Search Results (43)

Objective: This study aimed to develop an oral celastrol-loaded self-microemulsifying drug delivery system (Cel-SMEDDS) to enhance the therapeutic efficacy against rheumatoid arthritis and reduce toxicity. Methods: The optimal Cel-SMEDDS formulation, identified through solubility screening, excipient compatibility assays, and pseudo-ternary phase diagram analysis, was characterized by particle size, PDI, zeta potential, in vitro release, and stability. In vitro anti-inflammatory activity was evaluated in LPS-induced RAW264.7 macrophages, while in vivo anti-RA efficacy was assessed in CIA mice via paw swelling, clinical scoring, serum TNF-α, and joint histopathology. Preliminary safety was examined by hematological, serum biochemical, and histopathological analyses in mice. Results: The optimal Cel-SMEDDS formulation consisted of LABRAFIL M 1944 CS-Kolliphor RH40-CAPRYOL 90 (0.2:0.48:0.32, w/w/w) with a drug loading of 1.5% (w/w). It spontaneously formed uniform microemulsions with a mean particle size of 26.70 nm, PDI of 0.067, and zeta potential of −2.87 mV. In vitro, Cel-SMEDDS showed enhanced cytotoxicity against M1-type macrophages (IC₅₀ = 0.1753 μg/mL vs. 0.2684 μg/mL for free Cel), significantly suppressed pro-inflammatory TNF-α and IL-1β expression, and upregulated anti-inflammatory IL-10. In CIA mice, oral Cel-SMEDDS reduced paw swelling by 37.42% (vs. 22.79% for free Cel), markedly decreased serum and intra-articular TNF-α levels, and alleviated articular cartilage damage. Preliminary safety evaluation demonstrated no significant abnormalities in hematological parameters, liver/kidney function, or major organ histology. Conclusions: The optimized oral Cel-SMEDDS effectively inhibits the expression of pro-inflammatory cytokine TNF-α both in vitro and in vivo, exhibits superior anti-RA activity compared to free Cel, and possesses favorable safety. This formulation addresses the key limitations of celastrol and shows promising potential for clinical translation in RA treatment. Full article

Background: H007 is a novel selective AMP-activated protein kinase (AMPK) activator with demonstrated efficacy against hyperlipidemia; however, its oral bioavailability is limited by poor solubility and low intestinal permeability. This study aimed to develop a self-microemulsifying drug delivery system (SMEDDS) incorporating a H007–phospholipid complex (H007-PC) to improve both solubility and intestinal permeability. Methods: H007-PC-SME was prepared by integrating phospholipid complexes into an SMEDDS formulation. The formulation was optimized on the basis of emulsification efficiency, droplet size, and zeta potential, and was then evaluated for stability, in vitro drug release, and cellular uptake. Different H007 formulations were orally administered to golden hamsters to assess bioavailability, and a chylomicron flow blockade hamster model was used to evaluate lymphatic transport. Results: The optimized H007-PC-SME showed good stability, rapid self-emulsification, and improved drug solubility. Relative to ordinary H007 tablets, the relative bioavailability of H007-SME and H007-PC-SME was 376.65% and 464.62%, respectively, when calculated from M1 exposure, and 314.01% and 463.55%, respectively, when calculated from MP exposure. When evaluated in a cycloheximide model, H007-SME and H007-PC-SME increased the lymphatic transport fraction of M1 from approximately 0% to 22% and 54%, and that of MP from approximately 1% to 28% and 52% compared with ordinary H007 tablets. Conclusions: H007-PC-SME combines stable phospholipid complex formation with strong self-emulsification performance and effective drug dissolution. By overcoming the intrinsic limitations of the H007 active pharmaceutical ingredient and ordinary H007 tablets, this formulation improves membrane permeability and lymphatic transport, thereby enhancing oral bioavailability and therapeutic potential. The formulation shows good stability and acceptable in vitro biocompatibility under the tested conditions. The preparation process is straightforward, reproducible, and suitable for further pharmaceutical development. Full article

Atorvastatin (ATV), a widely used statin, exhibits both cholesterol-lowering and anti-inflammatory effects. Apigenin (API), a natural flavonoid, also demonstrates potent anti-inflammatory activity. This study aimed to develop and validate a novel stability-indicating reverse-phase HPLC method for the simultaneous quantification of ATV and API in standard solutions and dual ATV–API-loaded self-microemulsifying drug delivery system (SMEDDS). Quality by Design (QbD) approach was used to define the quality target product profile (QTPP), critical quality attributes (CQAs), and identify critical method parameters (CMPs) through risk assessment. A central composite design (CCD) evaluated the effects of organic phase ratio, buffer pH, and flow rate on chromatographic responses, including retention time, tailing factor, and resolution. Separation was achieved using an Agilent Eclipse XDB C-18 column (5 µm, 4.6 × 150 min) with a mobile phase of acetonitrile and 0.1 M ammonium acetate buffer (pH 7.0) in a 40:60 (v/v) ratio, UV detection at 266 nm, and a flow rate of 0.4 mL/ min. The method met ICH and USP (2021) validation criteria, showing excellent linearity (0.1–10 µg/mL), precision, accuracy, and specificity. No interference from SMEDDS excipients or degradation products during stability studies was observed. This validated method offers a reliable tool for formulation development and routine analysis of ATV and API combinations Full article

Arterial hypertension is a major contributor to cardiovascular disease, the leading cause of death globally. Previously, our research group has demonstrated that both organic extracts from Heliopsis longipes roots and affinin—its principal bioactive compound—induce vasodilation and exert antihypertensive effects in L-NAME-induced hypertensive rats. However, the poor water solubility of these extracts limits their oral administration and dosing. To address this limitation, a self-microemulsifying drug delivery system (HL-SMDS) was developed from an ethanolic extract of H. longipes root to enhance its aqueous solubility and oral bioavailability. This study evaluated the antihypertensive efficacy of HL-SMDS in spontaneously hypertensive and L-NAME-induced hypertensive rat models, as well as its effects on endothelial reactivity. HL-SMDS significantly reduced systolic blood pressure in both models, demonstrating greater efficacy than the crude extract, likely due to improved solubility and systemic bioavailability of the active constituents. Moreover, HL-SMDS enhanced endothelial function in aortas from L-NAME-treated rats. These findings support the potential of HL-SMDS as a lipid-based phytopharmaceutical formulation that improves the oral bioavailability and antihypertensive effect of the ethanolic extract of H. longipes root. HL-SMDS offers a promising strategy for the development of phytopharmaceutical drugs to treat hypertension. Full article

Objectives: A novel two-step flow-through in vitro lipolysis model was developed for the evaluation of drug release from a self-microemulsifying drug delivery system (SMEDDS). Methods: Firstly, the SMEDDS was dispersed in an acidic medium. Subsequently, the pH was increased, and a lipolytic reaction was immediately initiated, accompanied by medium flow onset. The latter enabled increase of the initial low pH of the medium, improving the physiological relevance of the method by simulating dosage form retainment in the stomach and transfer to the duodenum, which is very important for a weakly basic active pharmaceutical ingredient (API) incorporated in an SMEDDS. Results: Conversely to the traditional pH-stat in vitro lipolysis, the developed method is not established on titration, as the reaction vessel pH is regulated by a medium flow and buffer capacity. Individual parameters, such as pancreatin activity, buffer capacity, and medium shift, were researched using traditional pH-stat in vitro lipolysis prior to their implementation in the flow-through setup. Conclusions: The concentration of the solubilized model API, carvedilol, was increased as pancreatin activity decreased and as buffer capacity increased. The ratios between release profiles obtained under different conditions utilizing the pH-stat and novel two-step flow-through in vitro lipolysis were comparable; however, the differences were more pronounced in the flow-through method. Full article

The objective of this work was to investigate the use of nanocrystalline cellulose (NCC) as a drug-delivery excipient for buccal films. Gel-like dispersions were created by blending either gel or powder NCC (gNCC or pNCC) with natural polymers (alginate, pectin, or chitosan) in water, with glycerol serving as a plasticiser. Ibuprofen (IBU) as an active pharmaceutical ingredient (API) was dissolved in a self-microemulsifying drug delivery system (SMEDDS) to improve its solubility prior to its addition to gel-like dispersions. Dispersions were dried, and resulting films were cut to 3 cm × 1.5 cm size, appropriate for buccal delivery. Rheological measurements revealed that shorter, thinner, and less crystalline nanocellulose fibres are more favourable for stronger gel properties. While overall, weaker gel structure prior to film casting also resulted in shorter disintegration time, this was not the case for NCC–chitosan films; here, the low solubility of chitosan in neutral media proved to be the main obstacle. Nevertheless, the prolonged disintegration of NCC–chitosan films did not impact the dissolution of IBU, as these films exhibited the fastest dissolution rate, followed by NCC–pectin and NCC–alginate. Furthermore, NCC properties significantly influenced the dissolution behaviour of the chitosan formulations, with gNCC favouring faster IBU release due to weaker gel formation prior to film casting. 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

Background: The lack of local availability for drugs in the colon can be addressed by preparing a self-microemulsifying drug delivery system (SMEDDS) of curcumin (Cur) which is ultimately used for the treatment of inflammatory bowel disease (IBD). Methods: From preformulation studies, Lauroglycol FCC (oil), Tween 80 (surfactant), Transcutol HP (co-surfactant), and Avicel (solid carrier) were selected for the preparation of blank liquid and solid Cur-loaded SMEDDSs (S-Cur-SMEDDSs). Results: Z-average size (12.36 ± 0.04 nm), zeta potential (−14.7 ± 0.08 mV), and polydispersity index (PDI) (0.155 ± 0.036) showed a comparative droplet surface area and charge of both SMEDDSs. The physicochemical stability of Cur in S-Cur-SMEDDSs was confirmed via FTIR, DSC, TGA, and XRD analyses, while morphological analysis through SEM and atomic force microscopy (AFM) confirmed Cur loading into SMEDDSs with an increased surface roughness root mean square (RMS) of 11.433 ± 0.91 nm, greater than the blank SMEDDS. Acute toxicity studies with an organ weight ratio and % hemolysis of 15.65 ± 1.32% at a high concentration of 600 mM showed that S-Cur-SMEDDSs are safe at a medium dose (0.2–0.8 g/kg/day). The excellent in vitro antioxidant (68.54 ± 1.42%) and anti-inflammatory properties (56.47 ± 1.17%) of S-Cur-SMEDDS proved its therapeutic efficacy for IBD. Finally, S-Cur-SMEDDS significantly improved acetic acid-induced IBD in albino rats through a reduction in the disease activity index (DAI) and macroscopic ulcer score (MUS) from 4.15 ± 0.21 to 1.62 ± 0.12 at 15 mg/kg/day dose, as confirmed via histopathological assay. Conclusions: Based on the above findings, S-Cur-SMEDDS appears to be a stable, less toxic, and more efficacious alternative for Cur delivery with strong competence in treating IBD. Full article

Objectives: This study aims to create an innovative self-microemulsifying drug delivery system (SMEDDS) suppository for ibuprofen (IBU) using semisolid extrusion (SSE) three-dimensional (3D) printing technology. Methods: Based on solubility studies and the ability to form a transparent microemulsion upon dilution, a selected oil, surfactant, and co-surfactant were utilized to prepare SMEDDS-3DPS containing IBU. The optimal formulation consisted of 10% Triacetin, 80% Gelucire 48/16, and 10% Tetraethylene glycol. SSE 3D printing was employed to create three different-sized suppositories with varying drug contents. These suppositories were assessed for their physicochemical properties, content uniformity, and dissolution profiles. Results: The prepared mixture exhibited suitable physical properties for printing, with nano-sized emulsion droplets providing a large surface area for improved drug absorption in the rectum. Characterization techniques such as differential scanning calorimetry, powder X-ray diffraction, and Fourier transform infrared spectroscopy indicated that IBU was present in the formulation in an amorphous state. Additionally, in vitro dissolution tests demonstrated that SMEDDS-3DPS had a significantly higher initial dissolution rate compared with IBU powder. Conclusions: This research suggests that SMEDDS-3DPS, as a rectal IBU dosage form, can enhance the rectal bioavailability of IBU. It demonstrates the versatility of 3D printing as a novel manufacturing method for lipid-based suppositories and highlights the simplicity and adaptability of SSE 3D printing technology in producing customized suppositories tailored to individual patient needs, surpassing traditional methods. Full article

Objective: The aim of this study was to optimize the formulation of a C60-modified self-microemulsifying drug delivery system loaded with triptolide (C60-SMEDDS/TP) and evaluate the cytoprotective effect of the C60-SMEDDS/TP on normal human cells. Results: The C60-SMEDDS/TP exhibited rapid emulsification, an optimal particle size distribution of 50 ± 0.19 nm (PDI 0.211 ± 0.049), and a near-neutral zeta potential of −1.60 mV. The release kinetics of TP from the C60-SMEDDS/TP exhibited a sustained release profile and followed pseudo-first-order release kinetics. Cellular proliferation and apoptosis analysis indicated that the C60-SMEDDS/TP (with a mass ratio of TP: DSPE-PEG-C60 = 1:10) exhibited lower toxicity towards L02 and GES-1 cells. This was demonstrated by a higher IC50 (40.88 nM on L02 cells and 17.22 nM on GES-1 cells) compared to free TP (21.3 nM and 11.1 nM), and a lower apoptosis rate (20.8% on L02 cells and 26.3% on GES-1 cells, respectively) compared to free TP (50.5% and 47.0%) at a concentration of 50 nM. In comparison to the free TP group, L02 cells and GES-1 cells exposed to the C60-SMEDDS/TP exhibited a significant decrease in intracellular ROS and an increase in mitochondrial membrane potential (ΔψM). On the other hand, the C60-SMEDDS/TP demonstrated a similar inhibitory effect on BEL-7402 cells (IC50 = 28.9 nM) and HepG2 cells (IC50 = 107.6 nM), comparable to that of the free TP (27.2 nM and 90.4 nM). The C60-SMEDDS/TP group also exhibited a similar intracellular level of ROS and mitochondrial membrane potential compared to the SMEDDS/TP and free TP groups. Method: Fullerenol-Grafted Distearoyl Phosphatidylethanolamine-Polyethylene Glycol (DSPE-PEG-C60) was synthesized and applied in the self-microemulsifying drug delivery system. The C60-SMEDDS/TP was formulated using Cremophor EL, medium-chain triglycerides (MCT), PEG-400, and DSPE-PEG-C60, and loaded with triptolide (TP). The toxicity and bioactivity of the C60-SMEDDS/TP were assessed using normal human liver cell lines (L02 cells), normal human gastric mucosal epithelial cell lines (GES-1 cells), and liver cancer cell lines (BEL-7402 cells and HepG2 cells). The production of reactive oxygen species (ROS) after the C60-SMEDDS/TP treatment was assessed using 2′,7′-dichlorofluorescein diacetate (DCFDA) staining. The alterations in mitochondrial membrane potential (ΔψM) were assessed by measuring JC-1 fluorescence. Conclusions: The cytoprotection provided by the C60-SMEDDS/TP favored normal cells (L02 and GES-1) over tumor cells (BEL-7402 and HepG2 cells) in vitro. This suggests a promising approach for the safe and effective treatment of TP. Full article

Berberine hydrochloride (BH) is a versatile bioactive compound derived from the plants of the Berberis genus, known for its various pharmacological effects. However, its oral bioavailability is low due to its high hydrophilicity and limited permeability. To enhance its clinical efficacy and oral bioavailability, this study designed and prepared a BH-loaded self-microemulsifying drug delivery system (BH-SMEDDS), and characterized its in vitro and in vivo properties. Firstly, the optimal formulation of BH-SMEDDS was selected using solubility evaluations, pseudo-ternary phase diagrams, and particle size analysis. The formulation containing 55% Capmul MCM, 22.5% Kolliphor RH 40, and 22.5% 1,2-propanediol was developed. BH-SMEDDS exhibited stable physicochemical properties, with an average particle size of 47.2 ± 0.10 nm and a self-emulsification time of 26.02 ± 0.24 s. Moreover, in vitro dissolution studies showed significant improvements in BH release in simulated intestinal fluid, achieving 93.1 ± 2.3% release within 300 min. Meanwhile, BH-SMEDDS did not exhibit cytotoxic effects on the Caco-2 cells. Additionally, BH-SMEDDS achieved a 1.63-fold increase in oral bioavailability compared to commercial BH tablets. Therefore, SMEDDS presents a promising strategy for delivering BH with enhanced oral bioavailability, demonstrating significant potential for clinical application. Full article

The objectives of this study were to develop an optimized formulation for an Andrographis paniculata extract (AGPE)-loaded self-microemulsifying drug delivery system (SMEDDS) using an experimental design and evaluate the characteristics of the developed SMEDDS. The solubility of andrographolide (AGP) in various solvents was investigated. The pseudo-ternary phase was constructed to provide an optimal range for each component to form microemulsions (MEs). The formulation was optimized using an I-optimal design mixture type, where the physical stability, droplet size, polydispersity index, and zeta potential were examined. Soft capsules of the optimized AGPE-loaded SMEDDS were manufactured. The dissolution and ex vivo membrane permeation were studied. Oleic acid, Tween^® 80, and PEG 400 were the best solubilizers for AGP. The promising surfactant to co-surfactant ratio to generate ME was 3:1. The optimized SMEDDS contained 68.998% Tween^® 80, with 13.257% oleic acid and 17.745% PEG 400. The assayed content of AGP, uniformity of dosage unit, and stability complied with the expected specifications. The dissolution and membrane permeability of AGPE-loaded SMEDDS was significantly improved from the A. paniculata extract (p < 0.05). All in all, the developed optimized AGPE-loaded SMEDDS was proven to contain optimal composition and AGP content where a stable ME could spontaneously be formed with enhanced delivery efficacy. Full article

MT-102 is a new anti-inflammatory agent derived from Juglans mandshurica and Isatis indigotica. Its therapeutic potential is hindered by low aqueous solubility, impacting its in vivo efficacy. Therefore, this study aimed to develop a self-microemulsifying drug delivery system (SMEDDS) for MT-102 to enhance its oral efficacy in treating ulcerative colitis. Solubility assessment in different oils, surfactants, and cosurfactants led to a SMEDDS formulation of MT-102 using Capmul MCM, Tween 80, and propylene glycol. Based on a pseudoternary phase diagram, the optimal SMEDDS composition was selected, which consisted of 15% Capmul MCM, 42.5% Tween 80, and 42.5% propylene glycol. The resulting optimized SMEDDS (SMEDDS-F1) exhibited a narrow size distribution (177.5 ± 2.80 nm) and high indirubin content (275 ± 5.58 µg/g, a biomarker). Across an acidic to neutral pH range, SMEDDS-F1 showed rapid and extensive indirubin release, with dissolution rates approximately 15-fold higher than pure MT-102. Furthermore, oral administration of SMEDDS-F1 effectively mitigated inflammatory progression and symptoms in a mouse model of ulcerative colitis, whereas pure MT-102 was ineffective. SMEDDS-F1 minimized body weight loss (less than 5%) without any significant change in colon length and the morphology of colonic tissues, compared to those of the healthy control group. In addition, oral administration of SMEDDS-F1 significantly inhibited the secretion of pro-inflammatory cytokines such as IL-6 and TNF-α. In conclusion, the SMEDDS-F1 formulation employing Capmul MCM, Tween 80, and propylene glycol (15:42.5:42.5, w/w) enhances the solubility and therapeutic efficacy of MT-102. Full article

Poor aqueous solubility and dissolution limit the oral bioavailability of Biopharmaceutics Classification System (BCS) class II drugs. In this study, we aimed to improve the aqueous solubility and oral bioavailability of raloxifene hydrochloride (RLX), a BCS class II drug, using a self-microemulsifying drug delivery system (SMEDDS). Based on the solubilities of RLX, Capryol 90, Tween 80/Labrasol ALF, and polyethylene glycol 400 (PEG-400) were selected as the oil, surfactant mixture, and cosurfactant, respectively. Pseudo-ternary phase diagrams were constructed to determine the optimal composition (Capryol 90/Tween 80/Labrasol ALF/PEG-400 in 150/478.1/159.4/212.5 volume ratio) for RLX-SMEDDS with a small droplet size (147.1 nm) and stable microemulsification (PDI: 0.227). Differential scanning calorimetry and powder X-ray diffraction of lyophilized RLX-SMEDDS revealed the loss of crystallinity, suggesting a molecularly dissolved or amorphous state of RLX in the SMEDDS formulation. Moreover, RLX-SMEDDS exhibited significantly higher saturation solubility and dissolution rate in water, simulated gastric fluid (pH 1.2), and simulated intestinal fluid (pH 6.8) than RLX powder. Additionally, oral administration of RLX-SMEDDS to female rats resulted in 1.94- and 1.80-fold higher area under the curve and maximum plasma concentration, respectively, than the RLX dispersion. Collectively, our findings suggest SMEDDS is a promising oral formulation to enhance the therapeutic efficacy of RLX. Full article