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Chemical & Pharmaceutical Bulletin 2023Itraconazole, a commonly used antifungal drug in the clinic approved by U.S. Food and Drug Administration (FDA), has been gradually found to have anti-tumor,...
Itraconazole, a commonly used antifungal drug in the clinic approved by U.S. Food and Drug Administration (FDA), has been gradually found to have anti-tumor, angiogenesis inhibition and other pharmacological activities. However, its poor water solubility and potential toxicity limited its clinical application. In order to improve the water solubility and reduce the side effects caused by the high concentration of itraconazole, a novel preparation method of itraconazole sustained release microspheres was established in this study. Firstly, five kinds of polylactic acid-glycolic acid (PLGA) microspheres loaded with itraconazole were prepared by oil/water (O/W) emulsion solvent evaporation and then characterized by infrared spectroscopy. Then the particle size and morphology of the microspheres were observed by scanning electron microscope (SEM) and transmission electron microscope (TEM). After that, the particle size distribution, drug loading rate, entrapment efficiency, and drug release experiments were evaluated. Our results showed the microspheres prepared in this study had uniform particle size distribution and good integrity. Further study found that the average drug loading of the five kinds of microspheres prepared with PLGA 7505, PLGA 7510, PLGA 7520, PLGA 5020 and PLGA 0020 were 16.88, 17.72, 16.72, 16.57, and 16.64%, respectively, and the encapsulation rate all reached about 100%. More surprisingly, the release experimental results showed that the microspheres prepared with PLGA 7520 did not show sudden release, showing good sustained release performance and high drug release rate. To sum up, this study optimized the preparation method of sustained-release microspheres without sudden release, which provides a new solution for the delivery of itraconazole in the clinic.
Topics: Polylactic Acid-Polyglycolic Acid Copolymer; Polyglycolic Acid; Lactic Acid; Delayed-Action Preparations; Itraconazole; Microspheres; Emulsions; Solvents; Particle Size
PubMed: 37394601
DOI: 10.1248/cpb.c22-00747 -
Drug Delivery Dec 2021To evaluate the enhancement of temozolomide (TMZ) delivery in the rat brain using a triolein emulsion.
PURPOSE
To evaluate the enhancement of temozolomide (TMZ) delivery in the rat brain using a triolein emulsion.
MATERIALS AND METHODS
Rats were divided into the five groups as following: group 1 (negative control), group 2 (treated with triolein emulsion and TMZ 20 mg/kg), and group 3 (TMZ 20 mg/kg treatment without triolein), group 4 (treated with triolein emulsion and TMZ 10 mg/kg), and group 5 (TMZ 10 mg/kg treatment without triolein). Triolein emulsion was infused into the right common carotid artery. One hour later, the TMZ concentration was evaluated quantitatively and qualitatively using high-performance liquid chromatography (HPLC-MS) and desorption electrospray ionization mass spectrometry (DESI-MS) imaging, respectively. The concentration ratios of the ipsilateral to contralateral hemisphere in each group were determined and the statistical analysis was conducted using an unpaired -test.
RESULTS
Quantitatively, the TMZ concentration ratio of the ipsilateral to the control hemisphere was 2.41 and 1.13 in groups 2 and 3, and were 2.49 and 1.14 in groups 4 and 5, respectively. Thus, the TMZ signal intensities of TMZ in group 2 and 4 were statistically high in the ipsilateral hemispheres. Qualitatively, the signal intensity of TMZ was remarkably high in the ipsilateral hemisphere in group 2 and 4.
CONCLUSIONS
The triolein emulsion efficiently opened the blood-brain barrier and could provide a potential new strategy to enhance the therapeutic effect of TMZ. HPLC-MS and DESI-MS imaging were shown to be suitable for analyses of enhancement of brain TMZ concentrations.
Topics: Animals; Antineoplastic Agents, Alkylating; Blood-Brain Barrier; Brain; Chemistry, Pharmaceutical; Dose-Response Relationship, Drug; Drug Delivery Systems; Emulsions; Male; Rats; Rats, Sprague-Dawley; Temozolomide; Triolein
PubMed: 34747271
DOI: 10.1080/10717544.2021.1998247 -
Molecules (Basel, Switzerland) Oct 2020Polyphenols are micronutrients that are widely present in human daily diets. Numerous studies have demonstrated their potential as antioxidants and anti-inflammatory... (Review)
Review
Polyphenols are micronutrients that are widely present in human daily diets. Numerous studies have demonstrated their potential as antioxidants and anti-inflammatory agents, and for cancer prevention, heart protection and the treatment of neurodegenerative diseases. However, due to their vulnerability to environmental conditions and low bioavailability, their application in the food and medical fields is greatly limited. Nanoformulations, as excellent drug delivery systems, can overcome these limitations and maximize the pharmacological effects of polyphenols. In this review, we summarize the biological activities of polyphenols, together with systems for their delivery, including phospholipid complexes, lipid-based nanoparticles, protein-based nanoparticles, niosomes, polymers, micelles, emulsions and metal nanoparticles. The application of polyphenol nanoparticles in food and medicine is also discussed. Although loading into nanoparticles solves the main limitation to application of polyphenolic compounds, there are some concerns about their toxicological safety after entry into the human body. It is therefore necessary to conduct toxicity studies and residue analysis on the carrier.
Topics: Drug Delivery Systems; Emulsions; Liposomes; Metal Nanoparticles; Nanoparticles; Polyphenols
PubMed: 33050462
DOI: 10.3390/molecules25204613 -
European Journal of Pharmaceutical... Oct 2017The knowledge and experiences obtained with oral phospholipid excipients is increasing continuously. Nevertheless the present number of oral products using these... (Review)
Review
The knowledge and experiences obtained with oral phospholipid excipients is increasing continuously. Nevertheless the present number of oral products using these excipients as essential excipient is very limited. This is remarkable to note, since phospholipids play a significant role in the food uptake mechanisms of the GI tract and these mechanisms could be translated into suitable dosage forms and corresponding drug delivery strategies. In addition, phospholipid excipients are multifunctional biodegradable, non-toxic excipients, which can be used in oral dosage forms as wetting agents, emulsifier, solubilizer and matrix forming excipients. Especially natural phospholipid excipients, made from renewable sources, may be considered as environmentally friendly excipients and as a viable alternative to synthetic phospholipid and non-phospholipid analogues. This review describes 1) essential physico-chemical properties of oral phospholipid excipients 2) the fate of orally administered phospholipids with respect to absorption and metabolism in the GI tract 3) the main dosage forms used for oral administration containing phospholipids. These elements are critically assessed and areas of future research of interest for the use of oral phospholipid excipients are summarized.
Topics: Administration, Oral; Chemistry, Pharmaceutical; Drug Delivery Systems; Emulsions; Excipients; Humans; Micelles; Molecular Structure; Phospholipids; Solubility; Structure-Activity Relationship
PubMed: 28711714
DOI: 10.1016/j.ejps.2017.07.008 -
Scientific Reports Dec 2021The aim of the present study was to formulate clindamycin (CLN) as a microsponge based gel to release the drug in a controlled manner and reduce the side effects in the...
The aim of the present study was to formulate clindamycin (CLN) as a microsponge based gel to release the drug in a controlled manner and reduce the side effects in the treatment of acne. Since this method requires poor water solubility of the drug to be loaded in particles, therefore, conversion of the hydrochloride salt to free base was done. By using an emulsion solvent diffusion method, we made six different formulations of microsponges containing CLN-free base by changing the proportions of polymer, emulsifier and the pH of the external phase. These formulations were studied for physical characterization and for drug- polymer interactions. The physical characterization showed that microsponge formulations coded by C5, C6 resulted in a better loading efficiency and production yield and their particle size was less than 30 µm. Scanning electron microscopy images showed the microsponges porous and spherical. C5, C6 microsponge formulation was prepared as gel in Carbopol and in vitro evaluated. The microsponge formulation gel C8 was found to be optimized. C8 released 90.38% of drug over 12 h and showed viscosity 20,157 ± 38 cp, pH of 6.3 ± 0.09 and drug content of 99.64 ± 0.04%. Fourier transform infrared spectroscopy and differential scanning calorimetry confirmed no significant interactions between excipients and drug.
Topics: Anti-Bacterial Agents; Clindamycin; Drug Delivery Systems; Emulsifying Agents; Emulsions; Gels; Polymers; Solubility
PubMed: 34857863
DOI: 10.1038/s41598-021-02826-7 -
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 -
Journal of Oleo Science 2022Herein, we report the colloidal stability of emulsifier-free (EF-) triolein-in-water (TO/W) emulsions prepared by mixing TO and water using a high-powered bath-type...
Herein, we report the colloidal stability of emulsifier-free (EF-) triolein-in-water (TO/W) emulsions prepared by mixing TO and water using a high-powered bath-type ultrasonicator (HPBath-US; 28 kHz, 300 W) in the absence of emulsifiers such as surfactants. In particular, the effect of the temperature (15-60℃) on the colloidal stability of EF-TO/W emulsions was examined because this is important for the practical application of EF-TO/W emulsions, for example, in foods, pharmaceuticals, and cosmetics. We found that the colloidal stability of the EF-TO/W emulsions decreased with increase in the temperature from 15 to 25°C, whereas it increased with increase in temperature from 25 to 40°C, and the high colloidal stability of the EF-TO/W emulsions was maintained above 40°C. The reduction in the colloidal stability of EF-TO/W emulsions between 15 and 25°C is likely a result of the TO droplets formed by thermal motion, as well as enhanced Ostwald ripening at higher temperatures. On the other hand, the increase in the colloidal stability of the EF-TO/W emulsions from 25 to 40°C and their high colloidal stability above 40℃ is attributed to the reduction in the interfacial tension between TO and water at higher temperatures. This decrease in the interfacial tension between TO and water with temperature increase is related to the transformation of short-range ordered domains (clusters) of TO molecules in the liquid state, which increases the colloidal stability of the EF-TO/W emulsions.
Topics: Colloids; Cosmetics; Drug Stability; Emulsifying Agents; Emulsions; Food; Pharmaceutical Preparations; Surface-Active Agents; Temperature; Triolein; Ultrasonics; Water
PubMed: 35013039
DOI: 10.5650/jos.ess21234 -
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