Self-nanoemulsifying Drug Delivery System Formulation Research Articles

Formulation of self-nanoemulsifying drug delivery system (SNEDDS) of combined 70% ethanolic of Begonia medicinalis herbs and Moringa oleifera leaves

Background: Benalu batu (Begonia medicinalis) and kelor leaves (Moringa oleifera) are empirically used as alternative therapies by people in Central Sulawesi to maintain their health. Our previous research showed that the combination of these two plant extracts possessed an immunomodulatory activity. Self-Nanoemulsifying Drug Delivery System (SNEDDS) formulation was performed to improve the extract's bioavailability, solubility and stability. Objective: This study aims to formulate and characterise SNEDDS preparations of combined ethanolic extract of B. medicinalis herbs and M. oleifera leaves and further test its stability. Method: SNEDDS formulation was started by screening for proper oil, surfactant, and co-surfactant. The formula was then optimised using a ternary phase diagram and characterisation. The stability test was performed using centrifugation, heating-cooling, and freeze-thaw cycles. Results: The optimal SNEDDS formula consists of isopropyl myristate (10%), tween 80 (50%) and propylene glycol (40%). The characterisation values obtained were: Transmittance value 83.785 ± 0.275%, particle size 18.666 ± 0.208 nm, polydispersity index 0.664 ± 0.0085, and zeta potential -39.20 ± 0.2 mV. The formula was stable during three stability evaluation tests. Conclusion: The optimal formula met the SNEDDS characteristics requirements and showed good stability.

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.

Enhancing the Antiproliferative Activity of Perillyl Alcohol against Glioblastoma Cell Lines through Synergistic Formulation with Natural Oils.

Due to its volatility, photostability, and gastrointestinal toxicity, Perillyl Alcohol (POH), a monoterpenoid component of various plant species, is a chemotherapeutic drug with insufficient efficacy. Many naturally occurring bioactive compounds have well-known antiproliferative properties, including sefsol, jojoba, tea tree, and moringa oils. This study sought to develop an oil-based Self Nanoemulsifying Drug Delivery System (SNEDDS) using tween 80 as the surfactant and Dimethyl Sulfoxide (DMSO) or Polyethylene Glycol (PEG) 400 as the cosurfactant; the oils were used in a range of 10-20% to boost POH's anticancer efficacy. The formulations' size, charge, and impact on the viability of glioma cell lines, ANGM-CSS and A172, were evaluated. The developed SNEDDS formulations ranged from 3 nm to 362 nm in size, with electronegative surface charges between 5.05 and 17.0 mV and polydispersity indices between 0.3 and 1.0. The findings indicated that the antiproliferative effect of POH-loaded Nanoemulsion (NE) could be used as a possible anticancer therapy for glioblastoma in vitro, particularly when paired with the tested natural oils. Before asserting that this delivery technique is appropriate for glioblastoma therapy, additional in vitro and in vivo investigations are required.

Enhanced Stability and Improved Oral Absorption of Enzalutamide with Self-Nanoemulsifying Drug Delivery System.

The purpose of this study is to develop and evaluate a self-nanoemulsifying drug delivery system (SNEDDS) to improve the oral absorption of poorly water-soluble enzalutamide (ENZ). Considering the rapid recrystallization of the drug, based on solubility and crystallization tests in various oils, surfactants and co-surfactants, Labrafac PG 10%, Solutol HS15 80%, and Transcutol P 10%, which showed the most stable particle size and polydispersity index (PDI) without drug precipitation, were selected as the optimal SNEDDS formulation. The optimized SNEDDS formulation showed excellent dissolution profiles for all the drugs released at 10 min of dissolution due to the increased surface area with a small particle size of approximately 16 nm. Additionally, it was confirmed to be stable without significant differences in physical and chemical properties for 6 months under accelerated conditions (40 ± 2 °C, 75 ± 5% RH) and stressed conditions (60 ± 2 °C). Associated with the high dissolutions of ENZ, pharmacokinetic parameters were also greatly improved. Specifically, the AUC was 1.9 times higher and the Cmax was 1.8 times higher than those of commercial products (Xtandi® soft capsule), resulting in improved oral absorption. Taken together with the results mentioned above, the SNEDDS could be an effective tool as a formulation for ENZ and other similar drugs.

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.

Characteristic and Formulation Turmeric Extract Nanoemulsion as Alternative Moisturizer in Atopic Dermatitis

Currently, many moisturizers are developed with anti-inflammatory ingredients intended for mild and moderate atopic dermatitis (AD). One of the ingredients that can be developed is turmeric (Curcuma longa), which has potent anti-inflammatory activity. However, turmeric topical treatments require nano formulas due to their limited skin absorption. This study aims to obtain the optimal formulation of turmeric extract nanoemulsion as an alternative moisturizer for AD. The nanoemulsions are made by a self-nanoemulsifying drug delivery system (SNEDDS) using a simplex lattice design (SLD). Based on the solubility test, the oil components were sunflower oil, tween 80 as a surfactant, and polyethylene glycol (PEG) 400 as cosurfactant with a ratio of 1:8:1. The SNEDDS formulation was analyzed using software design expert version 10.03. The optimum SNEDDS formulation characteristic included an average droplet size of 13.37nm, an average polydispersity index (PDI) of 0.179, an average transmittance of 81.53%, and an average zeta potential of -38.57mV. Based on these results, it can be concluded that the turmeric extract formula meets the nanoemulsion criteria because the average droplet size is &lt;200nm, the droplet distribution is relatively homogeneous as illustrated by the small average PDI, the transmittancesare above 80%, and is relatively stable with a zeta potential &gt;±30mV.

FORMULATION AND OPTIMIZATION OF FUROSEMIDE SNEDDS: A COMPREHENSIVE STUDY

This research explores the development and optimization of Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) for enhancing the oral bioavailability of Furosemide, a widely used diuretic with poor aqueous solubility. The study focuses on the systematic formulation of Furosemide-loaded SNEDDS to overcome the challenges associated with its limited solubility, thereby improving its therapeutic efficacy. the SNEDDS formulations were meticulously designed using various excipients, including oils, surfactants, and co-surfactants, with the goal of achieving a stable and efficient nano emulsion. The selection of these components was based on their compatibility, emulsification capability, and ability to enhance drug solubility. The prepared formulations underwent a comprehensive optimization process employing experimental design methodologies to determine the optimal concentration of each component, ensuring the attainment of a balanced and stable SNEDDS. Physicochemical characterization of the optimized Furosemide SNEDDS was conducted to evaluate its particle size, zeta potential, polydispersity index, and drug-loading capacity. Additionally, the in vitro release profiles were assessed to understand the release kinetics of Furosemide from the SNEDDS. The optimized formulation exhibited favourable characteristics, including a small particle size, high drug-loading efficiency, and sustained drug release, suggesting its potential for improved oral bioavailability. Furthermore, the pharmacokinetic performance of the optimized Furosemide SNEDDS was investigated through in vivo studies, comparing it with conventional Furosemide formulations. The results demonstrated a significant enhancement in the bioavailability of Furosemide when delivered through the SNEDDS, attributed to the increased solubility and improved absorption of the drug. the formulated and optimized Furosemide SNEDDS presents a promising approach to address the solubility challenges associated with Furosemide, offering a potential solution to enhance its oral bioavailability. The study contributes valuable insights into the formulation design and optimization of SNEDDS for poorly water-soluble drugs, paving the way for improved therapeutic outcomes in the pharmaceutical field.

Itraconazole Self-Nano Emusifying Drug Delivery System for Enhancement of Solubility

The main objective of formulation is to enhance the bioavailability of the drug within the body. Some of the challenging subjects associated with poorly water-soluble drugs concern solubility and bioavailability factors. To overcome these problems, new technologies, such as lipid-based drug delivery systems including micro or nano emulsifying drug delivery system, have obtained importance in recent years, due to their enhanced solubility and bioavailability in the gastrointestinal tract. Such systems are solubilized within the lipid excipients or mixed with oils or surfactants/co-solvents to facilitate the solubility and absorption rate, which can enhance the bioavailability of the targeted drug. The research was targeted to develop a self-Nano Emulsifying drug delivery system (SNEDDS) for oral bioavailability enhancement of BCS II antifungal drug Itraconazole. Nano Emulsions are consignment methods that improve the solubility and distribution of lipid medicines to the intended areas. SNEDDS of Itraconazole were developed using Castor oil, Tween 20 as surfactant and PEG 200 as co-surfactant. SNEDDS formulation can be obtained through phase diagram approach. Pseudo Ternary phase diagrams were constructed, using Chemix software, to optimize the concentrations of excipients. Thermodynamic stability studies were satisfactory. Robustness to dilution did not exhibit phase separation and drug precipitation. The Among 4 formulations, B1F3 formulation showed more than 95% of drug content and were considered superior and subjected to droplet size analysis and zeta potential measurement. Droplet size ranged from 120 nm to 505 nm. The Nano size was obtained for formulation. The zeta-potential results indicated the range -35 mV. Based on all evaluation tests, formulation B2F3 was chosen as the best. Thus, this self-Nano Emulsifying drug delivery system should be an effective oral dosage form for improving oral bioavailability of lipophilic drug Itraconazole.

Self-Nano Emulsifying Drug Delivery System: A Potential Solution to the Challenges of Oral Delivery of Poorly Water-Soluble Drugs

Lipid-based drug delivery systems (LBDDS) are the most promising technique to formulate the poorly water soluble drugs. Nanotechnology strongly influences the therapeutic performance of hydrophobic drugs and has become an essential approach in drug delivery research. Self-Nanoemulsifying drug delivery systems (SNEDDS) are a vital strategy that combines benefits of LBDDS and nanotechnology. SNEDDS are now preferred to improve the formulation of drugs with poor aqueous solubility. SNEDDS are isotropic mixtures composed of oils, surfactants, and occasionally cosolvents. The ability of these formulations and methods to produce nanoemulsions or fine oil-in-water (o/w) emulsions after moderate stirring and dilution by water phase along the GI tract. SNEDDS has garnered attention during recent years as it improves oral bioavailability, reduces drug dose, and increases drug protection from unsuitable environment in the gastrointestinal tract. It can solve the problems related to the dissolution and bioavailability of the Biopharmaceutics Classifcation System Class II and IV drugs. This review shortly describes the ambiguity between nanoemulsions and microemulsions, mechanism of self-emulsifications, composition and function of various excipients of SNEDDS. This review discusses characterization of SNEDDS, advantage of SNEEDS over other emulsion, biopharmaceutical aspects, and limitation as well as future views. The SNEDDS is a potential formulation for drug delivery. Owing to its small particle size, large surface area, high encapsulation efficiency, and high drug loading, the SNEDDS can improve the rate and extent of oral absorption by maximizing drug solubility in the intestinal absorption site. Moreover, because of the lipid-based formulation of SNEDDS, it can stimulate and enhance lymphatic transport of drugs to avoid hepatic first-pass metabolism, and thus improve their bioavailability.

FIXED DOSE COMBINATION THERAPY OF IBRUTINIB AND QUERCETIN BY SNEDDS-DEVELOPMENT AND EVALUATION BY DESIGN OF EXPERIMENT

Objective: Self-nano emulsifying drug delivery system (SNEDDS) comprising quercetin and ibrutinib as a fixed dosage combination therapy is being investigated to increase drug solubility and dissolution rate. Methods: On the basis of preliminary solubility tests, castor oil, Kolliphor® RH 40, and PEG600 were utilised to construct ternary phase diagrams. The effect of the amount of Castor oil (A), Kolliphor® RH 40 (B), and PEG600 (C) on the particle size and encapsulation efficiency of ibrutinib and quercetin was evaluated and statistically analysed using multiple regression in 17 trials planned using a 33 Box-Behnken design. FTIR, XRD, DSC, SEM, and stability experiments were employed to characterise the optimised formulation. The particle size, zeta potential, polydispersity index, encapsulation efficiency, and in vitro drug release of ibrutinib and quercetin were also investigated. Results: Ibrutinib and quercetin had encapsulation efficiencies of 61.56-87.22% (Y3) and 60.12-87.12%, respectively, according to the size range of SNEDDS formulations (1-17) of 70.18-200.56 nm. The optimised SNEDDS formulations (S1–S3) showed a particle size range of 71.12–76.38 nm, PDI of 0.126–0.312, zetapotential of-24.6–28.4, and encapsulation efficiencies of 88.98–90.22% and 84.96–86.78% for ibrutinib and quercetin, respectively. According to in vitro testing, the medication released from SNEDDS was released more quickly (&gt;90% 600 min). The formulation was further evaluated using FTIR, XRD, DSC, SEM, and stability investigations, which validated the complexation of ibrutinib and quercetin in the drug's amorphous state and stability for six months. Conclusion: This study revealed that SNEDDS could be used as a drug carrier for ibrutinib and quercetin due to their improved solubility and dissolution rate.

Thymoquinone-loaded self-nano-emulsifying drug delivery system against ischemia/reperfusion injury.

In the present study, a self-nano-emulsifying drug delivery system (SNEDDS) was developed to evaluate the efficiency of thymoquinone (TQ) in hepatic ischemia/reperfusion. SNEDDS was pharmaceutically characterized to evaluate droplet size, morphology, zeta potential, thermodynamic stability, and dissolution/diffusion capacity. Animals were orally pre-treated during 10days with TQ-loaded SNEDDS. Biochemical analyses, hematoxylin-eosin staining, indirect immunofluorescence, and reverse transcription polymerase chain reaction (RT-PCR) were carried out to assess cell injury, oxidative stress, inflammation, and apoptosis. The TQ formulation showed good in vitro characteristics, including stable nanoparticle structure and size with high drug release rate. In vivo determinations revealed that TQ-loaded SNEDDS pre-treatment of rats maintained cellular integrity by decreasing transaminase (ALT and AST) release and preserving the histological characteristics of their liver. The antioxidant ability of the formulation was proven by increased SOD activity, reduced MDA concentration, and iNOS protein expression. In addition, this formulation exerted an anti-inflammatory effect evidenced by reduced plasma CRP concentration, MPO activity, and gene expressions of TLR-4, TNF-α, NF-κB, and IL-6. Finally, the TQ-loaded SNEDDS formulation promoted cell survival by enhancing the Bcl-2/Bax ratio. In conclusion, our results indicate that TQ encapsulated in SNEDDS significantly protects rat liver from I/R injury.

Exploring the Enhanced Antiproliferative Activity of Turmeric Oil and 6-Mercaptopurine in a Combined Nano-Particulate System Formulation.

6-Mercaptopurine (6-MP) is a chemotherapeutic agent with inadequate efficacy due to its poor aqueous solubility and limited bioavailability. Turmeric oil is a naturally occurring bioactive substance obtained from the rhizomes of Curcuma longa Linn that has well-known antiproliferative activities. The aim of this study was to develop a 6-MP-loaded turmeric oil-based self-nanoemulsifying drug delivery system (SNEDDS) to improve the anticancer activity of 6-MP. Turmeric oil was extracted and used in a range of 15-25% to develop SNEDDS formulations utilizing tween 80 and dimethyl sulfoxide as the surfactant and cosurfactant, respectively. The size, charge, and effect of the formulations on the viability against HepG2 and MCF-7 cell models, as well as the apoptosis and cell cycle, were analyzed. The prepared SNEDDS formulations were in the size range of 425.7 ± 7.4-303.6 ± 19.3 nm, using a polydispersity index of 0.429-0.692 and electronegative surface charges. Moreover, 6-MP-loaded SNEDDS with 15% turmeric oil content (F1) showed smaller particle sizes and a noticeable antiproliferative activity against both cell line models. Also, F1 showed a higher rate of late apoptosis than the pure drug and the corresponding non-medicated formulation. A morphological study revealed significant changes in the HepG2 cells compared to untreated cells. More cells halted in the S phase, and a marked decrease in the proportions of cells in the G1/G0 phase was observed when using SNEDDS formulation compared to pure drug. Thus, SNEDDS formulation is a promising drug delivery system for improving the antiproliferative activity of 6-MP, especially when turmeric oil is incorporated.

NANOTECHNOLOGY APPROACH-SELF NANOEMULSIFYING DRUG DELIVERY SYSTEM (SNEDDS)

This review article aims to develop nanotechnology in novel drug delivery systems using self-nano emulsifying drug delivery systems (SNEDDS). This Article was selected using a database with Prism Guideline diagrams. A total of 18 articles obtained from 2010-2020 were used as the primary reference to be analyzed using a systematic review method in the form of meta-synthesis. This review describes the mechanism of SNEDDS in increasing absorption, the components of the SNEDDS formula, the characterization of self-nano emulsifying drug delivery systems (SNEDDS), the effect of the physicochemical properties of SNEDDS on in vivo activity, and the basis for selecting compounds in the SNEDDS formulation. Self-Nanoemulsifying Drug Delivery System (SNEDDS) is a novel drug delivery system from nanoemulsion used to increase the solubility of lipophilic drugs. SNEDDS is an isotropic mixture consisting of oil, surfactant, and co-surfactant. SNEDDS is considered pre-concentrated nanoemulsions or anhydrous forms of nanoemulsions. In SNEDDS, the formation of nanoemulsions occurs when self-nanoemulsions come into contact with gastrointestinal fluids in the presence of light stirring in the peristaltic motion of the gastrointestinal tract. In general, SNEDDS have small particle sizes in the range of 10-200 nm. The application of the self nanoemulsion development system can be used for BCS Class II lipophilic drug compounds and BCS Class IV drugs. SNEDDS is a novel drug delivery system that can be used for oral drug delivery. In occlusion, a self-nanoemulsifying drug delivery system (SNEDDS) is a new approach for the formulation of drug molecules with poor water solubility. Self Nanoemulsifying drug delivery system (SNEDDS) is an isotropic mixture of oil, surfactant, and co-surfactant.

FORMULATION AND OPTIMIZATION OF FUROSEMIDE SNEDDS: A COMPREHENSIVE STUDY

This research explores the development and optimization of Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) for enhancing the oral bioavailability of Furosemide, a widely used diuretic with poor aqueous solubility. The study focuses on the systematic formulation of Furosemide-loaded SNEDDS to overcome the challenges associated with its limited solubility, thereby improving its therapeutic efficacy. the SNEDDS formulations were meticulously designed using various excipients, including oils, surfactants, and co-surfactants, with the goal of achieving a stable and efficient nanoemulsion. The selection of these components was based on their compatibility, emulsification capability, and ability to enhance drug solubility. The prepared formulations underwent a comprehensive optimization process employing experimental design methodologies to determine the optimal concentration of each component, ensuring the attainment of a balanced and stable SNEDDS. Physicochemical characterization of the optimized Furosemide SNEDDS was conducted to evaluate its particle size, zeta potential, polydispersity index, and drug-loading capacity. Additionally, the in vitro release profiles were assessed to understand the release kinetics of Furosemide from the SNEDDS. The optimized formulation exhibited favorable characteristics, including a small particle size, high drug-loading efficiency, and sustained drug release, suggesting its potential for improved oral bioavailability. Furthermore, the pharmacokinetic performance of the optimized Furosemide SNEDDS was investigated through in vivo studies, comparing it with conventional Furosemide formulations. The results demonstrated a significant enhancement in the bioavailability of Furosemide when delivered through the SNEDDS, attributed to the increased solubility and improved absorption of the drug. the formulated and optimized Furosemide SNEDDS presents a promising approach to address the solubility challenges associated with Furosemide, offering a potential solution to enhance its oral bioavailability. The study contributes valuable insights into the formulation design and optimization of SNEDDS for poorly water-soluble drugs, paving the way for improved therapeutic outcomes in the pharmaceutical field.Keywords: Furosemide, SNEDDS, nanoemulsion, formulation, optimization, solubility, bioavailability.

Self-Nanoemulsifying Drug Delivery System for Enhanced Bioavailability of Madecassic Acid: In vitro and in vivo Evaluation.

Madecassic acid (MCA) is a natural triterpenoid isolated from centellae herba that has diverse biological effects, such as anti-inflammatory, antioxidant, and anticancer activities. However, the efficacy of MCA is limited by low oral bioavailability caused by its extremely poor aqueous solubility. This study aimed to develop a self-nanoemulsifying drug delivery system (SNEDDS) for MCA to improve its oral absorption. The utilized oil phases, surfactants, and co-surfactants for SNEDDS were selected based on the solubility of MCA and emulsification efficiency. The optimized formulation was characterized for pharmaceutical properties and its pharmacokinetic behavior was examined in rats. Besides, the intestinal absorption property of MCA was investigated using in situ single-pass intestinal perfusion and intestinal lymphatic transport. The optimized nanoemulsion formula consists of Capryol 90:Labrasol:Kolliphor ELP:Transcutol HP in a weight ratio of 1:2.7:2.7:3.6 (w/w/w/w). MCA-loaded SNEDDS presented a small droplet size (21.52 ± 0.23 nm), with a zeta potential value of -3.05 ± 0.3 mV. Compared with pure MCA, SNEDDS had a higher effective permeability coefficient and showed 8.47-fold and 4.01-fold of maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC), respectively. Cycloheximide was pretreated before the experiment to evaluate the degree of lymphatic uptake. The results showed that cycloheximide greatly influenced the absorption of SNEDDS, resulting in 82.26% and 76.98% reduction in Cmax and AUC, respectively. This study reports the MCA-loaded SNEDDS with distinctly enhanced in vitro and in vivo performance compared with pure MCA and concludes that the SNEDDS formulation could be a viable and effective strategy for improving the dissolution rate and bioavailability of poor aqueous-soluble ingredients.

Formulation and evaluation of ocular self-nanoemulsifying drug delivery system of brimonidine tartrate

The aim of the current study was to develop an ocular Self-nanoemulsifying drug delivery system (SNEDDS) loaded with Brimonidine tartrate (BRT) and evaluate its ex-vivo permeability. SNEDDS loaded with BRT were prepared by low energy method. Physicochemical properties, drug release, ex-vivo permeation, and toxicity studies were investigated. The BRT-loaded SNEDDS formulation was composed of Capmul MCM (Oil), Tween 80 (Surfactant), and Transcutol HP (Co-surfactant) and was optimized by Box-Behnken design. Optimized SNEDDS loaded with BRT had a droplet size of 118.3 nm, a PDI of 0.251, a pH of 6.34 ± 0.31, an osmolarity of 329 mosm/L after reconstitution with NaCl, and a viscosity was found to be 12.39 ± 2.31cP. The optimized SNEDDS loaded with BRT had excellent stability in the shelving period. The apparent permeability coefficient of optimized SNEDDS was found to be (7.078 ± 0.218 × 10−6 cm/s) when compared to the marketed formulation with (3.127 ± 0.173 × 10−6 cm/s). These results suggest that Brimonidine tartrate-loaded SNEDDS can be used as a promising nanocarrier for ocular drug delivery.

The Development and Optimization of Lipid-Based Self-Nanoemulsifying Drug Delivery Systems for the Intravenous Delivery of Propofol.

Propofol is a relatively short-acting potent anesthetic lipophilic drug used during short surgical procedures. Despite the success of propofol intravenous emulsions, drawbacks to such formulations include inherent emulsion instability, the lack of a safe vehicle to prevent sepsis, and concern regarding hyperlipidemia-related side effects. The aim of the current investigation was to develop a novel, lipid-based self-nanoemulsifying drug delivery system (SNEDDS) for propofol with improved stability and anesthetic activity for human use. A series of SNEDDS formulations were developed using naturally obtained medium-chain/long-chain mono-, di-, and triglycerides, glyceryl monocaprylate, and water-soluble cosolvents with hydrogenated castor oil constructing ternary phase diagrams for propofol. The developed SNEDDS formulations were characterized using visual observation, particle size analysis, zeta potential, transmission electron microscopy, equilibrium solubility, in vitro dynamic dispersion and stability, and in vivo sleeping disorder studies in rats. The in vivo bioavailability of the SNEDDSs in rats was also studied to compare the representative formulations with the marketed product Diprivan®. Medium-chain triglycerides (M810) with mono-diglycerides (CMCM) as an oil blend and hydrogenated castor oil (KHS15) as a surfactant were selected as key ingredients in ternary phase diagram studies. The nanoemulsifying regions were identified from the studies and a number of SNEDDSs were formulated. Results from the characterization studies demonstrated the formation of efficient nanosized particles (28-45 nm globule size, 0.10-0.20 PDI) in the optimized SNEDDS with a drug loading of 50 mg/g, which is almost 500-fold higher than free propofol. TEM analysis showed the formation of spherical and homogeneous nanoparticles of less than 50 nm. The dissolution rate of the representative SNEDDS was faster than raw propofol and able to maintain 99% propofol in aqueous solution for around 24 h. The optimized liquid SNEDDS formulation was found to be thermodynamically stable. The intravenous administration of the SNEDDS in male Wistar rats induced a sleeping time of 73-88 min. The mean plasma concentrations after the IV administration of propofol nano-formulations PF2-SNEDDS and PF8-SNEDDS were 1348.07 ± 27.31 and 1138.66 ± 44.97 µg/mL, as compared to 891.44 ± 26.05 µg/mL (p = 0.05) observed after the IV administration of raw propofol. Propofol-loaded SNEDDS formulations could be a potential pharmaceutical product with improved stability, bioavailability, and anesthetic activity.

Unveiling the dielectric properties of self-nanoemulsifying drug delivery systems (SNEDDS)

Self-nanoemulsifying Drug Delivery System (SNEDDS) improves the bioavailability of bioactive compounds that exhibit low water solubility. In this regard, our study aims to assess the formulation of SNEDDS in a wide range of oil concentrations (0–8.6 wt%) by dynamic light scattering, FTIR, dielectric measurements, and the characterization of the interface layer and its molecular interactions with water. The proper formulation of SNEDDS accounted for the lipophilic/hydrophilic balance leading to a homogeneous distribution of oil droplets in water with constant sizes of 20–22 nm, which does not depend on oil concentration. Dielectric spectroscopy measurements in the GHz frequency range allowed us to obtain the dependence of relaxation time as a function of oil concentration and its relationship with the viscosity of the nanoemulsion. The classical two-phase model of Hanai, Maxwell-Garnet, Bruggeman, and Lichtenecker fails to describe the dielectric properties of nanoemulsions. Therefore, in this work, a three-phase model is proposed to model the dielectric measurements, which include water as the continuous phase, oil droplets, and interface layer due to using Cremophor EL (HLB = 12–14) and Labrafil M1944CS (HLB = 2–3) as surfactant and co-surfactant. This model fits well with the experimental results and allows us to obtain SNEDDS properties such as the dielectric constant (20.9), volume fraction, and the interface layer thickness (ca. 5 nm). Investigated oil–water nanoemulsions can be a model for developing different drug delivery systems. Additionally, proposed measurements in the GHz frequency range and their interpretation can be generalized for nanoemulsion characterization.

엔잘루타마이드의 용해도 개선을 위한 고형의 자가나노유화 약물전달시스템

The objective of this study was to develop a novel enzalutamide-loaded solidified self-nanoemulsifying drug delivery system formulation with enhanced solubility and dissolution rate. Various oil and surfactant were screened, then Medium Chain Triglyceride oil and Polysorbate 80 and Labrafil M2125CS were selected as oil and a surfactant. Pseudoternary phase diagram was constructed to detect the nanoemulsion zone. Among the SNEDDS formulations tested, SNEDDS consisted of MCT oil (oil), Polysorbate 80 (surfactant) and Labrafil M2125CS (co-surfactant) at a weight ratio of 20:70:10. The SNEDDS produced the emulsion droplet size 18.66±0.88 nm. Spray drying technique was used to convert the selected enzalutamide-loaded SNEDDS into solid SNEDDS with inert carrier such as silicon dioxide. Enzlautamide-loaded solid SNEDDS was characterized by scanning electron microscopy, transmission electron microscopy, powder X-ray diffractometry, dynamic light scattering, saturation solubility and in vitro dissolution study. The S-SNEDDS produced an emulsion droplet size of 15.37±0.49 nm and there was no change in particle size between with or without drug. SEM and PXRD results suggested that enzalutamide existed in amorphous form in enzalutamide-loaded solid SNEDDS. In addition, enzalutamide-loaded solid SNEDDS increased saturation solubility 42-fold and dissolution rates 23- fold compared to crystalline enzalutamide. Therefore, the solid SNEDDS could be a potential nano-sized drug delivery system for poorly water-soluble drug enzalutamide.

Precision engineering designed phospholipid-tagged pamidronate complex functionalized SNEDDS for the treatment of postmenopausal osteoporosis.

Disodium pamidronate, a second-generation bisphosphonate is a potent drug for the treatment of osteoporosis, which has been very well established by previous literature. It has very low oral permeability, leading to its low oral bioavailability, which restrict this drug to being administered orally. Therefore, the present research work includes the development of an orally effective nanoformulation of pamidronate. In this work, disodium pamidronate was complexed with phospholipon 90G for the enhancement of permeability and to investigate the phospholipon 90G-tagged pamidronate complex-loaded SNEDDS for oral delivery with promises of enhanced bioavailability and anti-osteoporotic activity. The rational design and optimization was employed using Central Composite Design (Design Expert® 12, software) to optimize nanoformulation parameters. In this work, a commercially potential self nano-emulsifying drug delivery system (SNEDDS) has been developed and evaluated for improved oral bioavailability and better clinical acceptance. The hot micro-emulsification and ultracentrifugation method with vortex mixing was utilized for effective tagging of phospholipon 90G with pamidronate and then loading into the SNEDDS nanocarrier. The optimized Pam-PLc SNEDDS formulation was characterized for particle size, PDI, and zeta potential and found to be 56.38 ± 1.37nm, 0.218 ± 0.113, and 22.41 ± 1.14 respectively. Also, a 37.9% improved bioavailability of pamidronate compared to marketed tablet was observed. Similarly, in vivo pharmacokinetic studies suggest a 31.77% increased bone density and significant enhanced bone biomarkers compared to marketed tablets. The developed formulation is safe and effectively overcomes anti-osteoporosis promises with improved therapeutic potential. This work provides very significant achievements in postmenopausal osteoporosis treatment and may lead to possible use of nanotherapeutic-driven emerging biodegradable carriers-based drug delivery.