Self-nanoemulsifying Drug Delivery System Research Articles

Recent Progress in the Oral Delivery of Therapeutic Peptides and Proteins: Overview of Pharmaceutical Strategies to Overcome Absorption Hurdles.

Proteins and peptides have secured a place as excellent therapeutic moieties on account of their high selectivity and efficacy. However due to oral absorption limitations, current formulations are mostly delivered parenterally. Oral delivery of peptides and proteins (PPs) can be considered the need of the hour due to the immense benefits of this route. This review aims to critically examine and summarize the innovations and mechanisms involved in oral delivery of peptide and protein drugs. Comprehensive literature search was undertaken, spanning the early development to the current state of the art, using online search tools (PubMed, Google Scholar, ScienceDirect and Scopus). Research in oral delivery of proteins and peptides has a rich history and the development of biologics has encouraged additional research effort in recent decades. Enzyme hydrolysis and inadequate permeation into intestinal mucosa are the major causes that result in limited oral absorption of biologics. Pharmaceutical and technological strategies including use of absorption enhancers, enzyme inhibition, chemical modification (PEGylation, pro-drug approach, peptidomimetics, glycosylation), particulate delivery (polymeric nanoparticles, liposomes, micelles, microspheres), site-specific delivery in the gastrointestinal tract (GIT), membrane transporters, novel approaches (self-nanoemulsifying drug delivery systems, Eligen technology, Peptelligence, self-assembling bubble carrier approach, luminal unfolding microneedle injector, microneedles) and lymphatic targeting, are discussed. Limitations of these strategies and possible innovations for improving oral bioavailability of protein and peptide drugs are discussed. This review underlines the application of oral route for peptide and protein delivery, which can direct the formulation scientist for better exploitation of this route.

Development and optimization of Ropinirole loaded self-nanoemulsifying tablets

BackgroundThe present research work aims to develop a Ropinirole-loaded self-Nanoemulsifying Drug Delivery system. Ropinirole has limited oral bioavailability due to substantial first-pass metabolism, which ultimately results in poor oral bioavailability and reduces plasma drug concentration and an overall reduction in therapeutic effects. Avoiding hepatic first-pass metabolism by increasing lymphatic uptake is the goal of the creation of the Ropinirole Self-NanoEmulsifying System. The solvent system for the liquid Self-NanoEmulsifying Drug Delivery System (SNEDDS) was optimized using Box-Behnken Design, where the concentration of oil(X1), surfactant (X2), and co-surfactant(X3) were taken as independent variables. The formulated liquid SNEDDS were then converted into solid SNEDDS by the adsorption method for improving patient compliance.ResultsThe obtained mean droplet size of the formulated SNEDDS was 96.71 nm, and the rate of emulsification was 22 s. Liquid SNEDDS was converted into solid SNEDDS using Syloid 244 FP as adsorbent. Scanning Electron Microscopy (SEM) study shows well-separated particles adsorbed on Syloid 244 FP. In vitro drug release studies show better release from solid and liquid SNEDDS when compared to pure suspension.ConclusionsRopinirole-loaded SNEDDS can be a better option for reducing the extensive first-pass metabolism associated with Ropinirole.

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.

In Vitro and In Vivo Efficacy of Topical Dosage Forms Containing Self-Nanoemulsifying Drug Delivery System Loaded with Curcumin.

The external use of curcumin is rare, although it can be a valuable active ingredient in the treatment of certain inflammatory diseases. The aim of our experimental work was to formulate topical dosage forms containing curcumin for the treatment of atopic dermatitis. Curcumin has extremely poor solubility and bioavailability, so we have tried to increase it with the usage of self-emulsifying drug delivery systems. Creams and gels were formulated using penetration-enhancing surfactants and gelling agents. The release of the drug from the vehicle and its penetration through the membrane were determined using a Franz diffusion cell. An MTT cytotoxicity and in vitro antioxidant assays were performed on HaCaT cell line. The in vivo anti-inflammatory effect of the preparations was tested by measuring rat paw edema. In addition, we examined the degree of inflammation induced by UV radiation after pretreatment with the cream and the gel on rats. For the gels containing SNEDDS, the highest penetration was measured after half an hour, while for the cream, it took one hour to reach the maximum concentration. The gel containing Pemulen TR-1 showed the highest drug release. It was determined that the curcumin-containing preparations can be safely applied on the skin and have antioxidant effects. The animal experiments have proven the effectiveness of curcumin-containing topical preparations.

Optimization and Validation Test of Self Nano-emulsifiying Drug Delivery System Capsule of Ethanol Extract Parang Romang Leaves

Introdiction: Parang romang contains alkaloids, flavonoids, tannins, and saponins. The secondary metabolites of the leaf extract have low solubility in water. The self-nano emulsifying drug delivery system (SNEDDS) is one solution to increase the solubility of the extract. Aims This study aims to obtain the best formula and ensure that the assay analysis method used can provide accurate and reliable results so that they can be trusted. Methods: Parang romang leaf extract was added to the optimum mixture of tween 20/80, propylene glycol, and olive oil and then characterized including% transmittance, drug loading, emulsification time, particle size, index polydispersity, zeta potential, dissolution test, Scanning electron microscopy (SEM ) and validation of the analysis method including linearity, precision, accuracy, LOD, and LOQ. Result: The results showed the ratio of surfactant, co-surfactant, and olive oil which produced the optimum formula for SNEDDS, namely 26 ml; 17.5 ml; and 6.5 ml,% transmittance 85.90, drug loading 45.36, emulsification time for AGF, AIF, and aqua dest was 15-16 seconds, particle size 404.1 nm, index polydispersity 0.840, zeta potential -31.4 mV, dissolution test 92.13%, SEM in the form of spherical chunks, and the result of the validation test of the analytical method with a linearity of r = 0.9902, precision 0.436%, accuracy 103.738%, LOD 1.87 µ / ml and LOQ 5.57 µ / ml. SNEDDS parang romang leaf extract using olive oil as the oil phase, Tween 80 as a surfactant, and propylene glycol as a cosurfactant provide optimal nanoemulsion characteristics and validation of the analytical method meets the requirements. Conclusion: Formula 1 SNEDDS parang romang leaf extract using olive oil as the oil phase, Tween 80 as a surfactant, and propylene glycol as a cosurfactant is an optimal formula that provides good nanoemulsion characteristics and validation of analytical methods meets the requirements

In Situ Monitoring of Drug Precipitation from Digesting Lipid Formulations Using Low-Frequency Raman Scattering Spectroscopy.

Low-frequency Raman spectroscopy (LFRS) is a valuable tool to detect the solid state of amorphous and crystalline drugs in solid dosage forms and the transformation of drugs between different polymorphic forms. It has also been applied to track the solubilisation of solid drugs as suspensions in milk and infant formula during in vitro digestion. This study reports the use of LFRS as an approach to probe drug precipitation from a lipid-based drug delivery system (medium-chain self-nanoemulsifying drug delivery system, MC-SNEDDS) during in vitro digestion. Upon lipolysis of the digestible components in MC-SNEDDS containing fenofibrate as a model drug, sharp phonon peaks appeared at the low-frequency Raman spectral region (<200 cm-1), indicating the precipitation of fenofibrate in a crystalline form from the formulation. Two multivariate data analysis approaches (principal component analysis and partial least squares discriminant analysis) and one univariate analysis approach (band ratios) were explored to track these spectral changes over time. The low-frequency Raman data produces results in good agreement with in situ small angle X-ray scattering (SAXS) measurements with all data analysis approaches used, whereas the mid-frequency Raman requires the use of PLS-DA to gain similar results. This suggests that LFRS can be used as a complementary, and potentially more accessible, technique to SAXS to determine the kinetics of drug precipitation from lipid-based formulations.

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.

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.

SCREENING OF PIROXICAM SELF-NANOEMULSIFYING DRUG DELIVERY SYSTEM (SNEDDS) USING FRACTIONAL FACTORIAL DESIGN

Piroxicam belongs to BCS class II and has low solubility. Self-nanoemulsifying drug delivery systems (SNEDDS) are considered a potential approach for increasing the solubility and release of piroxicam. This study aimed to select the components and component ratios of piroxicam SNEDDS using fractional factorial design 26-2 (FFD). The variables used in the DFT development of piroxicam SNEDDS are the type and concentration of oil (triacetin and oleic acid), surfactant (kolliphor EL and Tween 60), and co-surfactants (Transcutol and PEG 400). The FFD results showed 16 runs with different proportions of the piroxicam SNEDDS components, which were then characterized by critical parameters including emulsification time, %transmittance, droplet size, and drug loading. The components and component ratios of the PKM SNEDDS were determined using single-factor plot analysis. The results showed that triacetin (oil), kolliphor EL (surfactant), Transcutol (co-surfactant) had the greatest contribution to the formation of piroxicam SNEDDS with an oil ratio range of 11.11–28.57%, surfactant 44.44–77.78%, co-surfactant 11.11–44.44 %.

Development of positively charged amphiphile containing self-nanoemulsifying drug delivery system for improved therapeutic efficacy of metronidazole against Helicobacterpylori

Metronidazole (MTZ) has been extensively used to treat bacterial infections for over five decades, but MTZ bacterial resistance has been on the rise, making it less effective against Bacteroides species. This study aimed to improve the antibacterial activity of MTZ-loaded self-emulsifying drug delivery systems (SNEDDS) against H. pylori by the incorporation of alkylated morpholine serving as a positively charged amphiphile. The studies of drug solubility and emulsification led to the development of a ternary phase diagram for selecting formulation ingredients. The key ingredients of the formulation were selected as cinnamon oil (lipid), cremophor EL (surfactant), and polyethylene Glycol (PEG) 200 (co-surfactant). The optimized formulations were characterized for various physicochemical properties. The average droplet size and zeta potential of MTZ-SNEDDS were determined to be 146.03 ± 2.1 nm and −15.3 ± 0.50 mV while for alkylated morpholine incorporated MTZ-SNEDDS, these were 183.36 ± 21.42 nm and −16.2 ± 1.30 mV, respectively. The thermodynamically robust alkylated morpholine incorporated SNEDDS was successful in maintaining the chemical integrity of the MTZ. The antibacterial potential of MTZ-SNEDDS was significantly enhanced against H. pylori upon the incorporation of alkylated morpholine. It can be concluded that incorporating amphiphilic positively charged morpholine into SNEDDS can lead to more intake of them by H. pylori, and prolonging the contact duration of the SNEDDS with the outer membrane of H. pylori increased the transmembrane penetration of SNEDDS.

Development and Characterization of Bosentan Monohydrate-loaded Self-Nano Emulsifying Drug Delivery System

Aim/ Objective: The present investigation aims to develop a solid Self-nano emulsifying Drug Delivery System for enhancing the solubility and in vitro characteristics of poorly soluble an-ti-hypertensive drug Bosentan Monohydrate. Methods: The selection of formulation components on the basis of equilibrium solubility and pseu-do-ternary phase titration studies revealed the suitability of Isopropyl myristate, Tween 80 and Pol-yethylene glycol as the lipidic excipients and their optimized concentration ranges resulted in a sta-ble microemulsion region. Results: The systematic optimization of the liquid SNEDD formulations of Bosentan was per-formed using in vitro tests and detailed characterization studies. The results revealed that the F4 formulation produces excellent results and satisfactory results in all the CQA of liquid SNEDDS. The optimized liquid SNEDD formulations exhibited globule size of less than 100 nm, high and negative values of zeta potential, quick self-emulsification rate, negligible phase separation, and a high degree of physical stability during thermodynamic evaluation studies. SEM revealed nanostructured particles with negligible aggregation. Conclusion: In vitro dissolution studies of Bosentan in optimized liquid SNEDDS (F4) unveiled a multi-fold enhancement in release profile, as compared to pure API.

3D Printing Technology as a Promising Tool to Design Nanomedicine-Based Solid Dosage Forms: Contemporary Research and Future Scope.

3D printing technology in medicine is gaining great attention from researchers since the FDA approved the first 3D-printed tablet (Spritam®) on the market. This technique permits the fabrication of various types of dosage forms with different geometries and designs. Its feasibility in the design of different types of pharmaceutical dosage forms is very promising for making quick prototypes because it is flexible and does not require expensive equipment or molds. However, the development of multi-functional drug delivery systems, specifically as solid dosage forms loaded with nanopharmaceuticals, has received attention in recent years, although it is challenging for formulators to convert them into a successful solid dosage form. The combination of nanotechnology with the 3D printing technique in the field of medicine has provided a platform to overcome the challenges associated with the fabrication of nanomedicine-based solid dosage forms. Therefore, the major focus of the present manuscript is to review the recent research developments that involved the formulation design of nanomedicine-based solid dosage forms utilizing 3D printing technology. Utilization of 3D printing techniques in the field of nanopharmaceuticals achieved the successful transformation of liquid polymeric nanocapsules and liquid self-nanoemulsifying drug delivery systems (SNEDDS) to solid dosage forms such as tablets and suppositories easily with customized doses as per the needs of the individual patient (personalized medicine). Furthermore, the present review also highlights the utility of extrusion-based 3D printing techniques (Pressure-Assisted Microsyringe-PAM; Fused Deposition Modeling-FDM) to produce tablets and suppositories containing polymeric nanocapsule systems and SNEDDS for oral and rectal administration. The manuscript critically analyzes contemporary research related to the impact of various process parameters on the performance of 3D-printed solid dosage forms.

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.

Mannosylated preactivated hyaluronic acid-based nanostructures for bacterial infection treatment

Salmonella Typhi is an intracellular bacterium causing a variety of enteric diseases, being typhoid fever the most common. Current modalities for treating S. typhi infection are subjected to multi-drug resistance. Herein, a novel macrophage targeting approach was developed via coating bioinspired mannosylated preactivated hyaluronic acid (Man-PTHA) ligands on a self-nanoemulsifying drug delivery system (SNEDDS) loaded with the anti-bacterial drug ciprofloxacin (CIP). The shake flask method was used to determine the drug solubility in the different excipients (oil, surfactants and co-surfactants). Man-PTHA were characterized by physicochemical, in vitro, and in vivo parameters. The mean droplet size was 257 nm, with a PDI of 0.37 and zeta potential of −15 mV. In 72 h, 85 % of the drug was released in a sustained manner, and the entrapment efficiency was 95 %. Outstanding biocompatibility, mucoadhesion, muco-penetration, anti-bacterial action and hemocompatibility were observed. Intra-macrophage survival of S. typhi was minimal (1 %) with maximum nanoparticle uptake, as shown by their higher fluorescence intensity. Serum biochemistry evaluation showed no significant changes or toxicity, and histopathological evaluation confirmed the entero-protective nature of the bioinspired polymers. Overall, results confirm that Man-PTHA SNEDDS can be employed as novel and effective delivery systems for the therapeutic management of S. typhi infection.

Formulation and Statistical Evaluation of Tablets Containing Pitavastatin- Self Nano Emulsifying Drug Delivery Systems.

To formulate and characterize tablets containing Pitavastatin that have been loaded with a self-nano emulsifying drug delivery system (SNEDDS). Pitavastatin SNEDDS were prepared with a variety of oils, surfactants, co-surfactants, and solvents to improve the dissolution rate and bioavailability of the HMG-CoA reductase inhibitor. The SNEDDS components were preliminarily investigated for drug solubility in various vehicles, excipient miscibility, emulsification rate, and ternary phase diagrams. The tablets were made using a porous carrier made of Aerosil 200 and then loaded with SNEDDS using a simple absorption method. Physical parameters such as tablet hardness, weight variation, disintegration, drug content, and in-vitro drug release were then measured on the tablets. Labrafac Lipophilewl1349 (Oil), Tween 80 (Surfactant) and Egg lecithin (Co-surfactant) were selected for the preparation of SNEDDS. Tablets with high porosity suitable for loading with SNEDDS and containing the super-disintegrants, achieved complete dissolution of Pitavastatin from the tablets. In vitro release of Pitavastatin from SNEDDS and the tablets was similar (p < 0.05). SNEDDS of Pitavastatin is a promising approach to achieving a solid dosage form of the liquid-loaded drug delivery systems for enhancing the solubility and dissolution rate of the drug, and hence also its 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.

Effectiveness of Snedds (Self-Nanoemulsifying Drug Delivery System) Etil Acetate Fraction of Kadara Fruit (Caesalpinia bonduc) Seed Extract on Bacteria Diabetic Gangreen

High glucose level conditions cause many fatal complications, such as the increased risk of developing gangrene. The incidences of amputation worldwide have happened of 25% and 14.3% mortality after amputation. Patients with diabetic gangrene are often treated with a broad-spectrum antibiotic. However, nowadays antibiotic-resistant bacteria are emerging problems to cure the infection in diabetic gangrene. Scientists are looking for natural compounds to develop new medication as an alternative antibacterial. Kadara (Caesalpinia bonduc) is a plant from Dompu, West Nusa Tenggara. Flavonoids, the primary constituent of Caesalpinia bonduc seeds, are responsible for broad-spectrum antibacterial action. Flavonoids are poorly soluble in water, so as the solution for increasing the stability of flavonoids, it needs development of dosage form in the self-nanoemulsion drug delivery system (SNEDDS). This study aims to determine the effectiveness of the Snedds ethyl acetate fraction of the extract of the seeds of the fruit (Caesalpinia bonduc) against diabetic gangrene bacteria. This research begins with maceration to obtain a thick extract followed by fractionation, then make the SNEDDS formula using the trial-error method. Characterization is carried out, and the antibacterial activity test is carried out. The results showed that the SNEDDS formula that met the criteria was obtained from a comparison of tween 80 and PEG 400 (7:2) with an emulsification time of 29.67±0.58 seconds, a transparent emulsion formation medium, and a particle size of 16.8nm. The results of the bacterial inhibition test showed that the SNEEDS formula was not significantly different from the tetracycline positive control (*p&gt;0.05), with the inhibitory diameter values of 15.67±2.31mm and 15.67±1.15mm.

Incorporating valsartan in sesame oil enriched self-nanoemulsifying system-loaded liquisolid tablets to improve its bioavailability

Valsartan (VST) is a poorly soluble antihypertensive drug characterized by its limited dissolution rate and low bioavailability. This study aims to improve VST solubility and dissolution rate via developing liquisolid tablets (LSTs) containing a self-nanoemulsifying drug delivery system (SNEDDS), which is expected to enhance VST bioavailability. This aim was achieved via two designs of experiment. The first was the simplex-lattice design to optimize VST-loaded-SNEDDS using sesame oil, Tween 80, and polyethylene glycol 400. The second was the 32-3-level factorial design to optimize the liquisolid system using the SNEDDS-loaded VST and Neusilin®US2 as a carrier and fumed silica as a coating material. Different excipient ratios (X1) and varioussuper-disintegrants (X2) were also used in developing the optimized VST-LSTs. Thein vitrodissolution of VST from LSTs was compared with the marketed product (Diovan®). Non-compartmental analysis of plasma data after extravascular input with the linear trapezoidal method was used to calculate thepharmacokinetic parameters of the optimized VST-LSTs compared with the marketed tablet in male Wistar rats. The optimized SNEDDS compromised 24.9% sesame oil, 33.3% surfactant, and 41.8% cosurfactant, giving 173.9 nm size and 63.9 mg/ml loading capacity. Also, the SNEDDS-loaded VST tablet revealed good quality attributes with the release of 75% of its content in 5 min and 100% within 15 min. On the other hand, the marketed product took 1 h for the entire drug to be released.Moreover, the maximum plasma concentration (Cmax) of the optimizedVST-LSTwas6585.33 ng/ml within 1 h (Tmax), compared to 2884.67 ng/ml within 2 h of the marketed tablet.The relative bioavailability of the SNEDDS-loaded VST tablet was 213.7% compared to that of the marketed tablet, indicating that this formulation approach could be applied for increasing solubility, dissolution behavior in GIT, and bioavailability of poorly water-soluble drugs.

Self-nanoemulsifying drug delivery system (SNEDDS) of docetaxel and carvacrol synergizes the anticancer activity and enables safer toxicity profile: optimization, and in-vitro, ex-vivo and in-vivo pharmacokinetic evaluation.

Docetaxel (DTX) is a first-line chemotherapeutic molecule with a broad-spectrum anticancer activity. On the other hand, carvacrol (CV) has anti-inflammatory, antioxidant, cytotoxic, and hepatoprotective properties that could reduce undue toxicity caused by DTX chemotherapy. Thus, in order to overcome the challenges posed by DTX's poor aqueous solubility, low permeability, hepatic first pass, and systemic toxicities, we have developed a novel solid self-nanoemulsifying drug delivery system (S-SNEDDS) co-loaded with DTX and CV. In the present investigation, liquid-SNEDDS (L-SNEDDS) were fabricated using Nigella sativa oil, Cremophor RH 40, and Ethanol which was converted into solid by lyophilization using Aerosil 200. The reconstituted CV-DTX-S-SNEDDS showed an average globule size of < 200nm with promising flow properties (angle of repose θ: 33.22 ± 0.06). Additionally, 2.3-fold higher dissolution of DTX was observed from CV-DTX-S-SNEDDS after 6h as compared to free DTX. Similar trend was followed in dialysis release experiments with 1.5-fold higher release within 24h. Ex vivo permeation studies demonstrated significantly increased permeation of 1077.02 ± 12.72μg/cm2 of CV-DTX-S-SNEDDS after 12h. In vitro cell cytotoxicity studies revealed 5.2-fold reduction in IC50 as compared to free DTX in MDA-MB-231 cells. Formulation was able to induce higher apoptosis in cells treated with CV-DTX-S-SNEDDS as compared to free DTX and CV. It was evident from toxicity studies that CV-DTX-S-SNEDDS was well tolerated at higher dose where CV was able to manage the toxic effects of free DTX. In vivo pharmacokinetic study showed 3.4-fold increased Cmax and improved oral bioavailability as compared to free DTX. Thus, CV-DTX-S-SNEDDS could be an encouraging option for facilitating DTX oral therapy.

Formulation Development, Optimization, and Characterization of Entrectinib-Loaded Supersaturable Self-Nanoemulsifying Drug Delivery Systems

Formulation Development, Optimization, and Characterization of Entrectinib-Loaded Supersaturable Self-Nanoemulsifying Drug Delivery Systems