-
Molecular Pharmaceutics Oct 2021Nanoemulsions are considered as the most promising solution to improve the delivery of ophthalmic drugs. The design of ophthalmic nanoemulsions requires an extensive... (Review)
Review
Nanoemulsions are considered as the most promising solution to improve the delivery of ophthalmic drugs. The design of ophthalmic nanoemulsions requires an extensive understanding of pharmaceutical as well as technological aspects related to the selection of excipients and formulation processes. This Review aims at providing the readers with a comprehensive summary of possible compositions of nanoemulsions, methods for their formulation (both laboratory and industrial), and differences between technological approaches, along with an extensive outline of the research methods enabling the confirmation of properties, pharmaceutical performance, and biological activity of the obtained product. The composition of the formulation has a major influence on the properties of the final product obtained with low-energy emulsification methods. Increasing interest in high-energy emulsification methods is a consequence of their scalability important from the industrial perspective. Considering the high-energy emulsification methods, both the composition and conditions of the process (e.g., device power level, pressure, temperature, homogenization time, or number of cycles) are important for the properties and stability of nanoemulsions. It is advisible to determine the effect of each parameter on the quality of the product to establish the optimal process parameters' range which, in turn, results in a more reproducible and efficient production.
Topics: Administration, Ophthalmic; Emulsions; Eye Diseases; Humans; Nanoparticle Drug Delivery System; Quality Control
PubMed: 34533317
DOI: 10.1021/acs.molpharmaceut.1c00650 -
Drug Delivery Dec 2021Nanogels have high tunability and stability while being able to sense and respond to external stimuli by showing changes in the gel volume, water content, colloidal... (Review)
Review
Nanogels have high tunability and stability while being able to sense and respond to external stimuli by showing changes in the gel volume, water content, colloidal stability, mechanical strength, and other physical/chemical properties. In this article, advances in the preparation of nanogels will be reviewed. The application potential of nanogels in drug delivery will also be highlighted. It is the objective of this article to present a snapshot of the recent knowledge of nanogel preparation and application for future research in drug delivery.
Topics: Chemistry, Pharmaceutical; Cross-Linking Reagents; Drug Carriers; Drug Liberation; Emulsions; Humans; Molecular Weight; Nanogels; Polymers
PubMed: 34308729
DOI: 10.1080/10717544.2021.1955042 -
AACN Advanced Critical Care 2017
Topics: Anesthesia; Drug-Related Side Effects and Adverse Reactions; Fat Emulsions, Intravenous; Humans
PubMed: 28592470
DOI: 10.4037/aacnacc2017454 -
Molecules (Basel, Switzerland) Mar 2023Cefixime (CFX) belongs to a group of third-generation cephalosporin antibiotics with low water solubility and low intestinal permeability, which ultimately leads to...
BACKGROUND
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.
AIM
This study aimed to increase solubility, improve drug release, and intestinal permeability of CFX by loading into SEDDS.
METHODS
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 P of different formulations was compared with the marketed brands of CFX.
RESULTS
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.
CONCLUSION
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.
Topics: Cefixime; Surface-Active Agents; Emulsions; Drug Delivery Systems; Solubility; Drug Liberation; Administration, Oral; Anti-Bacterial Agents; Permeability; Biological Availability; Particle Size
PubMed: 36985803
DOI: 10.3390/molecules28062827 -
International Journal of Pharmaceutics Jun 2023Propofol is the preferred anaesthetic for induction and maintenance of sedation in critically ill mechanically ventilated COVID-19 patients. However, during the outbreak...
Propofol is the preferred anaesthetic for induction and maintenance of sedation in critically ill mechanically ventilated COVID-19 patients. However, during the outbreak of the COVID-19 pandemic, regular supply chains could not keep up with the sudden increase in global demand, causing drug shortages. Propofol is formulated as an oil-in-water emulsion which is administered intravenously. This study explores the extemporaneous preparation of a propofol emulsion without specialized manufacturing equipment to temporally alleviate such shortages. A commercially available lipid emulsion (IVLE, SMOFlipid 20 %), intended for parenteral nutrition, was used to create a propofol loaded nanoemulsion via addition of liquid propofol drug substance and subsequent mixing. Critical quality attributes such as mean droplet size and the volume-weighted percentage of large-diameter (>5µm) droplets were studied. The evolution of droplet size and propofol distribution was monitored in situ and non-destructively, maintaining sterility, using Spatially Resolved Dynamic Light Scattering and Near Infrared Spectroscopy, respectively. Using response surface methodology, an optimum was found for a 4 % w/v propofol formulation with a ∼15 min mixing time in a flask shaker at a 40° shaking angle. This study shows that extemporaneous compounding is a viable option for emergency supply of propofol drug product during global drug shortages.
Topics: Humans; Propofol; Emulsions; Pandemics; COVID-19; Parenteral Nutrition
PubMed: 37061210
DOI: 10.1016/j.ijpharm.2023.122960 -
Food & Function Apr 2021In this study, β-carotene loaded oil-in-water emulsions were stabilized by complex interfaces composed of propylene glycol alginate (PGA), rhamnolipids (Rha), and zein...
In this study, β-carotene loaded oil-in-water emulsions were stabilized by complex interfaces composed of propylene glycol alginate (PGA), rhamnolipids (Rha), and zein colloidal particles (ZCPs). The influence of mixed biopolymer-surfactant, biopolymer-particle, surfactant-particle and biopolymer-surfactant-particle interfaces on the performance of the emulsions was investigated. The stability, microstructure, rheological properties, and in vitro gastrointestinal digestion of the emulsions were controlled by regulating the adding sequence and mass ratio of the multiple stabilizers. The droplet size of the emulsion was in the range of 14-77 μm. After encapsulation into the emulsions stabilized by the complex interfaces, the photothermal stability of β-carotene were increased by 41.53% and 21.52%, respectively. The co-existence of particles, biopolymers, and surfactants could induce competitive displacement, multilayer deposition and an interparticle network at the interface. Compared with a single PGA- or Rha-stabilized emulsion, the complex interface-stabilized emulsion reduced the release of FFA by 28.06% and 26.16%, respectively. The interfacial composition of the emulsion and the delayed lipid digestion further affected the bioaccessibility of β-carotene in the gastrointestinal tract (GIT). The mixed biopolymer-particle-surfactant interface-stabilized emulsion could be incorporated in foods, pharmaceuticals and cosmetics for excellent stability, targeted nutrient delivery and controlled lipolysis.
Topics: Biological Availability; Biopolymers; Digestion; Drug Stability; Elasticity; Emulsions; Gastrointestinal Tract; Microscopy, Electron, Scanning; Particle Size; Pepsin A; Surface-Active Agents; Viscosity; Zein; beta Carotene
PubMed: 33877248
DOI: 10.1039/d0fo02975k -
BMJ Case Reports May 2020A 26-year-old woman presented after an intentional ingestion of 20 g of caffeine. She suffered a profound respiratory alkalosis with metabolic acidosis, hypokalaemia...
A 26-year-old woman presented after an intentional ingestion of 20 g of caffeine. She suffered a profound respiratory alkalosis with metabolic acidosis, hypokalaemia and sustained polymorphic ventricular tachycardia. She was treated with intravenous intralipid and haemodialysis, and her arrhythmia was controlled using magnesium sulphate. Once invasively ventilated and unable to hyperventilate the patient became acidotic and required intravenous bicarbonate to correct her acid-base status. Two days following the overdose the patient was extubated, haemodialysis was stopped and norepinephrine was weaned off. The patient was discharged after a further 7 days. Serial caffeine levels were taken during this patient's care; the highest measured caffeine concentration 7 hours after ingestion was 147.1 mg/L. The known lethal dose of caffeine is 80 mg/L. Intralipid and haemodialysis represent a new and viable treatment in life-threatening caffeine overdose. Intravenous magnesium may terminate unstable arrhythmias in caffeine-poisoned patients.
Topics: Acidosis; Adult; Anti-Arrhythmia Agents; Caffeine; Drug Overdose; Emulsions; Fat Emulsions, Intravenous; Female; Humans; Hypokalemia; Magnesium Sulfate; Phospholipids; Renal Dialysis; Soybean Oil; Suicide, Attempted; Tachycardia, Ventricular
PubMed: 32414776
DOI: 10.1136/bcr-2020-234256 -
Journal of Pharmaceutical Sciences Feb 2019In a typical oil-in-water emulsion drug product, oil droplets with varied sizes are dispersed in a water phase and stabilized by surfactant molecules. The size and...
In a typical oil-in-water emulsion drug product, oil droplets with varied sizes are dispersed in a water phase and stabilized by surfactant molecules. The size and polydispersity of oil droplets are critical quality attributes of the emulsion drug product that can potentially affect drug bioavailability. More critically, to ensure accuracy in characterization of the finished drug product, analytical methods should introduce minimal physical perturbation (e.g., temperature variation or dilution) before the analysis. The classical methods of dynamic light scattering or electron microscopy can be used but they generally require sample dilution or harsh preparation conditions, respectively. By contrast, the size distribution of emulsion formulations can be assessed with a simple and noninvasive solution nuclear magnetic resonance method, namely, two-dimensional Diffusion Ordered SpectroscopY. The two-dimensional Diffusion Ordered SpectroscopY method probed signal decay of methyl resonances from oil and sorbate molecules and was applied to 3 types of U.S.-marketed emulsion drug products, that is, difluprednate, cyclosporine, and propofol, yielding measured droplet sizes of 40-280 nm in diameter. The high precision of ±6 nm of the new nuclear magnetic resonance method allows analytical differentiation of lot-to-lot and brand-to-brand droplet size differences in emulsion drug products, critical for drug-quality development, control, and surveillance.
Topics: Antifungal Agents; Cyclosporine; Diffusion; Emulsions; Fluprednisolone; Glucocorticoids; Hypnotics and Sedatives; Magnetic Resonance Spectroscopy; Oils; Particle Size; Pharmaceutical Preparations; Propofol; Surface-Active Agents; Water
PubMed: 30291851
DOI: 10.1016/j.xphs.2018.09.027 -
Analytical Chemistry Jan 2023Water-in-oil droplet microfluidics promises capacity for high-throughput single-cell antimicrobial susceptibility assays and investigation of drug resistance mechanisms....
Water-in-oil droplet microfluidics promises capacity for high-throughput single-cell antimicrobial susceptibility assays and investigation of drug resistance mechanisms. Every droplet must serve as an isolated environment with a controlled antibiotic concentration in such assays. While technologies for generation, incubation, screening, and sorting droplets mature, predictable retention of active molecules inside droplets remains a major outstanding challenge. Here, we analyzed 36 descriptors of the antibiotic molecules against experimental results on the cross-talk of antibiotics in droplets. We show that partition coefficient and fractional polar surface area are the key physicochemical properties that predict antibiotic retention. We verified the prediction by monitoring growth inhibition by antibiotic-loaded neighboring droplets. Our experiments also demonstrate that transfer of antibiotics between droplets is concentration- and distance-dependent. Our findings immediately apply to designing droplet antibiotic assays and give deeper insight into the retention of small molecules in water-in-oil emulsions.
Topics: Water; Microfluidics; Technology; Emulsions; High-Throughput Screening Assays
PubMed: 36598882
DOI: 10.1021/acs.analchem.2c04644 -
Lab on a Chip Jun 2022Double emulsion droplets (DEs) are water/oil/water droplets that can be sorted fluorescence-activated cell sorting (FACS), allowing for new opportunities in...
Double emulsion droplets (DEs) are water/oil/water droplets that can be sorted fluorescence-activated cell sorting (FACS), allowing for new opportunities in high-throughput cellular analysis, enzymatic screening, and synthetic biology. These applications require stable, uniform droplets with predictable microreactor volumes. However, predicting DE droplet size, shell thickness, and stability as a function of flow rate has remained challenging for monodisperse single core droplets and those containing biologically-relevant buffers, which influence bulk and interfacial properties. As a result, developing novel DE-based bioassays has typically required extensive initial optimization of flow rates to find conditions that produce stable droplets of the desired size and shell thickness. To address this challenge, we conducted systematic size parameterization quantifying how differences in flow rates and buffer properties (viscosity and interfacial tension at water/oil interfaces) alter droplet size and stability, across 6 inner aqueous buffers used across applications such as cellular lysis, microbial growth, and drug delivery, quantifying the size and shell thickness of >22 000 droplets overall. We restricted our study to stable single core droplets generated in a 2-step dripping-dripping formation regime in a straightforward PDMS device. Using data from 138 unique conditions (flow rates and buffer composition), we also demonstrated that a recent physically-derived size law of Wang can accurately predict double emulsion shell thickness for >95% of observations. Finally, we validated the utility of this size law by using it to accurately predict droplet sizes for a novel bioassay that requires encapsulating growth media for bacteria in droplets. This work has the potential to enable new screening-based biological applications by simplifying novel DE bioassay development.
Topics: Emulsions; Flow Cytometry; Surface Tension
PubMed: 35593127
DOI: 10.1039/d2lc00229a