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Annals of Palliative Medicine Dec 2021The purpose of this study was to evaluate the effects of monovalent and divalent cations on the stability of a fat emulsion (Lipovenoes MCT) in total nutrient admixtures...
BACKGROUND
The purpose of this study was to evaluate the effects of monovalent and divalent cations on the stability of a fat emulsion (Lipovenoes MCT) in total nutrient admixtures (TNAs) by testing the percentage of fat residing in globules >5 µm (PFAT5) values.
METHODS
TNAs with different combinations of glucose (5% and 10%), amino acids (3.35 and 4.5 g/100 mL), Na+/K+ (100/39 mmol/L), Mg2+ (3.4 and 2.7 mmol/L), and fat emulsion (2.4%) were tested in triplicate at room temperature. The pH, mean droplet size (MDS), and PFAT5 were assessed at 0, 6, 12, 24, 36, and 48 h.
RESULTS
In all seven groups, the TNA globule distribution was uniform, the pH value fluctuated in the range of 5.93-6.06, and the MDS met the limit of the United States Pharmacopeia (USP) within 48 h. The PFAT5 value of the control group 0 without electrolytes was the lowest; group 1 added monovalent ions of 139 mmol/L was significantly higher (P<0.05) but without exceed the USP limit after 48 h. Groups 2 and 3 added Mg2+ 3.4 and 2.7 mmol/L respectively, based on group 1. Group 4 increased the amino acid concentration from 3.35% to 4.5% based on group 2, and group 5 reduced the glucose concentration from 10% to 5% based on group 4. Group 6 removed monovalent ions and retained only Mg2+ based on group 5. The PFAT5 values of group 2, 3, 4, and 5 exceeded the limit after 6 h and group 6 after 12 h. There was no statistical difference between group 2 and 4 (P>0.05) or between group 4 and 5 (P>0.05).
CONCLUSIONS
When the concentration of glucose is 10-25% and the amino acid is 2.5-4.5%, The addition of monovalent ions affects the stability of fat emulsion in TNAs, however when the concentrations of Na+ ≤100 mmol/L and K+ ≤39 mmol/L, the PFAT5 value will not exceed the USP limit within 24 h. Mg2+ has a significant effect, the PFAT5 value will exceed the USP limit after 6 h when the concentration ≥2.7 mmol/L, which may cause potential safety hazards.
Topics: Drug Stability; Fat Emulsions, Intravenous; Glucose; Humans; Nutrients; Particle Size
PubMed: 35016476
DOI: 10.21037/apm-21-3353 -
Journal of Materials Chemistry. B Jul 2021Delivering drugs directly into cartilage is still the major challenge in the management and treatment of osteoarthritis (OA) resulting from the aneural, avascular and...
Delivering drugs directly into cartilage is still the major challenge in the management and treatment of osteoarthritis (OA) resulting from the aneural, avascular and alymphatic nature of an articular cartilage structure. Progress has been made in the design of drug delivery systems that enhance corticosteroid uptake and retention in cartilage; however also non-steroidal anti-inflammatory drugs (NSAIDs) are prescribed for patients affected by OA and a drug delivery system specifically designed for this drug category is currently unavailable. We developed an approach based on the preparation of NSAID oil-in-water emulsions coated with poly-beta-amino-esters (PBAEs) to exploit the cartilage penetrating ability of such polymers and the high solubility of drugs in oil. These emulsions containing different NSAIDs (indomethacin, ketorolac, diclofenac and naproxen) exhibited enhanced and prolonged drug localisation not only in healthy cartilage tissues but also in early-stage OA samples. The critical role of the PBAE layer on oil droplets was established along with the retained biological activity of the drug as glycosaminoglycan (GAG) and collagen degradation induced by interleukin-1 (IL-1) was prevented by the novel technology. Oil-in-water coated emulsions are very flexible and cost-effective drug delivery systems and such an approach presented here could provide a substantial improvement in the therapeutic treatments of OA and thus patients' outcomes.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cartilage, Articular; Cattle; Coated Materials, Biocompatible; Drug Carriers; Emulsions; Molecular Structure; Osteoarthritis; Particle Size; Polymers
PubMed: 34254088
DOI: 10.1039/d1tb01024g -
Reproductive Sciences (Thousand Oaks,... Feb 2022A great need exists to develop tocolytic and uterotonic drugs that combat poor, labor-related maternal and fetal outcomes. A widely utilized method to assess novel...
A great need exists to develop tocolytic and uterotonic drugs that combat poor, labor-related maternal and fetal outcomes. A widely utilized method to assess novel compounds for their tocolytic and uterotonic efficacy is the isometric organ bath contractility assay. Unfortunately, water-insoluble compounds can be difficult to test using the physiological, buffer-based, organ bath assay. Common methods for overcoming solubility issues include solvent variation, cosolvency, surfactant or complexion use, and emulsification. However, these options for drug delivery or formulation can impact tissue function. Therefore, the goal of this study was to evaluate the ability of common solvents, surfactants, cosolvents, and emulsions to adequately solubilize compounds in the organ bath assay without affecting mouse myometrial contractility. We found that acetone, acetonitrile, and ethanol had the least effect, while dimethylacetamide, ethyl acetate, and isopropanol displayed the greatest inhibition of myometrial contractility based on area under the contractile curve analyses. The minimum concentration of surfactants, cosolvents, and human serum albumin required to solubilize nifedipine, a current tocolytic drug, resulted in extensive bubbling in the organ bath assay, precluding their use. Finally, we report that an oil-in-water base emulsion containing no drug has no statistical effect beyond the control (water), while the drug emulsion yielded the same potency and efficacy as the freely solubilized drug.
Topics: 2-Propanol; Acetamides; Acetates; Acetone; Acetonitriles; Animals; Emulsions; Ethanol; Female; Mice; Myometrium; Solvents; Tocolytic Agents; Uterine Contraction
PubMed: 33852137
DOI: 10.1007/s43032-021-00576-5 -
Drug Design, Development and Therapy 2023Self-emulsifying drug-delivery systems (SEDDSs) are designed to improve the oral bioavailability of poorly water-soluble drugs. This study aimed at formulating and...
BACKGROUND
Self-emulsifying drug-delivery systems (SEDDSs) are designed to improve the oral bioavailability of poorly water-soluble drugs. This study aimed at formulating and characterization of SEDDS-based tablets for simvastatin using castor and olive oils as solvents and Tween 60 as surfactant.
METHODS
The liquids were adsorbed on microcrystalline cellulose, and all developed formulations were compressed using 10.5 mm shallow concave round punches.
RESULTS
The resulting tablets were evaluated for different quality-control parameters at pre- and postcompression levels. Simvastatin showed better solubility in a mixture of oils and Tween 60 (10:1). All the developed formulations showed lower self-emulsification time (˂200 seconds) and higher cloud point (˃60°C). They were free of physical defects and had drug content within the acceptable range (98.5%-101%). The crushing strength of all formulations was in the range of 58-96 N, and the results of the friability test were within the range of USP (≤1). Disintegration time was within the official limits (NMT 15 min), and complete drug release was achieved within 30 min.
CONCLUSION
Using commonly available excipients and machinery, SEDDS-based tablets with better dissolution profile and bioavailability can be prepared by direct compression. These S-SEDDSs could be a better alternative to conventional tablets of simvastatin.
Topics: Polysorbates; Simvastatin; Emulsions; Drug Delivery Systems; Solubility; Biological Availability; Tablets; Administration, Oral
PubMed: 36726738
DOI: 10.2147/DDDT.S377686 -
Medicine Mar 2024Lipid emulsion has been shown to effectively relieve refractory cardiovascular collapse resulting from toxic levels of nonlocal anesthetics. The goal of this study was... (Review)
Review
Lipid emulsion has been shown to effectively relieve refractory cardiovascular collapse resulting from toxic levels of nonlocal anesthetics. The goal of this study was to examine the effect of lipid emulsions on neuropsychiatric drug-induced toxicity using relevant case reports of human patients, with a particular focus on the Glasgow Coma Scale (GCS) score and corrected QT interval, to analyze drugs that frequently require lipid emulsion treatment. The following keywords were used to retrieve relevant case reports from PubMed: "antidepressant or antipsychotic drug or amitriptyline or bupropion or citalopram or desipramine or dosulepin or dothiepin or doxepin or escitalopram or fluoxetine or haloperidol or olanzapine or phenothiazine or quetiapine or risperidone or trazodone" and "lipid emulsion or Intralipid." Lipid emulsion treatment reversed the corrected QT interval prolongation and decreases in Glasgow Coma Scale scores caused by toxic doses of neuropsychiatric drugs, especially lipid-soluble drugs such as amitriptyline, trazodone, quetiapine, lamotrigine, and citalopram. The log P (octanol/water partition coefficient) of the group which required more than 3 lipid emulsion treatments was higher than that that of the group which required less than 3 lipid emulsion treatments. The main rationale to administer lipid emulsion as an adjuvant was as follows: hemodynamic depression intractable to supportive treatment (88.3%) > lipophilic drugs (8.3%) > suspected overdose or no spontaneous breathing (1.6%). Adjuvant lipid emulsion treatment contributed to the recovery of 98.30% of patients with neuropsychiatric drug-induced toxicity. However, further analyses using many case reports are needed to clarify the effects of lipid emulsion resuscitation.
Topics: Humans; Quetiapine Fumarate; Amitriptyline; Citalopram; Fat Emulsions, Intravenous; Trazodone; Drug-Related Side Effects and Adverse Reactions; Dothiepin
PubMed: 38489675
DOI: 10.1097/MD.0000000000037612 -
AAPS PharmSciTech Jul 2021An emulsion is a biphasic dosage form comprising of dispersed phase containing droplets that are uniformly distributed into a surrounding liquid which forms the... (Review)
Review
An emulsion is a biphasic dosage form comprising of dispersed phase containing droplets that are uniformly distributed into a surrounding liquid which forms the continuous phase. An emulsifier is added at the interface of two immiscible liquids to stabilize the thermodynamically unstable emulsion. Various types of emulsions such as water-in-oil (w-o), oil-in-water (o-w), microemulsions, and multiple emulsions are used for delivering certain drugs in the body. Water (aqueous) phase is commonly used for encapsulating proteins and several other drugs in water-in-oil-in-water (w-o-w) emulsion technique. But this method has posed certain problems such as decreased stability, burst release, and low entrapment efficiency. Thus, a novel "solid-in-oil-in-water" (s-o-w) emulsion system was developed for formulating certain drugs, probiotics, proteins, antibodies, and tannins to overcome these issues. In this method, the active ingredient is encapsulated as a solid and added to an oil phase, which formed a solid-oil dispersion. This dispersion was then mixed with water to form a continuous phase for enhancing the drug absorption. This article focuses on the various studies done to investigate the effectiveness of formulations prepared as solid-oil-water emulsions in comparison to conventional water-oil-water emulsions. A summary of the results obtained in each study is presented in this article. The s-o-w emulsion technique may become beneficial in near future as it has shown to improve the stability and efficacy of the entrapped active ingredient.
Topics: Diclofenac; Drug Carriers; Drug Stability; Emulsions; Microspheres; Nanostructures; Oils; Polylactic Acid-Polyglycolic Acid Copolymer; Proteins; Water
PubMed: 34212274
DOI: 10.1208/s12249-021-02074-y -
BMC Complementary Medicine and Therapies Jan 2023Topical drug delivery using nanoemulsions and nanogels is a promising approach to treating skin disorders such as melanoma.
BACKGROUND
Topical drug delivery using nanoemulsions and nanogels is a promising approach to treating skin disorders such as melanoma.
METHODS
In this study, the chemical composition of Mentha pulegium essential oil with five major compounds, including pulegone (68.11%), l-menthone (8.83%), limonene (2.90%), iso-pulegone (2.69%), and iso-menthone (1.48%) was first identified using GC-MS (Gas chromatography-Mass Spectrometry) analysis. Afterward, a nano-scaled emulsion containing the essential oil with a droplet size of 7.70 ± 1 nm was prepared. Nanogel containing the essential oil was then prepared by adding (2% w/v) carboxymethyl cellulose to the nano-scaled emulsion. Moreover, the successful loading of M. pulegium essential oil in the nano-scaled emulsion and nanogel was confirmed using ATR-FTIR (Attenuated total reflectance-Fourier Transform InfraRed) analysis. Then, human A375 melanoma cells were treated with different concentrations of samples, the MTT assay evaluated cell viability, and cell apoptosis was confirmed by flow cytometry. In addition, the expression of apoptotic and anti-apoptotic genes, including Bax and Bcl-2, was evaluated using the qPCR (quantitative Polymerase Chain Reaction) technique.
RESULTS
The results showed that cell viability was reduced by 90 and 45% after treatment with 300 μg/mL of the nanogel and nano-scaled emulsion. As confirmed by flow cytometry, this effect was mediated by apoptosis. Furthermore, gene expression analysis showed up-regulation of Bax and down-regulation of Bcl-2 genes. Therefore, the prepared nanogel, with high efficacy, could be considered a potent anticancer agent for supplementary medicine and in vivo research.
Topics: Humans; Oils, Volatile; Mentha pulegium; Nanogels; Emulsions; bcl-2-Associated X Protein; Genes, Regulator; Melanoma; Apoptosis
PubMed: 36624422
DOI: 10.1186/s12906-023-03834-y -
Journal of Biomaterials Applications Aug 2021The growth plate is a cartilage tissue near the ends of children's long bones and is responsible for bone growth. Injury to the growth plate can result in the formation...
The growth plate is a cartilage tissue near the ends of children's long bones and is responsible for bone growth. Injury to the growth plate can result in the formation of a 'bony bar' which can span the growth plate and result in bone growth abnormalities in children. Biomaterials such as chitosan microgels could be a potential treatment for growth plate injuries due to their chondrogenic properties, which can be enhanced through loading with biologics. They are commonly fabricated via an emulsion method, which involves solvent rinses that are cytotoxic. Here, we present a high throughput, non-cytotoxic, non-emulsion-based method to fabricate chitosan-genipin microgels. Chitosan was crosslinked with genipin to form a hydrogel network, and then pressed through a syringe filter using mesh with various pore sizes to produce a range of microgel particle sizes. The microgels were then loaded with chemokines and growth factors and their release was studied in vitro. To assess the applicability of the microgels for growth plate cartilage regeneration, they were injected into a rat growth plate injury. They led to increased cartilage repair tissue and were fully degraded by 28 days in vivo. This work demonstrates that chitosan microgels can be fabricated without solvent rinses and demonstrates their potential for the treatment of growth plate injuries.
Topics: Animals; Biocompatible Materials; Cartilage; Chitosan; Disease Models, Animal; Emulsions; Iridoids; Male; Microgels; Rats; Rats, Sprague-Dawley; Regeneration; Salter-Harris Fractures
PubMed: 33709832
DOI: 10.1177/0885328221999894 -
Drug Delivery Dec 2023In present, there was no detailed report on the formulation optimization and quality evaluation of aprepitant (APT) injectable lipid emulsion (APT-IE). The aim of the...
In present, there was no detailed report on the formulation optimization and quality evaluation of aprepitant (APT) injectable lipid emulsion (APT-IE). The aim of the present investigation was to prepare and evaluate its properties of APT-IE loaded with an APT phospholipid complex (APT-PC) and . APT-PC was obtained by solvent evaporation with APT and phospholipids, then analyzed by -ray diffraction, Fourier transform infrared spectroscopy and differential scanning calorimetry. Lipid emulsions are a new formulation that can reduce side effects and improve drug loading.APT-IE prepared by High-pressure homogenization and optimized by response surface methodology (RSM). The proportion of sodium oleate, poloxamer 188 and soybean oil were selected as variables for the optimization. The optimal formulation of ATP-IE had the following characteristics: particle size, 82.83 ± 1.89 nm; polydispersity index, 0.243 ± 0.008; zeta potential, -59.0 ± 2.54 mV; encapsulation efficiency, 98.84%±1.43%; drug loading, 7.08 ± 0.16 mg/mL; and osmotic pressure, 301 ± 2.15 mOsmol/kg. Transmission electron microscopy images indicated that the particle diameter of APT-IE was approximately 100 nm, with a morphology of spheroidal or spherical. APT-IE exhibited sufficient stability after storage at 4 ± 2 °C for more than 6 months. The results of the pharmacokinetic study demonstrated that APT-IE had the advantages of better safety, higher bioavailability, and obvious liver targeting than APT solution (APT-SL). The area under the curve (AUC) of APT-IE was 3-fold enhanced compared with APT-SL. The targeted enhancement multiple of APT-IE to liver tissue was greater than that of APT-SL. These results suggested that APT-IE has broad clinical application and industrial production potential.
Topics: Aprepitant; Phospholipids; Emulsions; Biological Availability; Administration, Intravenous; Particle Size
PubMed: 36843571
DOI: 10.1080/10717544.2023.2183834 -
PloS One 2024This retrospective study aimed to evaluate the effects on the clinical signs of poisoning and adverse effects of intravenous lipid emulsion treatment in 82 animals (dogs...
This retrospective study aimed to evaluate the effects on the clinical signs of poisoning and adverse effects of intravenous lipid emulsion treatment in 82 animals (dogs and cats) with suspected poisonings over 18 months. Physical examination parameters and state of consciousness were documented every hour after the intravenous administration of a bolus of 2 ml/kg and 0.25 ml/kg/min over 60 minutes of a 20% intravenous lipid emulsion. The modified Glasgow coma scale and laboratory findings (blood gas analysis, triglyceride, lactate) were evaluated initially and three hours after discontinuing intravenous lipid emulsion administration. A statistical evaluation of the occurrence of adverse effects and the development of laboratory values was performed. A decrease in respiratory rate in the second control (8-12 hours) after ILE was observed. Three hours after completing of the intravenous lipid emulsion, triglyceride concentration increased about 10 times (p <0.001). Venous carbon dioxide partial pressure, bicarbonate, base excess, as well as the electrolytes sodium, potassium and ionized calcium decreased significantly (p <0.001). Patients who experienced a worsening of the modified Glasgow coma scale had a higher increase in triglyceride concentrations (p = 0.041) and plasma lactate (p = 0.034) and a larger decrease in bicarbonate concentrations (p = 0.053) compared to others. About 54% (n = 44) of the patients showed adverse effects which could be attributed to the administration of intravenous lipid emulsion and may be associated with a higher triglyceride increase. All of them were completely reversible within 33 hours. Adverse effects associated with intravenous lipid emulsion therapy were observed in half of the patients and were associated with a higher increase in triglycerides.
Topics: Animals; Fat Emulsions, Intravenous; Cats; Dogs; Retrospective Studies; Male; Female; Poisoning; Triglycerides; Glasgow Coma Scale; Cat Diseases; Dog Diseases; Blood Gas Analysis
PubMed: 38809887
DOI: 10.1371/journal.pone.0298828