. Conclusions: These findings highlight the therapeutic potential of C. erythraea extract from aerial parts in topical formulations and underscore the enhancing role of Transcutol^® P and Capryol^® 90 in improving both the pharmacodynamic and pharmacokinetic properties of bioactive compounds. Full article

Background: Skin mycoses affect approximately 10% of the global population, and the range of effective topical antifungal agents remains limited. Voriconazole (VRC) is a broad-spectrum triazole with proven efficacy against drug-resistant fungal infections. This study aimed to develop and optimize VRC-loaded microemulsion (ME) polymer gels (Carbopol^®-based) for cutaneous delivery. Selected formulations also contained menthol (2%) as a penetration enhancer and potential synergistic antifungal agent. Methods: A comprehensive screening was performed using pseudoternary phase diagrams to identify stable oil/surfactant/co-surfactant/water systems. Selected MEs were prepared with triacetin, Etocas™ 35, and Transcutol^®, then gelled with Carbopol^®. Formulations were characterized for pH, droplet size, polydispersity index (PDI), and viscosity. In vitro VRC release was assessed using diffusion cells, while ex vivo permeation and skin deposition studies were conducted on full-thickness human skin. Rheological behavior (flow curves, yield stress) and texture (spreadability) were evaluated. Antifungal activity was tested against standard strain of Candida albicans and clinical isolates including a fluconazole-resistant strain. Results: The optimized ME (pH ≈ 5.2; droplet size ≈ 2.8 nm) was clear and stable with both VRC and menthol. Gelation produced non-Newtonian, shear-thinning hydrogels with low thixotropy, favorable for topical application. In ex vivo studies, performed with human skin, both VRC-loaded gels deposited the drug in the epidermis and dermis, with no detectable amounts in the receptor phase after 24 h, indicating retention within the skin. Menthol increased VRC deposition. Antifungal testing showed that VRC-containing gels produced large inhibition zones against C. albicans, including the resistant isolate. The VRC–menthol gel exhibited significantly greater inhibition zones than the VRC-only gel, confirming synergistic activity. Conclusions: ME-based hydrogels effectively delivered VRC into the skin. Menthol enhanced drug deposition and demonstrated synergistic antifungal activity with voriconazole. Full article

Background/Objectives: Raynaud’s phenomenon (RP) is characterized by an exaggerated vasoconstrictive response of small blood vessels in the fingers and toes to cold or stress. Oral therapy with tadalafil (TDL), a phosphodiesterase-5 inhibitor, is limited by systemic side effects and reduced patient compliance. This study aimed to develop and evaluate a TDL-loaded nanoemulgel for transdermal delivery as a non-invasive treatment alternative for cold-induced vasoconstriction. Methods: TDL-loaded nanoemulsions were prepared using the aqueous titration method with cinnamon oil as the oil phase and Cremophor RH40 and Transcutol as the surfactant–cosurfactant system. The optimized nanoemulsion was incorporated into a carbopol-based gel to form a nanoemulgel. The formulation was characterized for droplet size, morphology, thermodynamic stability, rheological properties, in vitro drug release, skin permeation, and pharmacokinetic behavior. Infrared thermography was employed to assess in vivo efficacy in cold-induced vasoconstriction models. Results: The optimized TDL nanoemulsion exhibited a spherical morphology, a nanoscale droplet size, and an enhanced transdermal flux. The resulting nanoemulgel displayed suitable physicochemical and rheological properties for topical application, a short lag time (0.7 h), and a high permeability coefficient (Kp = 3.59 × 10⁻² cm/h). Thermal imaging showed significant vasodilation comparable to standard 0.2% nitroglycerin ointment. Pharmacokinetic studies indicated improved transdermal absorption with a higher C_max (2.13 µg/mL), a prolonged half-life (t_1/2 = 16.12 h), and an increased AUC_0–24 compared to an oral nanosuspension (p < 0.001). Conclusions: The developed TDL nanoemulgel demonstrated effective transdermal delivery and significant potential as a patient-friendly therapeutic approach for Raynaud’s phenomenon, offering an alternative to conventional oral therapy. Full article

Background: Celastrol (Cela), a phytochemical extracted from Tripterygium wilfordii, has been extensively investigated for its potential anti-inflammatory, anti-psoriatic, antioxidant, neuroprotective, and antineoplastic properties. However, its clinical translation is limited due to poor bioavailability, low solubility, and nonspecific toxicity. This study aimed to develop and evaluate an inhalable Cela-loaded nanoemulsion (NE) formulation to enhance targeted drug delivery and therapeutic efficacy in non-small cell lung cancer (NSCLC). Methods: The NE formulation was optimized using Capmul MCM (25%), Tween 80 (20%), Transcutol HP (5%), and water (50%) as the oil, surfactant, co-surfactant, and aqueous phase, respectively. Physicochemical characterization included globule size, zeta potential, and drug release in simulated lung fluid. In vitro aerosolization performance, cytotoxicity in NSCLC cell lines (A549), scratch and clonogenic assays, and 3D tumor spheroid models were employed to assess therapeutic potential. Results: The NE showed a globule size of 201.4 ± 3.7 nm and a zeta potential of −15.7 ± 0.2 mV. Drug release was sustained, with 20.4 ± 5.5%, 29.1 ± 10%, 64.6 ± 4.1%, and 88.1 ± 5.2% released at 24, 48, 72, and 120 h, respectively. In vitro aerosolization studies indicated a median aerodynamic particle size of 4.8 ± 0.2 μm, confirming its respirability in the lung. Cell culture studies indicated higher toxicity of NE-Cela in NSCLC cells. NE-Cela significantly reduced A549 cell viability, showing a ~6-fold decrease in IC₅₀ (0.2 ± 0.1 μM) compared to Cela alone (1.2 ± 0.2 μM). Migration and clonogenic assays demonstrated reduced cell proliferation, and 3D spheroid models supported its therapeutic activity in tumor-like environments. Conclusions: The inhalable NE-Cela formulation improved Cela’s physicochemical limitations and demonstrated enhanced anti-cancer efficacy in NSCLC models. These findings support its potential as a targeted, well-tolerated therapeutic option for lung cancer treatment. Full article

The incorporation of essential oils into the oil phase of oil-in-water microemulsions is an emerging strategy for the development of stable water-based topical formulations. The introduction of a suitable polymer to formulate film-forming microemulsions may improve topical administration; however, the effect of formulation variables on film quality attributes has not been studied. In this study, thermodynamically stable microemulsion concentrates consisting of surfactant (Kolliphor^® RH40), alone or in combination with cosurfactant Transcutol^® at surfactant-to-cosurfactant mass ratio 7:3, cosolvent (propylene glycol), and synthetic oils (medium-chain triglycerides or isopropyl myristate) with tea tree, cinnamon, or thyme essential oil were formulated and diluted with hypromellose solution in a water/isopropanol mixture (1:1 w/w) to produce film-forming microemulsions. The type and concentration of synthetic and essential oils and cosurfactant influenced the dynamics of structural transformations upon dilution as well as the rheological behavior, viscosity, and pH of film-forming microemulsions. Films obtained by casting film-forming microemulsions were opalescent, smooth, flexible, and swellable in artificial sweat and water. The weight and yield of films increase with the synthetic oils present and without cosurfactant added. Optimizing the ratio of essential oil/synthetic oil, the type of synthetic oil, and the inclusion/exclusion of cosurfactant allows for achieving the targeted film attributes for cosmetic and pharmaceutical applications, including wound treatment. Full article

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

Background: Silibinin (SLB), a flavonoid derived from milk thistle, exhibits promising therapeutic properties but faces significant clinical limitations due to poor solubility and bioavailability. Objectives: This study focuses on the development and characterization of SLB-loaded nanoemulsions designed for mucosal delivery. Methods: Nanoemulsions were prepared using the spontaneous emulsification method, guided by pseudoternary phase diagrams to determine selected component ratios. Comprehensive characterization included particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency, rheological properties, and surface tension. Mucoadhesive properties were evaluated using quartz crystal microbalance with dissipation (QCM-D) to quantify interactions with mucin layers. Results: The combination of Capryol 90, Tween 80, and Transcutol in selected proportions yielded nanoemulsions with excellent stability and solubilization capacity, enhancing the solubility of silibinin by 625 times compared to its intrinsic solubility in water. The ternary phase diagram indicated that achieving nanoemulsions with particle sizes between 100 and 300 nm required higher concentrations of surfactants (60%), relative to oil (20%) and water (20%), with formulations predominantly composed of Smix (surfactant and cosurfactant mixture in a 1:1 ratio). Rheological analysis revealed Newtonian behavior, characterized by constant viscosity across varying shear rates and a linear torque response, ensuring ease of application and mechanical stability. QCM-D analysis confirmed strong mucoadhesive interactions, with significant frequency and dissipation shifts, indicative of prolonged retention and enhanced mucosal drug delivery. Furthermore, contact angle measurements showed a marked reduction in surface tension upon interaction with mucin, with the SLB-loaded nanoemulsion demonstrating superior wettability and strong mucoadhesive potential. Conclusions: These findings underscore the suitability of SLB-loaded nanoemulsions as a robust platform for effective mucosal drug delivery, addressing solubility and bioavailability challenges while enabling prolonged retention and controlled therapeutic release. Full article

Background/Objectives: The present study focused on the formulation and evaluation of novel topical systems containing Salvia officinalis (sage), emphasizing their antioxidant and anti-inflammatory properties. Sage, rich in carnosol, offers considerable therapeutic potential, yet its low water solubility limits its effectiveness in traditional formulations. The aim of our experimental work was to improve the solubility and thus bioavailability of the active ingredient by developing self-nano/microemulsifying drug delivery systems (SN/MEDDSs) with the help of Labrasol and Labrafil M as the nonionic surfactants, Transcutol HP as the co-surfactant, and isopropyl myristate as the oily phase. Methods: The formulations were characterized for droplet size, zeta potential, polydispersity index (PDI), encapsulation efficacy, and stability. The composition exhibiting the most favorable characteristics, with particle sizes falling within the nanoscale range, was incorporated into a cream and a gel, which were compared for their textural properties, carnosol penetration, biocompatibility and efficacy. Results: Release studies conducted using Franz diffusion cells demonstrated that the SNEDDS-based cream achieved up to 80% carnosol release, outperforming gels. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) test and enzyme-linked immunosorbent assays (ELISA) showed strong efficacy, with an in vivo carrageenan-induced rat paw edema model revealing that the SNEDDS-based cream significantly reduced inflammation. Conclusions: These findings highlight the potential of SNEDDS-enhanced topical formulations in improving therapeutic outcomes. Further research is warranted to confirm their long-term safety and efficacy. 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