Emulsification Efficiency Research Articles

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.

Surface Wettability-Switchable Janus Fiber Fragments Stabilize Pickering Emulsions for Effective Oil/Water Separation.

Pickering emulsions indicate stronger resistance against droplet coalescence than the surfactant-stabilized emulsions. To resemble the surfactant amphiphilicity, Janus fiber fragments (JFs) were herein prepared through side-by-side electrospinning of poly(styrene-maleic anhydride) (PSMA) derivatives and cryosection of the aligned fibers, followed by conjugation of hydrophobic cetylamine (C16) and hydrophilic poly(N-isopropylacrylamide) (PNIPAm) ligands on the separate sides. Orthogonal analysis table L25(56) was designed to examine the effect of process parameters on the emulsification efficiency and stability index of Pickering emulsions. The emulsification efficiency is dominated by the JF concentration and length, while the emulsion stability could be prolonged through adjusting the JF concentration and hydrophilic graft density. JF-stabilized emulsions exhibit a much higher stability index (96.4%) than that of Janus microparticle counterparts (37.7%). Though there is no apparent effect on the surface wettability, JFs with PNIPAm grafts of about 2200 Da achieve the most stable Pickering emulsions. Superparamagnetic Fe3O4 nanoparticles are inoculated into JFs to collect emulsion droplets under a magnetic field, and the emulsions could be demulsified at an elevated temperature to harvest oil. Meanwhile, the recovered JF emulsifiers could be repeatedly used without loss of the emulsification efficiency. Thus, this study demonstrates surface-switchable JFs to be effective stabilizers of Pickering emulsions and readily recycled for oil harvesting from wastewater.

Screening and selection of formulation components of nanostructured lipid carriers system for Mitragyna Speciosa (Korth). Havil drug delivery

Nanostructured lipid carriers (NLC) have evolved as effective vehicles for improving the bioavailability of poorly water-soluble drugs as well as protecting them from degradation and metabolism. The present study investigated the preformulation and its impact on different liquid lipids and solid lipids with diverse chemical structures and hydrophilic-lipophilic balance (HLB) for the critical quality attributes of Mitragyna speciosa leaves extract (MS)-based nanostructured lipid carriers suitable for drug delivery system. The presence of bioactive alkaloids (mitragynine, 7-hydroxymitragynine, speciogynine), flavonoids (quercetin, apigenin, kaempferol), saponins (daucosterol, quinovic acid 3-o-beta-d-quinovopyranoside, 1-o-feruloyl-beta-d-glucose), and other bioactive phytochemicals (chlorogenic acid, umbelliferone, ursolic acid) in MS leaves extract was detected using LCMS/MS analysis to support its medicinal properties. The total phenolic content, total flavonoid content, and DPPH assay of MS were 90.88 ± 0.30 GAE mg/g, 50.43 ± 0.47 QE mg/g, and IC50 at 0.0397 ± 0.0035 mg/mL, respectively. The screening preparation of NLC requires the selection of liquid lipid (oil), solid lipid, and surfactant. Based on the solubility test, the maximum solubility of MS leaves extract in oleic acid (liquid lipid) and compritol ATO 888 (solid lipid) were 2.859 ± 0.010% and 53.02 ± 0.39% respectively at ratio 70:30. Tween 80 was selected as the main surfactant for the preparation of NLC due to its highest emulsification efficiency (51.53%). The antimicrobial study showed that MS leaves extract gives antimicrobial effect towards Streptococcus aureus bacteria. The preformulation information collected offers a better, efficient, and cost-effective choice for further formulation development of MS leaves extract in drug delivery systems.

Enhanced Intestinal Permeability of Cefixime by Self-Emulsifying Drug Delivery System: In-Vitro and Ex-Vivo Characterization.

Cefixime (CFX) belongs to a group of third-generation cephalosporin antibiotics with low water solubility and low intestinal permeability, which ultimately leads to significantly low bioavailability. This study aimed to increase solubility, improve drug release, and intestinal permeability of CFX by loading into SEDDS. Suitable excipients were selected based on drug solubility, percent transmittance, and emulsification efficiency. Pseudo-ternary phase diagram was fabricated for the identification of effective self-emulsification region. The best probably optimized formulations were further assessed for encumbered drug contents, emulsification time, cloud point measurement, robustness to dilution, mean droplet size, zeta potential, polydispersity index (PDI), and thermodynamic and chemical stability. Moreover, in vitro drug release studies and ex vivo permeation studies were carried out and apparent drug permeability Papp of different formulations was compared with the marketed brands of CFX. Amongst the four tested SEDDS formulations, F-2 formulation exhibited the highest drug loading of 96.32%, emulsification time of 40.37 ± 3 s, mean droplet size of 19.01 ± 1.12 nm, and demonstrated improved long-term thermodynamic and chemical stability when stored at 4 °C. Release studies revealed a drug release of 97.32 ± 4.82% within 60 min in simulated gastric fluid. Similarly, 97.12 ± 5.02% release of CFX was observed in simulated intestinal fluid within 120 min; however, 85.13 ± 3.23% release of CFX was observed from the marketed product. Ex vivo permeation studies displayed a 2.7-fold increase apparent permeability compared to the marketed product in 5 h. Owing to the significantly improved drug solubility, in vitro release and better antibacterial activity, it can be assumed that CFX-loaded SEDDS might lead to an increased bioavailability and antibacterial activity, possibly leading to improved therapeutic effectiveness.

PH- and Redox-Responsive Pickering Emulsions Based on Cellulose Nanocrystal Surfactants.

Nanoparticle surfactants (NPSs), formed by using dynamic interactions between nanoparticles and complementary ligands at the liquid-liquid interface, have emerged as "smart emulsifiers" with attributes of high emulsification efficiency, long-term stability, and on-demand emulsification/demulsification capabilities. However, only pH-responsiveness can be adopted for the assembly of reported NPSs formed by electrostatic interactions. Here, we propose an alternative design strategy, by taking advantage of the ferrocenium (Fc+ ) sulfate ion pair, to develop a new type of cellulose nanocrystal (CNC) surfactant. The Fc+ groups are sensitive to pH, redox reagents and voltage, imparting the CNC surfactants and derived Pickering emulsions with multi-stimuli-responsiveness, and showing promising applications in controllable delivery, release, and biphasic biocatalysis.

PH‐ and Redox‐Responsive Pickering Emulsions Based on Cellulose Nanocrystal Surfactants

AbstractNanoparticle surfactants (NPSs), formed by using dynamic interactions between nanoparticles and complementary ligands at the liquid‐liquid interface, have emerged as “smart emulsifiers” with attributes of high emulsification efficiency, long‐term stability, and on‐demand emulsification/demulsification capabilities. However, only pH‐responsiveness can be adopted for the assembly of reported NPSs formed by electrostatic interactions. Here, we propose an alternative design strategy, by taking advantage of the ferrocenium (Fc+) sulfate ion pair, to develop a new type of cellulose nanocrystal (CNC) surfactant. The Fc+ groups are sensitive to pH, redox reagents and voltage, imparting the CNC surfactants and derived Pickering emulsions with multi‐stimuli‐responsiveness, and showing promising applications in controllable delivery, release, and biphasic biocatalysis.

Potential of lignin multifunctionality for a sustainable skincare: Impact of emulsification process parameters and oil-phase on the characteristics of O/W Pickering emulsions

Colloidal lignin particles (CLPs) from softwood kraft lignin were evaluated as a multifunctional ingredient to prepare bio-based oil-in-water (O/W) Pickering emulsions. After a preliminary screening, three Pickering emulsions systems were formulated using orange, coconut, and paraffin oils, at varying concentration of CLPs, oil/water ratio, and by applying two-step homogenisation processes (rotor-stator homogenisation followed by ultrasonication). Ultrasonication as a second homogenisation step considerably enhanced the emulsification efficiency, generating emulsions with smaller droplet size and less polydisperse distribution. Furthermore, the effect of ultrasonication on the characteristics of emulsions and the stability of the systems was evaluated over time. The oil content and type, the concentration of CLPs, and the homogenisation methods significantly influenced the characteristics of the emulsions and drop size. Higher concentrations of oil and CLPs favoured the formation of the emulsion and contributed to higher physical stability after 120 days of monitoring. The in vitro Sun Protection Factor (SPF) results demonstrated that the incorporation of natural oils containing phenolic compounds in Pickering formulations improves the SPF value of emulsions, showing an interesting synergic effect between lignin particles and vegetable oils, which was not observed in the case of paraffin oil. Furthermore, the broad-spectrum sun blocker of Pickering emulsions was confirmed by the values of UVA/UVB between 0.74 and 0.90 and Cλ > 380.

Construction of Janus silicon carbide membranes with asymmetric wettability for enhanced antifouling in water-in-oil emulsification process

Given that the membrane emulsification process involves the interaction between the membrane surfaces and two different phases (i.e., oil and water), separately manipulating the wettability of each surface would be crucial to achieve the high emulsification efficiency. Herein, the Janus silicon carbide (SiC) membranes were designed and prepared by using an emerging reactive sintering method and the subsequent chemical grafting modification on one of the hydrophilic surfaces. The surface wettability was selectively controlled by using hexadecyltrimethoxysilane (HDTMS) and 1H, 1H, 2H, 2H-perfluorooctyltrichlorosilane (FOTS) as the hydrophobic or amphiphobic modifiers, respectively. Meanwhile, the modified side of Janus SiC membranes showed super-hydrophobicity under oil. It was found that the hydrophobic surface can inhibit the spread of water on membrane surface and the oleophobic surface can reduce the pollution of the membrane, which both affected the membrane emulsification performance. The water-in-oil (W/O) emulsions with mean water droplet size of 1.26–1.57 μm can be prepared using amphiphobic-hydrophilic Janus membranes at a high emulsification flux (1910 L·m−2·h−1). Importantly, the pure water permeance only declined 15.6% of the original value after three times of membrane emulsification. Moreover, the polluted membranes can be easily and effectively regenerated by ultrasonic cleaning in ethanol with a flux recovery ratio of 95.8%. Therefore, the amphiphobic Janus SiC membranes showing improved anti-fouling ability can be effectively utilized in the emulsification of high-viscosity oil.

Enhancing the interfacial stability of O/W emulsion by adjusting interactions of chitosan and rice protein hydrolysate

The influences of chitosan and rice protein hydrolysate (CH/RH) ratio and oil-water ratio on the emulsification efficiency, as well as the impact of RH on the formation of CH/RH complex coacervates was investigated. Emulsions prepared by CH/RH at different concentrations (1–4%) were also evaluated. Higher proportion of CH led to an increase in turbidity, ζ-potential, and particle size and a decrease in surface hydrophobicity of CH/RH. The ζ-potential and droplet sizes of CH/RH stabilized emulsions increased with increasing CH proportion at different oil-water ratios. The formation of strong network due to electrostatic interaction between CH and RH, possessing amphiphilicity contributed by hydrophobicity of RH and hydrophilicity of CH, improve emulsion stability. The CH/RH complexes at ratio of 1:1 can form more stable emulsion as oil volume fraction from 20% to 80%. CH/RH 1:1 emulsion had greater viscosity and storage/loss modulus values than other CH/RH complexes, followed by CH/RH 1:2 at oil fraction ≥50%. Higher oil fraction (60% and 80%) enhanced the viscosity while decreased the emulsion storage stability. Increasing CH/RH concentration can help to form a thicker and stronger interfacial layer on the droplets and a more stable network structure, thus enhancing emulsion stability. Overall, CH/RH 1:1 is more effective in enhancing the interfacial adsorption and emulsification stability than CH or RH alone, especially at 50% oil volume fraction. This study may contribute to the potential of CH/RH complexes for stabilizing emulsion system at different oil contents applied in different food formulations.

Synthesis of high-toughness waterborne polyurethane utilizing self-emulsifying CO2-based polyols

In this work, a self-emulsifying CO2-based polyol (LAPEC) was prepared by the terpolymerization of propylene oxide, allyl glycidyl ether and CO2, followed by thiol-ene click reaction with mercaptopropionic acid. And the carboxyl group was successfully introduced into LAPEC verified in 1H NMR. LAPEC was served as both soft segments and internal emulsifiers for WPU. Meanwhile, γ-aminopropylmethyldiethoxysilane (KH902) was also employed to improve the mechanical properties of WPU. Compared to dimethylol propionic acid (DMPA), WPU emulsion prepared by LAPEC had smaller particle size and higher emulsification efficiency. And the performance differences between LAPEC-based WPU films (LWPUs) and DMPA-based WPU films (DWPUs) with different hard segment contents were studied. The stronger hydrogen-bonding interactions improved the tensile strength, toughness and thermal stability. Compared with DWPU, the tensile strength and the elongation at break of LWPU respectively increased from 17.8 to 21.1 MPa and from 302.3 % to 356.5 %, when their hard segment content was both maintained around 37 wt%. Meanwhile, due to rougher surfaces and more hydrophobic silicon clusters, LWPU had stronger surface hydrophobicity. Therefore, LAPEC can provide a new way to synthesize WPU with high toughness and can be potentially used for flexible substrate coatings in the future.

Formulation of oily tocotrienols as a solid self-emulsifying dosage form for improved oral bioavailability in human subjects

Self-emulsifying drug delivery systems (SEDDS) have been shown to enhance the water-solubility and oral bioavailability of poorly water-soluble compound. Solid SEDDS (s-SEDDS) address the stability and compatibility issues associated with conventional liquid SEDDS, but have limitations including the use high amounts of surfactants and complex processes resulting in low final drug loading and poor powder flow. The aim of the present study was to formulate a solid dosage form containing 100 mg tocotrienols using the optimized s-SEDDS powder we developed with tocotrienol-rich fraction (TRF) as the model liquid active substance via a simple adsorption method. The s-SEDDS granules formulated via wet-granulation with PVP K30 showed excellent flow properties, retained good emulsification efficiency, with submicron emulsion droplet size and dissolution profile of 75–100%. The oral bioavailability evaluated in human subjects showed that of the s-SEDDS capsules was comparable absorption to that of the commercial liquid self-emulsifying product Tocovid Suprabio™, which demonstrated enhanced tocotrienols’ bioavailability by 3-fold compared to that of an oily non self-emulsifying preparation. In conclusion, the bioavailability of tocotrienols from the s-SEDDS was encouraging and can be a promising alternative and a convenient solid dosage form that can significantly enhance the oral bioavailability of the tocotrienols.

Improved thermal and oxidation stabilities of pickering high internal phase emulsions stabilized using glycated pea protein isolate with glycation extent

The development of food grade high internal phase emulsions (HIPEs) stabilized by plant protein-based particles has attracted widespread attention due to their potential applications in food, cosmetic, and biomedical fields. This work reported that glycation with glucose progressively improved the emulsification efficiency of pea protein isolate (PPI) in a glycation extent manner. The physicochemical and structural properties of glycated PPI (gPPI) products with different glycation extent of 0%–36.69% were characterized. The glycation with increasing glycation extent led to a decrease in particle diameter ranging from 157.53 nm to 115.77 nm, while the three-phase contact angle remarkably increased from 54.85° to 79.62°. In addition to emulsification efficiency, glycation progressively facilitated protein adsorption at the interface and defined interfacial structure. The improved thermal and oxidation stability of gPPI by increasing glycation extent was largely attributed to enhanced conformation flexibility that also facilitated formation of bridged emulsions. These findings are important for developing PPI-based Pickering stabilizers for HIPEs and improving insight on modified emulsifying properties of gPPI via glycation extent.

A pH-controlled curcumin-loaded emulsion stabilized by pea protein isolate-maltodextrin-epigallocatechin-3-gallate: Physicochemical properties and in vitro release properties

To improve emulsification properties of pea protein isolate (PPI), PPI-maltodextrin-epigallocatechin-3-gallate (PPI-MD-EGCG) ternary conjugate was prepared for the first time by glycation and then covalent reaction under alkaline conditions. According to structural and physicochemical analysis of PPI-MD-EGCG ternary conjugate by circular dichroism, fluorescence spectroscopy, and Fourier transform infrared spectroscopy, PPI-MD-EGCG ternary conjugate showed the lowest peak intensity and surface hydrophobicity, while the highest emulsification and DPPH radical scavenging efficiency. These confirmed that interactions among protein, saccharide, and polyphenol destroyed the secondary structures of PPI. This may be that combination of glycation and covalent reaction can increase the unfolded conformation and the disordered secondary structures of proteins. PPI-MD-EGCG ternary conjugate was applied in curcumin-loaded emulsion based on ternary conjugate and linoleic acid containing curcumin. Potential of this ternary conjugate as a pH-controlled delivery and release system as well as bioaccessibility of curcumin were evaluated. Curcumin-loaded ternary conjugate emulsion showed the highest loading efficiency of 92.3% and stability. In vitro release properties suggested this ternary conjugate might be a good pH-controlled carrier for curcumin. Therefore, PPI-MD-EGCG ternary conjugate could be used as an effective delivery and release system.

Study of the spontaneous nano-emulsification process with different octadecyl succinic anhydride derivatives

Three new amphiphilic molecules were synthetized on a basis of a common monomer, octadecyl succinic anhydride (OSA), on which were grafted different PEGylated hydrophilic polar head. The objective of this study is to investigate a potential relationship between the chemical structure of the surfactant, and the efficiency to generate nano-emulsions through the spontaneous nano-emulsification method. Beyond the innovative synthesis and comparison of these amphiphiles, a comprehensive comparison is suggested, comparing size distribution and polydispersity for the different composition parameters, as well making a bridge with critical micelle concentration and hydrophile lipophile balance (HLB). Using OSA monomeric entity as common hydrophobic moiety, the variations in the surfactant molecules were done on the hydrophilic moiety, through the addition of one or two Jeffamine chains in different configurations, so-called C18⊖-PEG, C18-PEG and C18-PEG2. The results disclosed that C18⊖-PEG allows producing smallest size distribution and lowest PDI values. Moreover, C18⊖-PEG presents the highest critical micellar concentration, linked to a higher hydrophilicity of the molecule. This impacts the balance between surfactant affinity for oil and aqueous phases, a point probably related to the spontaneous emulsification efficiency. A last part of the study regarded the optimization of the emulsification efficiency, through a systematic study in ternary composition map, to disclosed that the best conditions are included in the lower surfactant concentrations, for water and oil contents higher and lower than 50%, respectively. The main idea behind this study was to bring further insights into the unclear relationship between the chemical structure of nonionic surfactants, and the efficiency of the emulsification by spontaneous low-energy method.

Predicting nanoemulsion formulation and studying the synergism mechanism between surfactant and cosurfactant: A combined computational and experimental approach

Nanoemulsion (NE) is a dosage form widely used in pharmaceutical, food, agrochemical, cosmetics, and personal care industries. NE systems are usually formulated through trial and error via numerous semi-empirical experiments. Moreover, the complex interaction mechanisms between the formulation surfactant and cosurfactant are difficult to understand. Dissipative particle dynamics (DPD) may be helpful in solving these formulation problems. Silibinin is a flavonolignan isolated from milk thistle, which has demonstrated antioxidant and antimicrobial effects. For this project, silibinin-loaded nanoemulsion (SBNE) was formulated by DPD, including surfactant and cosurfactant screening, pseudo-ternary phase construction, and SBNE characterization, all of which were verified by experimentation. Most importantly, this work shows that DPD can be adopted to explore the synergetic mechanisms between the surfactant and cosurfactant, including emulsification efficiency, distance, angle, arrangement, and order parameter. Additional verification experiments on the antioxidant and antimicrobial applications of simulation-designed SBNE were also carried out and confirmed DPD-predicted results. As such, predicting NE formulation by DPD has been proven to be feasible. For SBNE, the addition of PEG400 cosurfactant stretches the Cremophor RH40 surfactant molecules and assists in a more orderly arrangement. An enhanced interfacial thickness in SBNE could be attributed to the stretched hydrophilic head group and the decreased angle between the molecular axis and interface normal. These DPD and experimentally-verified results indicated that a proper cosurfactant will enhance the interfacial thickness, decrease the consumption of surfactant, and benefit NE formation. This new computationally applied knowledge should facilitate optimizing, designing, and understanding NE formulation more rationally and scientifically.

Defibrillated microcrystalline cellulose as an efficient emulsion stabilizer – Study of food-grade Pickering emulsions resistant to extreme conditions

Natural and sustainable Pickering emulsion stabilizers are gaining increased popularity in various fields, especially in the food industry and plant-based alternative sector. However, suitable biocompatible and food-grade stabilizers are scarce, have limited emulsification efficiency, and their stability has only been tested under mild environmental conditions. In this work, mechanically defibrillated microcrystalline cellulose (dMCC) was characterized and assessed for its emulsifying efficiency under extreme conditions that simulate industrial production processes. Food-grade dMCC-based Pickering emulsions produced with commercial canola or coconut oil, at an oil concentration of up to 50%, demonstrated exceptional stability under long-term storage (6 months) and after standard sterilization treatment (121 °C at 210 kPa). This was demonstrated by measurements of emulsion droplet diameter, rheological characteristics, and zeta-potential values, which remained unchanged over time of despite the harsh conditions applied. Furthermore, polarized microscopy revealed that dMCC particles accumulated over time on the emulsion droplet surface, which might explain the high stability of the emulsions. These findings suggest that dMCC is a robust emulsifier that can be applied with various types of oils to produce stable Pickering emulsions, resistant to harsh production conditions. Taken together, dMCC can therefore be incorporated in commercial applications where plant-based, sustainable, and efficient Pickering stabilizers are required.

Formulation and Evaluation of Solid Self-Nanoemulsifying Drug Delivery System for Enhancing the Solubility and Dissolution Rate of Budesonide

Objective: To enhance solubility and dissolution rate of budesonide through development of solid self-nanoemulsifying drug delivery system (S-SNEDDS). Methods: Liquid self-nanoemulsifying drug delivery systems (L-SNEDDS) were prepared and ternary phase diagram was constructed using Origin pro 8. Liquid self-nanoemulsifying formulation LF2 having 20% oil and 80% of surfactant/co-surfactant was optimized from the three formulations (LF1-LF3) to convert in to solid, through various characterization techniques like self-emulsification, in vitro drug release profile and drug content estimation. The prepared L-SNEDDS converted into S-SNEDDS, SF1-SF6 by adsorption technique using Aerosil 200, Neusilin US2, and Neusilin UFL2 to improve flowability, compressibility and stability. Results: Formulation LF2 exhibited globule size of 82.4 nm, PDI 0.349 and Zeta potential -28.6 mV with drug indicating the stability and homogeneity of particles. The optimized formulation SF4 containing Neusilin UFL2 was characterized by DSC, FTIR, X-Ray diffraction studies and found no incompatibility and no major shifts were noticed. Formulation SF4 released 100 % drug in 20 min against pure drug release of 47 % in 60 min. Regardless of the form (i.e. liquid or solid) similar performance of emulsification efficiency is observed. Conclusion: The results demonstrated that the technique of novel solid self-nanoemulsifying drug delivery system can be employed to enhance the solubility and dissolution rate of poorly water-soluble drug budesonide.

In Vitro Evaluation of a Solid Supersaturated Self Nanoemulsifying Drug Delivery System (Super-SNEDDS) of Aprepitant for Enhanced Solubility.

Aprepitant (APR) belongs to Class II of the Biopharmaceutical Classification System (BCS) because of its low aqueous solubility. The objective of the current work is to develop self-nanoemulsifying drug delivery systems (SNEDDS) of APR to enhance its aqueous solubility. Preformulation studies involving screening of excipients for solubility and emulsification efficiency were carried out. Pseudo ternary phase diagrams were constructed with blends of oil (Imwitor® 988), cosolvent (Transcutol® P), and various surfactants (Kolliphor® RH40, Kolliphor® ELP, Kolliphor® HS15). The prepared SNEDDS were characterized for droplet size and nanoemulsion stability after dilution. Supersaturated SNEDDS (super-SNEDDS) were prepared to increase the quantity of loaded APR into the formulations. HPMC, PVP, PVP/VA, and Soluplus® were used as polymeric precipitation inhibitors (PPI). PPIs were added to the formulations at 5% and 10% by weight. The influence of the PPIs on drug precipitation was investigated. In vitro lipolysis test was carried out to simulate digestion of formulations in the gastrointestinal tract. Optimized super-SNEDDS were formulated into free-flowing granules by adsorption on the porous carriers such as Neusilin® US2. In vitro dissolution studies of solid super-SNEDDS formulation revealed an increased dissolution rate of the drug due to enhanced solubility. Consequently, a formulation to improve the solubility and potentially bioavailability of the drug was developed.

Development and Evaluation of Micro Emulsion Formulations of Nebivolol for Solubility Enhancement

Nebivolol HCl is a newer drug of β1-adrenergic blocker category, basically used as anti-hypertensive. It is a 3rd generation, antagonist, having NO (nitric oxide) enhancing vasodilator properties. It has 12% oral bioavailability, because of its pre systemic metabolism by the means of cytochrome P450 2D6 enzymes. Its log P value is 4.03 and 5mg is its daily dose. It is highly lipophilic drug and belongs to class BCS II, with slow dissolution. Bioavailability of any drug can be improved by avoiding its first pass metabolism and promoting solubility. Several researchers have worked on the development of ME formulations on different poor water-soluble drugs, to increase their solubility. The purpose of this study is an attempt to enhance the solubility to improve the bioavailability of nebivolol drug by developing a novel delivery system that is microemulsion (ME) .ME formulations were developed using different oil, surfactant and co-surfactants in different ratio and studied on various parameters. Different preformulation tests done on received sample of Nebivolol. FTIR study was performed in order to find out any interactions between the ingredients. Based on the solubility Capmul Pg-12 was finalized oil, Tween 80 as surfactant, propylene glycol as the cosurfactant based on solubility and emulsification efficiency. Five Nebivolol ME formulations were successfully developed by use of oil, water, SA and Co-SA different ratio. Prepared formulations were studied for different properties- transmittance (%), pH, refractive index, viscosity, drug content, and solubility. It was seen that after 4 hours of diffusion, the drug released from the formulation ME5 is faster and more than that of the other i.e., 90.2±0.06%. It was found that ME5 was more stable and Soluble than other prepared formulations. With the better solubilty the bioavailability of Nebivolol will increased and helps in faster absorption and High diffusion in systemic circulation with lower or no risk of degradation. It somehow also reduced frequent intake of drug.
 Keywords: Nebivolol, micro emulsion, Ternary phase diagram, surfactant, co-surfactant.

Effect of ethanol on the stability of sodium caseinate stabilised emulsions

Proteins are commonly used as emulsifying agent in food applications, although they are highly affected by their environment, with the presence of ethanol being just one parameter known to influence their properties. An increasing level of ethanol is expected to result in a reduced emulsification efficiency of the protein and, therefore, emulsion processing in the absence of this solvent should lead to more stable oil-in-water emulsions. Sodium caseinate was either dispersed in the presence or absence of heat and/or ethanol and multiple physicochemical properties of the resulting protein aggregates were determined. Further, oil-in-water emulsions were created in a microfluidizer at varying levels of ethanol in the aqueous phase and two different points of its addition in the processing route. The resulting emulsion properties were investigated. Stable oil-in-water emulsions could be prepared at each applied ethanol level (≤50 wt%) and for both examined processing routes. The point of ethanol addition only had an impact if the concentration of this solvent was higher than 25 wt% - with a processing in absence of ethanol being beneficial. This concentration was also found to be a threshold for the interactions between ethanol and dispersed sodium caseinate as higher ethanol levels resulted in significantly changed protein properties.