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Self-emulsifying compositions are lipidic drug delivery systems that provide number of delivery advantages. A variety of excipients are available for designing of these drug delivery systems. These systems can be classified as Type I, II, III and IV and alternatively as solid, semisolid and liquid. Till date many patents have been published on self...
Citations
... [46] This solidification process is done by various methods like Adsorption into inert carriers, [72] spray drying, [82] melt granulation, [83] melt-spherization method. [84] ...
... Hot-melt extruders have recently been used to produce solid SEDDS. Several factors, including temperature, flow rate, and recirculation time, need to be adjusted in order to achieve sufficient drug loading and adequate content homogeneity (especially for low-dose drugs) [99]. In the first stage of the multi-stage extrusion spheronization procedure, the liquid SEDDS are mixed with inert solid carriers to create a wet combination mass. ...
... The SNEDDS are disseminated in water containing a suitable carrier, such as mannitol, Aerosil 200, or lactose, while being continuously agitated, to produce a fine O/W emulsion. Drying methods for the finished emulsion include freeze-drying, rotary evaporation, and spraydrying [99]. Yan et al. produced liquid curcumin-SEDDS including lauroglycol Fcc, labrasol, and transcutol HP as oils, surfactants, and co-surfactants, respectively, to solidify curcumin-SEDDS using the spray drying technique [100]. ...
A third of recently created drugs have poor water solubility and absorption. Innovative methods, such as self-nanoemulsifying drug delivery systems (SNEDDS), are being developed to address issues with pharmaceutical delivery and bioavailability. These systems, which are referred to as isotropic mixtures, are made up of the drug, a suitable oil, a surfactant, and either a co-surfactant or co-solvent. These elements combine to create a "oil in water (O/W)" nanoemulsion after being lightly stirred. Colloidal systems, including microemulsions and nanoemulsions, are being used more commonly in food, cosmetics, and pharmaceutical preparations to encapsulate, protect, and transport lipophilic components. The nanoscale particles used in these kinds of delivery systems have a number of potential benefits, including enhanced long-term stability, enhanced solubility, enhanced optical transparency, and enhanced bioavailability. To create SNEDDS, one can utilize a phase diagram technique or a statistical design of trials. For SNEDDS, switching from a liquid to a solid dose form may have improved stability as well as increased patient compliance. The design and production of SNEDDS and their effects on the bioavailability of several medications are the subject of numerous studies that are included in this review.
... Such a transformation combines the benefits of SNEDDS (such as improved solubility and bioavailability) with those of solid dosage forms, i.e., helps reduce production cost, improve formulation stability, simplify manufacturing, allow accurate dosing, and improve patient compliance [22,23]. S-SNEDDS employ various solidification processes, such as adsorption on carriers, [24,25], spray drying [26], melt granulation [27][28][29], and andextrusion-spheronization [30] to integrate liquid or semisolid components into powders. The generated solid SNEDDS can further be formulated into free-flowing powders, granules, pellets, tablets, solid dispersions, microspheres, and nanoparticles [31,32]. ...
... TDL dissolution from manufactured SNECT was compared to L-SNEDDS, DCT, and a commercial product (Cialis TM 2.5 mg, Lilly, LLC, Indianapolis, IN, USA) in 500 mL of 0.1 N HCl buffer dissolution media using a USP Dissolution Tester at 37 • C with a paddle speed of 100 rpm [45,46]. At 5,10,15,30,45,60,90, and 120 min, samples (5 mL) were removed and replaced with equal volumes of fresh medium. To separate undissolved excipients, samples were centrifuged at 6000 rpm for 15 min. ...
This research aimed to develop innovative self-nanoemulsifying chewable tablets (SNECT) to increase oral bioavailability of tadalafil (TDL), a nearly insoluble phosphodiesterase-5 inhibitor. Cinnamon essential oil, PEG 40 hydrogenated castor oil (Cremophor ® RH 40), and polyethylene glycol 400 served as the oil, surfactant, and cosurfactant in the nanoemulsifying system, respectively. Primary liquid self-nanoemulsifying delivery systems (L-SNEDDS) were designed using phase diagrams and tested for dispersibility, droplet size, self-emulsifying capability, and thermodynamic stability. Adsorption on a carrier mix of silicon dioxide and microcrystalline cellulose was exploited to solidify the optimum L-SNEDDS formulation as self-nanoemulsifying granules (SNEG). Lack of crystalline TDL within the granules was verified by DSC and XRPD. SNEG were able to create a nanoemulsion instantaneously (165 nm), a little larger than the original nanoemulsion (159 nm). SNECT were fabricated by compressing SNEG with appropriate excipients. The obtained SNECT retained their quick dispersibility dissolving 84% of TDL within 30 min compared to only 18% dissolution from tablets of unprocessed TDL. A pharmacokinetic study in Sprague–Dawley rats showed a significant increase in Cmax (2.3-fold) and AUC0–24 h (5.33-fold) of SNECT relative to the unprocessed TDL-tablet (p < 0.05). The stability of TDL-SNECT was checked against dilutions with simulated GI fluids. In addition, accelerated stability tests were performed for three months at 40 ± 2 °C and 75% relative humidity. Results revealed the absence of obvious changes in size, PDI, or other tablet parameters before and after testing. In conclusion, current findings illustrated effectiveness of SNECT to enhance TDL dissolution and bioavailability in addition to facilitating dose administration.
... One of the most efficient strategies to improve the oral bioavailability is altering the physical nature of poorly water-soluble lipophilic compounds through its incorporation into lipid vehicle such as oil and selfnanoemulsifying drug delivery systems (SNEDDs) 11,13 . Conventionally, self-emulsifying medicines are liquid formulations filled into capsules or dispensed as oral solutions 14 which results in many disadvantages including lack of stability, irreversible precipitation of excipients/drugs, and leakage of volatile ingredients through the shell of gelatin capsule 15 . The solidification of liquid SNEDDs (L-SNEDDs) through various techniques like: spray drying is a promising approach to surpass the limitations of L-SNEDDs (such as drug precipitation) 16 and combine the benefits of SNEDDs (enhancement of both solubility and bioavailability) with the advantages of solid dosage forms (ease of handling and portability, higher stability and reproducibility, compact dosage form and better patient compliance) 17 . ...
The main purpose of this study was to develop and evaluate solid self-nanoemulsifying drug delivery systems (S-SNEDDs) of Atorvastatin/ Ezetimibe combination to combine the advantages of liquid SNEDDs with those of solid dosage forms and investigate the effect of solidification on both lipid lowering efficiency and the ability to enhance oral bioavailability of included poorly water soluble drugs. Spray dried solid powder was prepared using Aerosil 200 based on its high adsorption capacity and the ratio of liquid SNEDDs: Aerosil was (4:1) due to the smaller droplet size produced after reconstitution compared to other ratios. Surface morphology characteristics and drug-excipients interactions were evaluated via Scanning Electron Microscopy (SEM) and Fourier Transformed Infrared Spectroscopy (FTIR). Crystallinity nature affect drug dissolution so, it was determined by Differential Scanning Calorimetry (DSC) and Powder X-ray Diffraction (PXRD). Pharmacokinetic study investigated the ability of (S-SNEDDS) to improve oral bioavailability of included drugs while, pharmacodynamic study evaluate its efficiency to control serum cholesterol levels compared to pure drugs suspension and liquid SNEDDs. Solid spray dried powder showed very good flowability (3.41±0.23g/s) and rapid dispersion in water with maintaining the self-emulsifying efficiency of liquid formula. Physicochemical evaluation of powder showed spherical separated particles with no significant drug-excipients interactions and drugs are molecularly dispersed or in amorphous state that improve dissolution rate as proven by in-vitro release studies. Pharmacokinetic and pharmacodynamic studies proved that the solidification process had no remarkable effect on the efficiency of liquid formula to enhance oral bioavailability of incorporated drugs and control serum cholesterol level compared to pure drugs suspension. S-SNEDDS was proved as efficient candidate to improve oral bioavailability of Atorvastatin / Ezetimibe combination and control cholesterol serum levels.
... Lecithin is widely used in the pharmaceutical industry as a dispersing, emulsifying, and stabilizing agent [28]. Lecithins are used in formulations meant for intravenous, intramuscular, topical, oral, rectal, and pulmonary administration. ...
Coronavirus disease 2019 (COVID-19), caused by a new strain of coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly worldwide. Nafamostat mesylate (NFM) suppresses transmembrane serine protease 2 and SARS-CoV-2 S protein-mediated fusion. In this study, pharmacokinetics and lung distribution of NFM, administered via intravenous and intratracheal routes, were determined using high performance liquid chromatography analysis of blood plasma, lung lumen using bronchoalveolar lavage fluid, and lung tissue. Intratracheal administration had higher drug delivery and longer residual time in the lung lumen and tissue, which are the main sites of action, than intravenous administration. We confirmed the effect of lecithin as a stabilizer through an ex vivo stability test. Lecithin acts as an inhibitor of carboxylesterase and delays NFM decomposition. We prepared inhalable microparticles with NFM, lecithin, and mannitol via the co-spray method. The formulation prepared using an NFM:lecithin:mannitol ratio of 1:1:100 had a small particle size and excellent aerodynamic performance. Spray dried microparticles containing NFM, lecithin, and mannitol (1:1:100) had the longest residual time in the lung tissue. In conclusion, NFM-inhalable microparticles were prepared and confirmed to be delivered into the respiratory tract, such as lung lumen and lung tissue, through in vitro and in vivo evaluations.
... Most of SNEDDs are in liquid state as major ingredients (oil, surfactants and co-surfactants) used in SNEDDs are usually in liquid state at room temperature. The liquid nature of SNEDDs limits the wide application of such technology for enhancing the oral bioavailability of various drugs because of many disadvantages including lack of stability, large dose volume because of relatively low drug loading capacity, irreversible precipitation of drug and migration of volatile ingredients into shell of gelatin capsule (Memvanga and Préat 2012, Tarate, Chavan et al. 2014). Solidification of Liquid SNEDDS is an efficient strategy to overcome the restrictions of liquid SNEDDS and combine the benefits of SNEDDs (enhancement of both solubility and bioavailability) with the advantages of solid dosage forms (ease of handling and portability, higher stability and reproducibility, compact dosage form and better patient compliance). ...
Self nano emulsifying drug delivery systems (SNEDDs) gained much attention in the last decades since, such systems considered one of the most favorable and efficient approaches to enhance solubility, increase drug absorption and hence, enhance its oral bioavailability of poorly water soluble (lipophilic) drug moieties. Owing to their unique properties and advantages over the other conventional dosage forms, many literatures investigate the change physicochemical properties, pharmacokinetic and pharmacodynamics of self emulsifying formulation compared to both pure drug and its conventional dosage form and always reported significant improvement using SNEDDs. This review discus the composition, advantages and mechanism of action of liquid SNEDDs and some techniques used for solidification of liquid formulations to overcome its drawbacks.
... Generally, the techniques employed to develop solid SNEDDSs include adsorption onto inert carriers [262,263], spray drying [264,265], melt granulation [266,267] and extrusion-spheronization [268] and are described below. ...
Approximately one third of newly discovered drug molecules show insufficient water solubility and therefore low oral bio-availability. Self-nano-emulsifying drug-delivery systems (SNEDDSs) are one of the emerging strategies developed to tackle the issues associated with their oral delivery. SNEDDSs are composed of an oil phase, surfactant, and cosurfactant or cosolvent. SNEDDSs characteristics, their ability to dissolve a drug, and in vivo considerations are determinant factors in the choice of SNEDDSs excipients. A SNEDDS formulation can be optimized through phase diagram approach or statistical design of experiments. The characterization of SNEDDSs includes multiple orthogonal methods required to fully control SNEDDS manufacture, stability, and biological fate. Encapsulating a drug in SNEDDSs can lead to increased solubilization, stability in the gastro-intestinal tract, and absorption, resulting in enhanced bio-availability. The transformation of liquid SNEDDSs into solid dosage forms has been shown to increase the stability and patient compliance. Supersaturated, mucus-permeating, and targeted SNEDDSs can be developed to increase efficacy and patient compliance. Self-emulsification approach has been successful in oral drug delivery. The present review gives an insight of SNEDDSs for the oral administration of both lipophilic and hydrophilic compounds from the experimental bench to marketed products.
... Solid SEDDS as name suggests, are solid dosage forms which have the ability to self-emulsify when come in contact with GI media [37]. S-SEDDS are available in different forms like powders, granules, pellets, tablets and self-emulsifying dispersions [38]. ...
... When this molten mixture is added dropwise with a beaker containing cold water at 4°C at 1000 rpm leads to formation of solid lipid spheres [44]. The granulation process is controlled by the parameters such as impeller speed, mixing time, binder particle size, and viscosity of the molten binder [38]. These can be filtered out and dried. ...
... Factors that affect the size include the orifice size of pneumatic nozzles, temperature of feed and congealing chamber, rate of atomization and air pressure [47]. This method bypasses the use of traditional solvents of spray drying like water and alcohol and relies on the excipients present in typical self-emulsifying formulations [38]. ...
... This system has many advantages, say: Improve patient compliance and palatability since the final product filled into unit dosage form as capsule, (8) protection of drug molecules from invivo hazard condition, (9) enhanced bioavailability through improving the solubilization process, (10) quicker onset of action as the time required reaching tmax is much less in many literatures that compare SEDDS with other conventional dosage form, (11) and predictable therapy due to reduced variability including food effects (12) . SEDDS has some drawbacks that limit its wider applications, from these limitations stability issues, low drug loading and volatile oil migration to gelatin capsule shell are the most frequent (13) . ...
Solubility problem of many of effective pharmaceutical molecules are still one of the major obstacle in theformulation of such molecules. Candesartan cilexetil (CC) is angiotensin II receptor antagonist with very low water solubility and this result in low and variable bioavailability. Self- emulsifying drug delivery system (SEDDS) showed promising result in overcoming solubility problem of many drug molecules. CC was prepared as SEDDS by using novel combination of two surfactants (tween 80 and cremophore EL) and tetraglycol as cosurfactant, in addition to the use of triacetin as oil. Different tests were performed in order to confirm the stability of the final product which includes thermodynamic study, determination of self-emulsification time, particle size and zeta potential measurement, and in-vitro drug release. The results showed that the particle size of the best formula was 13.3 nm and zeta potential of -37.45 mV with approximately 100% release after 45 minutes .These results suggest that the preparation of CC. as SEDDS with the use of the above combination of surfactant and cosurfactant is a promising maneuver for oral delivery of CC. in order to improve its bioavailability.
... The liquid SMEDDS may encounter some problems, like low stability, interaction with the gelatin shell and low drug loading [14]. To overcome some of the problems, solid selfemulsifying/micro emulsifying drug delivery systems (SSEDs/SSMEDs) were developed, having various dosage form options [15,16]. ...
Background:
FR&D scientists continuously try to increase the in vivo performance of low soluble and bioavailable drugs. Solid SMEDDS and liquisolid formulations are relatively simple to develop and fall within the novel drug delivery approaches. Here, a comparison is made to know relative superiority.
Objective:
To conduct comparative pharmacokinetic (PK) and pharmacodynamic (PD) studies of developed Fluvastatin (FLU) solid SMEDDS (SSMED) and liquisolid formulation (LS) for their relative in vivo efficacy.
Method:
FLU liquid SMEDDS were optimized by central composite design (CCD). Components, oil, surfactant and co-surfactant were selected as variables; particle size, self-emulsifying time and % drug release in 15min were selected as responses. L-SMEDDS with positive charge inducer were adsorbed on to porous carriers and characterized. Liquisolid formulations were prepared with Avicel PH-102 and Neusilin US2 as carriers.
Results:
Optimized L-SMEDDS contained 24.92 mg of oil, 45.18 mg of surfactant and 34.28 mg of co-surfactant. SSMEDs containing Syloid XDP (SSMED-XDP) as carrier was selected based on flow properties and liquid retention potential. The average particle size of SSMED-XDP was 154.30±1.10 nm, PDI was 0.311±0.03 and ZP was +19.57±1.34 mV after dilution. The drug release from SSMED-XDP and LS formulations was higher than FLU powder. The bioavailability of SSMEDs was increased by 3.00 fold and that of LS by 1.49 fold more than FLU-suspension. SSMEDs showed 12 h, while LS and suspension showed only 6 h lipid lowering effect.
Conclusion:
The development of solid SMEDDS resulted in superior performance in both PK and PD effects over the LS formulation.
