Emulsifying Drug Delivery System Research Articles

Optimization and Characterization of Self Nano Emulsifying Drug Delivery System (SNEDDS) Naringenin Components with D-Optimal Mixture Design Method and Anti-Aging Test In Vivo

Optimization and Characterization of Self Nano Emulsifying Drug Delivery System (SNEDDS) Naringenin Components with D-Optimal Mixture Design Method and Anti-Aging Test In Vivo

Solid Self Nano-Emulsifying Drug Delivery System of Dasatinib: Optimization, In-vitro, Ex-vivo and In-vivo assessment.

Aim: Dasatinib (DST) is an oral tyrosine kinase inhibitor with poor aqueous solubility. To outwit this issue, a solid self-nano emulsifying drug delivery system (S-SNEDDS) of DST was formulated.Methods: I-optimal mixture design was used for optimization of DST-loaded SNEDDS using Linalool, Cremophor RH40 and Transcutol P. S-SNEDDS underwent physicochemical characterization, in-vitro release and ex-vivo permeation, cell-based assays and pharmacokinetic study.Results: DST-S-SNEDDS showed globule size and PDI of 141.53±5.371nm and 0.282±0.020, respectively. DST-S-SNEDDS revealed significantly lower IC50 (1.825μg/mL) than free DST (7.298μg/mL) in MDA-MB-231. In-vivo pharmacokinetic study revealed 1.94-fold increment in AUC0-t for the DST-S-SNEDDS group than free DST.Conclusion: S-SNEDDS could be promising approach for improving bioavailability and efficacy of DST.

Enhanced Wound Healing Activity in Animal Model via Developing and Designing of Self-nano Emulsifying Drug Delivery System (SNEDDS) for the Co-delivery of Hesperidin and Rutin

Enhanced Wound Healing Activity in Animal Model via Developing and Designing of Self-nano Emulsifying Drug Delivery System (SNEDDS) for the Co-delivery of Hesperidin and Rutin

Quality by Design Optimization of Telmisartan-loaded Self-nanoemulsifying Drug Delivery Systems

Aim: This study aimed to develop a QbD-based SNEDDS for Telmisartan to enhance its biopharmaceutical performance. Background: Quality by Design (QbD) was incorporated by selecting the Critical Process Pa-rameters (CPPs) as influential variables upon the desired responses. Using Design of Experiments (DoE) software, oil, and S/CoS were tested for pre-isotropic compatibility and formulation im-provement. A heating-cooling cycle and phase separation were used to determine the formula-tions' dispersibility, self-emulsifying time, mean globule size, and stability. Objective: Using Design of Experiments (DoE) software, oil (Capmul MCM C-10) and surfactant (Labrasol)/co-surfactant (Tween-20, and PEG-600) (S/CoS) ratios were optimized for pre-isotropic compatibility and formulation improvement. Methods: Aerosil-200, Sylysia-350, 550, and 730 were used as porous carriers, and Neusilin US2 as an adsorbing agent resulted in free-flowing granules of self-nano emulsifying drug delivery systems. The SNEDDS was further formulated into tablets using a direct compression technique with enhanced disintegration properties. Results: The prepared SNEDDS tablets exhibited a 71% increase in drug dissolution as compared to the pure drug and marketed formulation after the in vitro dissolution studies. Conclusion: This QbD approach offers a promising strategy for developing SNEDDS formula-tions for poorly soluble drugs like Telmisartan.

Application of quality by design in optimization of nanoformulations: Principle, perspectives and practices.

Nanoparticulate drug delivery systems (NDDS) based nanoformulations have emerged as promising drug delivery systems. Various NDDS-based formulations have been reported such as polymeric nanoparticles (NPs), nanoliposomes, solid lipid NPs, nanocapsules, liposomes, self-nano emulsifying drug delivery systems, pro liposomes, nanospheres, microemulsion, nanoemulsion, gold NPs, silver NPs and nanostructured lipid carrier. They have shown numerous advantages such as enhanced bioavailability, aqueous solubility, permeability, controlled release profile, and blood-brain barrier (BBB) permeability. This advantage of NDDS can help to deliver pure drugs to the target site. However, the formulation of nanoparticles is a complex process that requires optimization to ensure product quality and efficacy. Quality by Design (QbD) is a systemic approach that has been implemented in the pharmaceutical industry to improve the quality and reliability of drug products. QbD involves the optimization of different parameters like zeta potential (ZP), particle size (PS), entrapment efficiency (EE), polydispersity index (PDI), and drug release using statistical experimental design. The present article discussed the detailed role of QbD in optimizing nanoformulations and their advantages, advancement, and applications from the industrial perspective. Various case studies of QbD in the optimization of nanoformulations are also discussed.

Enhancing Oral Bioavailability of Domperidone Maleate: Formulation, In vitro Permeability Evaluation In-caco-2 Cell Monolayers and In situ Rat Intestinal Permeability Studies.

The domperidone maleate, a lipophilic agent classified as a Biopharmaceutical Classification System Class II substance with weak water solubility. Self- Emulsifying Drug Delivery System is a novel approach to improve water solubility and, ultimately bioavailability of drugs. This study aimed to develop and characterize new domperidone-loaded self-emulsifying drug delivery systems as an alternative formulation and to evaluate the permeability of domperidone-loaded self-emulsifying drug delivery systems by using Caco-2 cells and via single-pass intestinal perfusion method. Three self-emulsifying drug delivery systems were prepared and characterized in terms of pH, viscosity, droplet size, zeta potential, polydispersity index, conductivity, etc. Each formulation underwent 10, 100, 200, and 500 times dilution in intestinal buffer pH 6.8 and stomach buffer pH 1.2, respectively. Female Sprague Dawley rats were employed for in situ single-pass intestinal perfusion investigations. Results of the study revealed that the ideal self-emulsifying drug delivery systems formulation showed narrow droplet size, ideal zeta potential, and no conductivity. Additionally, as compared to the control groups, the optimum formulation had better apparent permeability (12.74 ± 0.02×10-4) from Caco-2 cell monolayer permeability experiments. The study also revealed greater Peff values (2.122 ± 0.892×10-4 cm/s) for the optimal formulation from in situ intestinal perfusion analyses in comparison to control groups (Domperidone; 0.802 ± 0.418×10-4 cm/s). To conclude, prepared formulations can be a promising way of oral administration of Biopharmaceutical Classification System Class II drugs.

Optimization of Naringenin Self-Nano Emulsifying Drug Delivery System (SNEDDS) Formula with D-optimal Mixture Design Method

Optimization of Naringenin Self-Nano Emulsifying Drug Delivery System (SNEDDS) Formula with D-optimal Mixture Design Method

Novel thiolated pluronic anchored gastro-retentive SEDDS of azithromycin against peptic ulcer

Peptic ulcer disease is a substantial health issue worldwide, owing to excessive use of non-steroidal anti-inflammatory drugs (NSAIDs) and poor hygienic conditions. Numerous therapeutic approaches including antibiotics and PPIs are commonly used, but these therapies are rendered with multi-drug resistance, increased frequency of dosing, less retention time, deceased safety, efficacy, and non-patient compliance. Herein, azithromycin (AZM), an expansive-spectrum antibiotic with notable anti-ulcer efficiency was integrated into a thiolated pluronic self- emulsifying drug delivery system (SEDDS) to enhance its solubility, mucoadhesion, stability, gastro-retention, and targeted drug delivery. Pluronics are triblock copolymers with excellent biocompatibility and amphiphilic properties, widely used in drug delivery, disease diagnosis, and treatment, among other applications. In vitro and in vivo tests were performed to assess the drug-release kinetics, H-pylori clearance, and efficacy. The optimized formulation possessed a size of 357 nm, PDI ≤ 0.5 and a zeta potential of 30 mV. Drug release was 85 % in 72 h, following Korsmeyer-Peppas model. Thiolated SEDDS proved to be extremely potent in eradicating bacterial load (40-load) when compared to alternative formulations. Furthermore, the retention duration, biofilm elimination and nanoparticle uptake were maximized. This novel thiolated SEDDS composition is highly recommended as it holds promising potential to markedly enhance the therapeutic outcomes of AZM in peptic ulcer treatment and overcomes the restrictions of current methodologies. The study not only boosts scientific comprehension of more effective drug-delivery techniques but also recommends significant implications for the broader disciplines of gastroenterology and personalized medicine.

Self Nanoelmusifying Drug Delivery System of Rosuvastatin: Bioavailability Evaluation and In vitro - In vivo Correlation.

Rosuvastatin, most commonly used in the form of calcium salt, belongs to the statin groups of synthetic antihyperlipidemic agents. Rosuvastatin possesses high permeability, however, its aqueous solubility is poor, causing a slow dissolution rate in water. Consequently, this dissolution rate has a decisive role in the release and absorption of rosuvastatin in the gastrointestinal tube. The aims of this study were to evaluate the absorption of the drug from the self-nano emulsifying drug delivery system of rosuvastatin (Ros SNEDDS) compared to rosuvastatin substance and to develop a level-A in vitro-in vivo correlation (IVIVC) for Ros SNEDDS. An in-house developed LC-MS/MS method was used to determine the concentrations of rosuvastatin in dog plasma. Six beagle dogs received an intravenous dose, Ros SNEDDS, rosuvastatin substance. In vitro dissolution of the Ros SNEDDS was carried out with different conditions. Correlation models were developed from the dissolution and absorption results of Ros SNEDDS. The results showed a 1.7-fold enhanced oral bioavailability and 2.1-time increase of rosuvastatin Cmax in Ros SNEDDS form, compared to the rosuvastatin substance. A 900 ml dissolution medium of pH of 6.6 has demonstrated its suitability, the in vitro dissolution model was studied and supported by the Weibull equation with a weighting factor of 1/y2 as it presented the lowest values of AIC. Ros SNEDDS demonstrated higher bioavailability of rosuvastatin in comparison to rosuvastatin substance and established a level A IVIVC used in future bioequivalence trials.

A Comprehensive Guide to the Development, Evaluation, and Future Prospects of Self-nanoemulsifying Drug Delivery Systems for Poorly Water-soluble Drugs.

Self-nano Emulsifying Drug Delivery Systems (SNEDDS) are novel formulations that can enhance the solubility and bioavailability of poorly water-soluble drugs. SNEDDS are composed of lipids, surfactants, co-solvents, and drugs and can spontaneously form nanoemulsions when mixed with water under mild agitation. SNEDDS can be formulated as liquid or solid dosage forms and can improve drug absorption by increasing the interfacial area, protecting the drug from degradation, and facilitating lymphatic transport. SNEDDS is characterized by various parameters such as particle size, zeta potential, droplet morphology, emulsification efficiency, drug solubility, and stability. SNEDDS offers several advantages over conventional dosage forms, such as dose reduction, faster onset of action, reduced variability, versatility, and ease of formulation. However, SNEDDS also face some limitations and challenges, such as drug precipitation, cost-effectiveness, compatibility with capsule shells, and lack of predictive in vitro models. SNEDDS has a promising future in the field of pharmaceuticals, especially for personalized medicine and targeted drug delivery.

Solid Self-Nanoemulsifying Drug Delivery Systems of Furosemide: In Vivo Proof of Concept for Enhanced Predictable Therapeutic Response.

Liquid self-nano emulsifying drug delivery systems (SNEDDS) of furosemide (FSM) have been explored as a potential solution for enhancing solubility and permeability but are associated with rapid emulsification, spontaneous drug release, and poor in vivo correlation. To overcome the shortcoming, this study aimed to develop liquid and solid self-emulsifying drug delivery systems for FSM, compare formulation dynamics, continue in vivo therapeutic efficacy, and investigate the advantages of solidification. For this purpose, liquid SNEDDS (L-SEDDS-FSM) were formed using oleic acid as an oil, chremophore EL, Tween 80, Tween 20 as a surfactant, and PEG 400 as a co-surfactant containing 53 mg/mL FSM. At the same time, solid SNEDDS (S-SEDDS-FSM) was developed by adsorbing liquid SNEDDS onto microcrystalline cellulose in a 1:1 ratio. Both formulations were evaluated for size, zeta potential, lipase degradation, and drug release. Moreover, in vivo diuretic studies regarding urine volume were carried out in mice to investigate the therapeutic responses of liquid and solid SNEDDS formulations. After dilution, L-SEDDS-FSM showed a mean droplet size of 115 ± 4.5 nm, while S-SEDDS-FSM depicted 116 ± 2.6 nm and zeta potentials of -5.4 ± 0.55 and -6.22 ± 1.2, respectively. S-SEDDS-FSM showed 1.8-fold reduced degradation by lipase enzymes in comparison to L-SEDDS-FSM. S-SEDDS-FSM demonstrated a sustained drug release pattern, releasing 63% of the drug over 180 min, in contrast to L-SEDDS-FSM, exhibiting 90% spontaneous drug release within 30 min. L-SEDDS-FSM exhibited a rapid upsurge in urine output (1550 ± 56 μL) compared to S-SEDDS-FSM, showing gradual urine output (969 ± 29 μL) till the 4th h of the study, providing sustained urine output yet a predictable therapeutic response. The solidification of SNEDDS effectively addresses challenges associated with spontaneous drug release and precipitation observed in liquid SNEDDS, highlighting the potential benefits of solid SNEDDS in improving the therapeutic response of furosemide.

Throat spray formulated with virucidal pharmaceutical excipients as an effective early prophylactic or treatment strategy against pharyngitis post-exposure to SARS-CoV-2

Our study aimed to develop a virucidal throat spray using bioactive compounds and excipients, focusing on the preparation of Curcumin (CUR) in a self-nano emulsifying drug delivery system (SNEDDS). Two molecular docking studies against SARS-CoV-2 targets guided the selection of proper oil, surfactant, co-surfactant, and natural bioactive that would maximize the antiviral activity of the throat spray. Two self-nanoemulsifying formulas that were diluted with different vehicles to prepare eight CUR-loaded SNESNS (self-nanoemulsifying self-nanosuspension) formulas. In vitro characterization studies and in vitro anti-SARS-CoV-2 effect revealed that the optimal formula, consisted of 20 % Anise oil, 70 % Tween 80, 10 % PEG 400, and 0.1 %w/w CUR, diluted with DEAE-Dx. Preclinical toxicity tests on male rats confirmed the safety of a mild throat spray dose (5 µg/mL CUR). In a rat model of acute pharyngitis induced by ammonia, post-treatment with the optimal formula of CUR loaded SNESNS for one week significantly reduced elevated proinflammatory markers (TNF-α, IL6, MCP1, and IL8). In conclusion, our CUR-loaded SNESNS formula, at 5 µg/mL concentration, shows promising effect as a prophylactic throat spray against SARS-CoV-2 and as a treatment for pharyngitis.

The potential of a self-nano emulsifying drug delivery system for ethanol extract of red betel vine as an antibacterial agent against Mycobacterium tuberculosis and Pseudomonas aeruginosa

The potential of a self-nano emulsifying drug delivery system for ethanol extract of red betel vine as an antibacterial agent against Mycobacterium tuberculosis and Pseudomonas aeruginosa

Solubility Enhancement of Palbociclib Supersaturable Self-Nano Emulsifying Drug Delivery System by Central Composite Design

Solubility Enhancement of Palbociclib Supersaturable Self-Nano Emulsifying Drug Delivery System by Central Composite Design

APPROACH TO OPTIMIZE THE SELF-MICROEMULSIFYING DRUG DELIVERY SYSTEM FOR AZILSARTAN MEDOXOMIL USING BOX BEHNKEN DESIGN AND DESIRABILITY FUNCTION

Objective: Develop and optimize a novel self-micro emulsifying drug delivery system (SMEDDS) for enhancing the water solubility of Azilsartan (AZL) by employing the Box-Behnken design and the desirability function. Methods: The formulation of AZL-SMEDDS consists of clove oil (oil component), Tween 20 (surfactant), propylene glycol (co-surfactant) as the independent variables and the active drug. Using a 3-level Design, the impact of independent variables on the formulation was examined. These variables' specified ranges are 20-40 mg, 50-80 mg, and 5-30 mg for X1, X2 and X3 respectively. Particle size (Y1), PDI (Y2), and dissolution % (Y3) were the response variables investigated in this study. Results: The results indicated that the optimal values for Clove oil (X1), Tween 20 (X2), and Propylene glycol (X3) were determined to be 28.69, 76.45, and 24.93 (mg), respectively. Based on these optimized conditions, the predicted data points for the response variables Particle Size (Y1), Polydispersity (Y2), and dissolution % (Y3) were determined to be 59.85 nm, 0.729 and 55.406%, respectively. Conclusion: The empirical results obtained from the optimized formulation exhibited a strong correlation with the predicted values. The optimized AZL-SMEDDS formulation demonstrated a rapid rate of drug solubility and greater bioavailability than AZL powder.

Formulation and Characterization of Self-Microemulsifying Drug Delivery System (SMEDDS) of Sertraline Hydrochloride.

Sertraline hydrochloride is the most widely used selective serotonin reuptake inhibitor (SSRI) for the treatment of several depressive disorders. Its applicability is limited due to extensive metabolism and poor oral bioavailability of 44 %. The current research focused on improving the solubility and oral bioavailability of Sertraline by using microemulsions developed by a self-micro emulsifying drug delivery system (SMEDDS) for significant antidepressant action. SMEDDS were developed by selecting appropriate proportions of oil, surfactant, and co-solvents and out of them isopropyl myristate, tween 80 and propylene glycol were identified as best. The emulsification zone was demonstrated by a ternary phase diagram, and compatibility was confirmed with Fourier-transformed infrared spectroscopy (FT-IR). The formulated SMEDDS were characterized for robustness to dilution, globule size (GS), polydispersity index (PDI), viscosity, in-vitro dissolution and diffusion study, and drug release kinetics study. All the batches (A1-A9) passes the test and A3 was selected as an optimized batch that doesn't show phase separation, precipitation with globule size (101 nm), PDI (0.319), drug content (99.14±0.35 %), viscosity (10.71±0.02 mPa), self-emulsification time (46 sec), in-vitro drug release (98.25±0.22 %) within 8 h, release kinetics (Higuchi) and effective antidepressant in in-vitro diffusion studies. An optimized batch A3 observed circular in shape estimated by Transmission electron microscopy (TEM) and passes all the thermodynamic stability testing with loss of 0.271 mg of the drug after 90 days and showed marked antidepressant action with higher stability.

Evaluation of Stability and In vitro Anti-Cancer Activity of Dihydroquercetin Nanoemulsion

Background: Dihydroquercetin (DHQ), also known as taxifolin, is a flavonoid commonly found in many plants. Dihydroquercetin has been documented to have powerful antioxidant activity and many beneficial properties for human health, especially its ability to inhibit certain types of cancer cells. However, its low solubility and bioavailability are major obstacles to biomedical applications. Moreover, DHQ is chemically unstable and quickly degrades when exposed to alkaline conditions. background: Dihydroquercetin (DHQ), also known as taxifolin, is a flavonoid and commonly found in many plants. Dihydroquercetin has been documented to have powerful antioxidant activity and many beneficial properties for human health, especially its ability to inhibit certain types of cancer cells. However, its low solubility and bioavailability are major obstacles to biomedical applications. Moreover, DHQ is chemically unstable and quickly degrades when exposed to alkaline conditions. Objective: In the present study, a DHQ nanoemulsion formulation was prepared by Self Nano- Emulsifying Drug Delivery System (SNEDDS) technique to overcome the above disadvantages. Methods: The obtained nanoemulsion system was evaluated for its micro-properties, stability, and in vitro cytotoxic activity against some cancer cells using tetrazolium dyes (MTS assay). Results: Measurement results showed that the DHQ nanoemulsion was successfully synthesized with typical mean droplet sizes from 9 to 11 nm, and revealed excellent stability over time. Dihydroquercetin in nanoemulsion form is more stable than the non-encapsulated form, as evidenced by the maintenance of droplet size in the nanometer range when dispersed in aqueous solution for up to 48 hours. This stability is particularly pronounced in both acidic and neutral environments. In vitro experiments on cytotoxic activities against A549, Hela, and HepG2 cancer cell lines indicated that the prepared DHQ nanoemulsion effectively inhibited the growth of all these cell lines with IC50 values (μg/mL) of 8.0, 20.4, and 29.5 respectively. Conclusion: From the detailed results above, it is evident that the solubility and bioavailability of DHQ can be improved by creating its nanostructure in the form of nanoemulsions. Furthermore, the nano form of DHQ carried within stable nanoemulsions exhibited better performance in inhibiting cancer cells compared to free DHQ. Therefore, further research is required to explore the development of cancer therapeutics utilizing nano DHQ emulsions.

A Quality by Design Approach for Developing SNEDDS Loaded with Vemurafenib for Enhanced Oral Bioavailability.

Vemurafenib (VMF) is a practically insoluble (< 0.1μg/mL) and least bioavailable (1%) drug. To enhance its oral bioavailability and solubility, we formulated a reliable self-nano emulsifying drug delivery system (SNEDDS). A Quality by Design (QbD) approach was used to optimize the ratio of Capryol 90, Tween 80, and Transcutol HP. VMF-loaded SNEDDS was characterized for its size, polydispersity index (PDI), zeta potential, drug content, and transmittance. The in vitro release profile of the drug loaded in SNEDDS was compared to the free drug in two media, pH 6.8 and 1.2, and the data obtained were analyzed with different mathematical models. A reverse-phase ultra-pressure liquid chromatography (UPLC) technique with high sensitivity and selectivity was developed and validated for the quantification of VMF in analytical and bioanalytical samples. Dissolution efficiency for SNEDDS was estimated using different models, which proved that the developed novel SNEDDS formulation had a better in vitro dissolution profile than the free drug. A 2.13-fold enhanced oral bioavailability of VMF-loaded SNEDDS compared to the free drug demonstrates the superiority of the developed formulation. This work thus presents an overview of VMF-loaded SNEDDS as a promising alternative to improve the oral bioavailability of the drug.

Enhancement of lcariin aphrodisiac effect by self nano emulsifying drug delivery system (SNEDDS) method &amp;lrm;

Enhancement of lcariin aphrodisiac effect by self nano emulsifying drug delivery system (SNEDDS) method &amp;lrm;

Formulation And Evaluation of Diclofenac Sodium-Loaded Self-Microemulsifying Gel for Enhanced Topical Drug Delivery

Objective: This study aimed to develop a topical gel formulation of diclofenac sodium (DFS) utilizing a self-micro emulsifying drug delivery system (SMEDDS) to enhance solubility, bioavailability, and patient compliance while minimizing systemic side effects associated with oral administration. Methods: DFS solubility was evaluated in various oils, surfactants, and co-surfactants. A pseudo-ternary phase diagram guided the selection of optimal SMEDDS components. The SMEDDS formulation, comprising cinnamon oil, Tween 20, and propylene glycol, was converted into a gel using Carbopol 940. Both the liquid SMEDDS and gel underwent extensive physicochemical characterization, including drug content, pH, viscosity, spreadability, and in vitro/ex vivo diffusion studies. Key Findings: Cinnamon oil, Tween 20, and propylene glycol exhibited the highest DFS solubility and emulsification efficiency. The optimized SMEDDS formulation showed robust stability, rapid self-emulsification, high drug loading, and favorable droplet size (112.8 nm) and zeta potential (-11.36 mV). The gel demonstrated consistent drug release (79.70% over 1440 minutes) and improved skin permeation (71.30% over 1440 minutes). Conclusions: The DFS-loaded SMEDDS gel formulation significantly enhances the solubility, dissolution, and topical bioavailability of DFS, providing a promising alternative for managing arthritic pain and inflammation with reduced systemic side effects.