Self-microemulsifying Drug Delivery System Research Articles

Formulation and in vitro evaluation of liposomal and self-microemulsifying drug delivery systems for oral delivery of cannabidiol.

Oral formulations for cannabidiol: Improved absolute oral bioavailability of biodegradable cannabidiol self-emulsifying drug delivery systems.

Although preclinical studies consistently indicate that sulfasalazine (SAS) and disulfiram (DSF) are promising agents for the prevention and treatment of lung cancer, their clinical efficacy is limited. This discrepancy is attributed to the poor bioavailability of the drugs. Therefore, in the present study, we explored whether delivery of lower doses of SAS and DSF in nano self-emulsifying drug delivery systems (Nano-SEDDS) improves their potency and efficacy in suppressing malignant progression of lung tumors. Mice were treated with the tobacco smoke carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and once lung adenoma developed, high doses of free SAS (250 mg/kg) + DSF (100 mg/kg) or SEDDS formulations containing lower doses of SAS+DSF (40 mg/kg SAS + 8, 16 or 40 mg/kg DSF) were administered by oral gavage, every other day, for 10 weeks. Although the doses of SAS and DSF contained in SAS+DSF-SEDDS were about 6-fold and 3-15-fold lower, respectively, than the doses of the respective free drugs, SAS+DSF-SEDDS was more effective than free SAS+DSF in reducing the multiplicity of bigger lung tumors (≥ 1 mm). These effects were parallelled by significant reductions in the multiplicity of adenoma with progression and adenocarcinoma histopathological lesions. Also, lung tumors from mice treated with SAS+DSF-SEDDS exhibited an increase in the level of 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA), lipid peroxidation products. Overall, our results show that the Nano-SEDDS formulation of SAS+ DSF is a promising approach to enhance the potency and efficacy of the drugs for lung cancer chemo-interception and treatment.

Licochalcone A (Lic A) is a natural chalcone compound extracted from Glycyrrhiza inflata Batal, which exhibits a broad spectrum of pharmacological activities, including anti-inflammatory, antioxidant, anti-tumor, analgesic, hepatoprotective and antibacterial properties. Regarding its pharmacological effects, Lic A demonstrates inhibitory effects on various tumors, such as hepatocellular carcinoma, colorectal carcinoma, and leukemia. These effects are achieved by modulating key signaling pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), mitogen- activated protein kinase (MAPK), and phosphatidylinositol 3-Kinase (PI3K)/Protein Kinase B (Akt). However, the therapeutic potential of Lic A is remarkably hampered by its poor aqueous solubility and low permeation efficiency, which lead to inadequate absorption and poor bioavailability, posing formidable challenges for both oral and transdermal delivery. To address these limitations, advanced technologies such as micelles, mesoporous silica nanoparticles, cell-penetrating peptides, self-microemulsifying drug delivery systems, and eutectogels have been employed to enhance the solubility, permeability, and bioavailability of Lic A, thereby expanding its potential applications. This review aims to summarize the pharmacological effects, signal pathways, and mechanisms of action of Lic A. Moreover, it discusses recent research progress in improving its oral and transdermal delivery efficiency, further summarizing its clinical application and development prospects. Collectively, the work provides a comprehensive reference and methodological guidance for in-depth investigations of Lic A, as well as the exploration and formulation optimization of other flavonoid ingredients.

Corneal fungal infections are a leading cause of blindness worldwide; however, poor ocular drug absorption limits current topical antifungal treatments. Itraconazole (ICZ), a potent antifungal agent, exhibits low aqueous solubility and limited permeability. This study aimed to develop self-emulsifying drug delivery systems (SEDDS) to enhance the solubility, permeability, and ocular cell uptake of ICZ, providing a more effective topical therapy. ICZ solubility was evaluated in various vehicles (Tween 80, Tween 60, Span 20, coconut oil, and olive oil). Ten optimized SEDDS formulations were prepared, with particle sizes ranging from 514 to 1,384nm (tenfold dilution). In vitro drug permeation was assessed using Franz diffusion cells with a parallel artificial membrane permeability assay. Cellular uptake was evaluated in ocular cell lines, and drug diffusion kinetics were analyzed using the Higuchi model. Formulation stability was assessed over a 6-month period. Formulation F1 achieved the highest permeation (96.71% ± 1.99%), followed by F3 (96.33% ± 3.24%) and F2 (80.98% ± 2.85%), whereas ICZ-PEG showed minimal permeation (11.55% ± 2.80%). The Higuchi model indicated diffusion-controlled transport. Cellular uptake was highest for F3, followed by F1 and F2, with approximately 50.3-, 38.6-, and 12.3-fold higher uptake than ICZ-PEG, respectively. All ICZ-SEDDS formulations remained stable for > 6months. ICZ-SEDDS markedly improved the solubility, permeability, and ocular cell uptake of ICZ compared with ICZ-PEG. The superior performance of formulation F3 highlights the potential of SEDDS as an effective strategy for overcoming limitations in topical antifungal therapy for corneal fungal infections.

Development, characterization and in vitro assessment of a novel self-microemulsifying drug delivery system to increase cannabidiol intestinal bioaccessibility.

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.

The increasing demand for plant-based therapies has highlighted the need for innovative delivery technologies to enhance the bioavailability of phytoconstituents. Ajwain (Carum copticum) is a medicinal plant recognized for its antioxidant, anti-inflammatory, and hepatoprotective attributes. Nevertheless, its therapeutic application is greatly affected by insufficient aqueous solubility and low absorption. Targeting the biopharmaceutical performance improvement of Ajwain seed extract (ASE) by integrating it into a self-microemulsifying drug delivery system (SMEDDS) was considered, along with assessing its protective effects. ASE underwent GC–MS analysis for phytochemical profiling, followed by solubility assessment in several oils, surfactants, and co-surfactants. The improved SMEDDS-ASE was characterized physicochemically for micelle formation potential, dispersibility, gastrointestinal stability, and polymer miscibility with ASE. The hepatorenal protective effects were evaluated in a rat model of acute hepatorenal injury generated by cisplatin (7.5 mg/kg, i.p.) through the assessment of serum biomarkers and histological analysis. SMEDDS-ASE exhibited the formation of tiny micelles with an average droplet size of 183 ± 5.8 nm in water, resulting in a dispersibility enhancement of at least 2.4 times compared to ASE in water. The treatment of SMEDDS-ASE (75 mg/kg and 150 mg/kg, p.o.) significantly reduces different serum biomarker levels (decreased ALT, AST, ALP; p < 0.01; reduced creatinine, BUN; p < 0.05), which is ascribed to improved hepatorenal protection in a dose-dependent manner compared to ASE. Histological examinations suggest that SMEDDS-ASE may initiate the protection of hepatic and renal cells against damage and inflammation, thereby offering benefits in preventing diseases associated with free radicals. These findings suggest that the prospective implementation of the SMEDDS-based method may effectively enhance ASE’s nutraceutical properties.

The oral bioavailability of drugs is often limited by metabolic barriers, including enzymatic degradation and active efflux processes in the gastrointestinal tract. Piperine, a pungent alkaloid found in black pepper (Piper nigrum), has garnered significant interest as a natural bioenhancer due to its multifaceted ability to inhibit cytochrome P450 enzymes, particularly CYP3A4, and efflux transporters such as P-glycoprotein (P-gp). These actions result in enhanced intestinal absorption and prolonged systemic retention of various therapeutic agents. Additionally, Piperine modulates intestinal permeability and alters the pharmacokinetics of drugs by interfering with first-pass metabolism. Recent developments in nanotechnology have led to innovative formulation strategies, such as nanoemulsions, liposomes, and self-emulsifying drug delivery systems, which further enhance Piperine's solubility, stability, and efficacy. However, despite its promising bioenhancing effects, Piperine exhibits limitations such as poor water solubility, dose-dependent toxicity, reproductive and hepatic concerns, and the potential for significant drug-drug interactions. This review critically examines the mechanistic pathways, formulation advances, pharmacological roles, safety issues, and clinical prospects of Piperine. Furthermore, it emphasizes the need for rigorous clinical trials and regulatory evaluation to validate Piperine's use in pharmaceutical applications. Overall, Piperine represents a potent, yet cautiously applicable, tool in modern drug delivery strategies.

Poor aqueous solubility remains one of the major challenges in the development of oral pharmaceutical formulations, as it significantly limits the bioavailability of many therapeutic agents. A large proportion of newly discovered drug candidates fall into Biopharmaceutics Classification System (BCS) Class II or IV, where solubility is a critical barrier to effective absorption. Enhancing the bioavailability of poorly soluble drugs is essential to achieve desired therapeutic outcomes, reduce dosing frequency, and improve patient compliance. Numerous formulation strategies have been developed to address this issue, ranging from conventional physical and chemical modifications to advanced nanotechnology-based systems. Physical approaches such as particle size reduction, solid dispersions, and lipid-based formulations aim to improve dissolution rates, while chemical techniques like salt formation and prodrug development enhance solubility through molecular modification. Novel drug delivery systems, including nanoparticles, nanosuspensions, liposomes, and self-emulsifying drug delivery systems (SEDDS), offer promising alternatives by improving both solubility and stability. Despite their advantages, these strategies face limitations related to scalability, stability, and regulatory acceptance. This review provides a comprehensive overview of the current and emerging techniques used to enhance the bioavailability of poorly soluble drugs, with a focus on their mechanisms, advantages, limitations, and potential for clinical translation.

Formulation Development and Evaluation of Self-Microemulsifying Drug Delivery System (SMEDDS) of Azelnidipine for Hypertension

Self-emulsifying and lyotropic nanocarriers enhance solubility and antiparasitic efficacy of artesunic acid against different strains of Schistosoma mansoni.

Decoding excipients in lipid-based self-emulsifying drug delivery systems: Insights into physicochemical properties and therapeutic outcomes.

In recent years, bioactive constituents from plants have been investigated as an alternative to synthetic approaches of therapeutics. Mangiferin (MGF) is a xanthone glycoside extracted from Mangifera indica and has shown numerous medicinal properties, such as antimicrobial, anti-diarrhoeal, antiviral, anti-inflammatory, antihypertensive, anti-tumours, and anti-diabetic effects. However, there are numerous challenges to its effective therapeutic usage, including its low water solubility, limited absorption, and poor bioavailability. Nano formulation approaches in recent years exhibited potential for the delivery of phytoconstituents with key benefits of high entrapment, sustained release, enhanced solubility, stability, improved pharmacokinetics, and site-specific drug delivery. Numerous techniques have been employed for the fabrication of MGF-loaded Nano formulations, and each technique has its advantages and limitations. The nanocarriers that have been employed to fabricate MGF nanoformulations for various therapeutic purposes include; polymeric nanoparticles, nanostructure, lipid carriers, polymeric micelles, Nano emulsions, microemulsion & self-microemulsifying drug delivery system, solid lipid nanoparticles, gold nanoparticles, carbon nanotubes, transfersomes, nanoliposomes, ethosomes & transethosomes, and glycethosomes. Different biopharmaceutical characteristics (size, shape, entrapment efficiency, zeta potential, in vitro drug release, ex vivo drug permeation,, and in vivo studies) of the mentioned MGF-loaded nanocarriers have been methodically discussed. Patent reports are also included to further strengthen the potential of MGF in the management of diseases.

Objectives: The current work aimed to formulate and optimize a self-emulsifying microemulsion drug delivery system (SEME) for acemetacin (ACM) to increase ACM’s aqueous solubility, improve oral bioavailability, and reduce gastrointestinal complications. Methods: Screening of components capable of enhancing ACM solubility was performed. Pseudo-ternary phase diagrams were performed to choose the optimal formulation ratio. The ACM-SEME formulation’s composition was optimized using D-optimal design. Oil, Smix, and water percentages were used as independent variables, while globule size, polydispersity index, ACM content, and in vitro ACM release after 90 min were used as dependent variables. Also, thermodynamic stability and transmittance percentage tests were studied. Zeta potential was assessed for the optimized ACM-SEME formulation, which was then subjected to spray drying. The dried ACM-SEME was characterized using field-emission scanning electron microscope, Fourier-transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry. The dried ACM-SEME formulation was filled into hard gelatin capsules and coated with Eudragit L100 to achieve pH-dependent release. Results: The antinociceptive activity of ACM-SEME was evaluated in vivo using Eddy’s hot plate test in rats, revealing a significant prolongation of the noxious time threshold compared to control groups. Ex vivo permeation studies across rat intestinal tissue confirmed the enhanced permeation potential of the ACM-SEME. Conclusions: It was concluded that the developed ACM-SEME system demonstrated improved physicochemical properties, enhanced release behavior, and superior therapeutic performance, highlighting its potential as a safer and more effective oral delivery platform for ACM.

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.

Peptide drug delivery: Permeation behaviour and intracellular fate of hydrophobic ion pairs in self-emulsifying drug delivery systems.

This study presents a novel analytical and formulation strategy to enhance the oral delivery and quality assessment of Nirmatrelvir, a poorly water-soluble antiviral agent. A self-emulsifying drug delivery system (SEDDS) was developed using Labrafac MC 60, ethanol, and Transcutol HP (55:25:20), resulting in a nanoemulsion with a droplet size of 145.23 ± 3.23 nm, low polydispersity index (0.189 ± 0.023), and high transmittance (98.97 ± 0.25%). The formulation exhibited rapid emulsification (< 90 s) and significantly improved permeability, achieving a fivefold increase (Papp: 4.20 × 10-6 cm/s) across Caco-2 cell monolayers compared to the tablet formulation. A stability-indicating reverse-phase HPLC method was developed using a mobile phase of 5 mM potassium dihydrogen phosphate buffer (pH 4.0) and acetonitrile (40:60, v/v), and validated per ICH Q2(R1) guidelines. The method showed excellent linearity (R2 = 0.9999), accuracy (98.6%-100.2%), precision (%RSD < 0.3%), and robustness. An optimized sample preparation protocol ensured efficient extraction of Nirmatrelvir from the SEDDS matrix with minimal interference. Forced degradation studies under ICH Q1A(R2) demonstrated that Nirmatrelvir remained stable under oxidative (98.44%), thermal (98.45%), and photolytic (98.50%) conditions. Maximum degradation was observed under alkaline stress (20.56% at 0.5 N NaOH), followed by acidic stress (13.53% at 5 N HCl). The major alkaline degradant (Rt 2.7 min) was characterized by LC-TQ/MS (m/z 518.2 [M+H]⁺). The method's sustainability was supported by an AGREE score of 0.64 and a Whiteness score of 85.4, offering a validated platform for routine analysis of Nirmatrelvir in lipid-based formulations.

Impact of droplet size and surface charge on oral bioavailability of Norcantharidin-loaded SEDDS: Mechanistic insights into lymphatic transport and intestinal permeability.

The oral route is a preferred method for drug administration; however, lipophilic drugs often suffer from poor water solubility, significantly limiting their therapeutic effectiveness. Traditional approaches like complexation, micronization, and solid dispersion have been explored, but each comes with inherent limitations. Self-Emulsifying Drug Delivery Systems (SEDDS) have emerged as a promising strategy to address solubility challenges. These systems incorporate drug molecules into a mixture of oils, surfactants, and cosolvents to enhance solubility. Ternary phase diagrams are frequently utilized to determine optimal component ratios for effective formulation. SEDDS maintain drugs in a solubilized form within gastrointestinal fluids and protect peptide drugs from enzymatic degradation-a common issue in conventional formulations. They also facilitate the formation of stable emulsions at the target site, enhancing drug absorption. Additionally, the ability of SEDDS to traverse the blood-brain barrier (BBB) increases their applicability in treating neurological disorders. The findings emphasize the utility of SEDDS in overcoming the solubility and stability challenges faced by poorly water-soluble drugs. Their capacity to enhance drug absorption and protect bioactive molecules from degradation aligns with current efforts to improve oral drug delivery systems. However, formulation complexities and variability in in vivo performance remain areas requiring further investigation. This review outlines the formulation strategies, characterization methods, and evaluation techniques for SEDDS, emphasizing their potential in enhancing the bioavailability of poorly soluble drugs, particularly those aimed at the central nervous system. SEDDS offer a promising platform for improving therapeutic outcomes across diverse clinical settings.