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Electrophoresis Nov 2021The electrophoresis and electric conduction of a suspension of charged spherical particles in a salt-free solution are analyzed by using a unit cell model. The...
The electrophoresis and electric conduction of a suspension of charged spherical particles in a salt-free solution are analyzed by using a unit cell model. The linearized Poisson-Boltzmann equation (valid for the cases of relatively low surface charge density or high volume fraction of the particles) and Laplace equation are solved for the equilibrium electric potential profile and its perturbation caused by the imposed electric field, respectively, in the fluid containing the counterions only around the particle, and the ionic continuity equation and modified Stokes equations are solved for the electrochemical potential energy and fluid flow fields, respectively. Explicit analytical formulas for the electrophoretic mobility of the particles and effective electric conductivity of the suspension are obtained, and the particle interaction effects on these transport properties are significant and interesting. The scaled zeta potential, electrophoretic mobility, and effective electric conductivity increase monotonically with an increase in the scaled surface charge density of the particles and in general decrease with an increase in the particle volume fraction, keeping each other parameter unchanged. Under the Debye-Hückel approximation, the dependence of the electrophoretic mobility normalized with the surface charge density on the ratio of the particle radius to the Debye screening length and particle volume fraction in a salt-free suspension is same as that in a salt-containing suspension, but the variation of the effective electric conductivity with the particle volume fraction in a salt-free suspension is found to be quite different from that in a suspension containing added electrolyte.
Topics: Electric Conductivity; Electrolytes; Electrophoresis; Ions; Particle Size; Suspensions
PubMed: 34319604
DOI: 10.1002/elps.202100181 -
Expert Opinion on Drug Delivery Apr 2019Formulation of nanocrystals is one of the most important drug delivery systems for poorly soluble drug molecules. Nanocrystals are produced by techniques like... (Review)
Review
INTRODUCTION
Formulation of nanocrystals is one of the most important drug delivery systems for poorly soluble drug molecules. Nanocrystals are produced by techniques like precipitation, media milling, high-pressure homogenization, and so on. In order to achieve sustained release and higher absorption of nanosuspensions, intramuscularly administered nanosuspensions have been developed. As well, intramuscularly administered nanosuspensions have been implemented in order to improve the bioavailability of drug nanocrystals which have both a low oral bioavailability and cannot be administered by intravenous injection routes.
AREAS COVERED
This review summarizes studies that have focused on the production, classification, in vitro release and in vivo pharmacokinetics of intramuscularly administered nanosuspensions. In order to avoid common drawbacks of intramuscularly administered nanosuspensions, such as tissue residues and some local tissue damage, nanosuspensions with a reduced administration volume of high drug loading and extended therapeutic effects are developed.
EXPERT OPINION
Intramuscularly administered nano/micro crystal suspensions have been developed for the treatment of various diseases such as schizophrenia, hormone disordered diseases, HIV and more. Additionally, intramuscularly administered nanosuspensions are also a good route for the development of traditional chinese medicines which have lower oral bioavailability and are not suitable for intravenous injection.
Topics: Animals; Biological Availability; Drug Delivery Systems; Humans; Nanoparticles; Particle Size; Solubility; Suspensions
PubMed: 30827123
DOI: 10.1080/17425247.2019.1588248 -
Molecular Pharmaceutics May 2022Administration of highly concentrated monoclonal antibodies (mAbs) through injection is often not possible as the viscosity can be readily above 50 mPa·s when the...
Administration of highly concentrated monoclonal antibodies (mAbs) through injection is often not possible as the viscosity can be readily above 50 mPa·s when the concentration exceeds 150 mg/mL. Besides, highly concentrated mAb solutions always exhibit increased aggregation propensity and lower stability, which raise the difficulty for the successful development of highly concentrated mAb formulations. We hereby explored the possibility of suspension as another formulation form for high-concentration proteins to reduce viscosity and maintain stability. Specifically, we demonstrated that spray drying can serve as a process to prepare particles for suspension. Particles prepared from formulations with different mAb/trehalose mass ratios displayed good physical stability and antibody binding affinity, as indicated by circular dichroism, fluorescence spectroscopy, and surface plasmon resonance (SPR)-based bioassay analyses. During spray drying, a surface tension-dominated enrichment of mAb on the particle surface was observed, but this did not show a significant negative impact on mAb stability. Spray-dried particles were subsequently suspended into benzyl benzoate, and the resulting suspension showed good stability and a lower viscosity when compared to its counterpart solution. Furthermore, mAbs recovered from the suspension maintained their conformational structure. Our study demonstrated that the suspension displayed low viscosity and good physical stability, so it may offer novel opportunities for the preparation of highly concentrated protein formulations.
Topics: Antibodies, Monoclonal; Injections, Subcutaneous; Powders; Spray Drying; Suspensions; Viscosity
PubMed: 35417176
DOI: 10.1021/acs.molpharmaceut.2c00039 -
Soft Matter Jul 2021Viscous environments are ubiquitous in nature and in engineering applications, from mucus in lungs to oil recovery strategies in the earth's subsurface - and in all...
Viscous environments are ubiquitous in nature and in engineering applications, from mucus in lungs to oil recovery strategies in the earth's subsurface - and in all these environments, bacteria also thrive. The behavior of bacteria in viscous environments has been investigated for a single bacterium, but not for active suspensions. Dense populations of pusher-type bacteria are known to create superfluidic regimes where the effective viscosity of the entire suspension is reduced through collective motion, and the main purpose of this study is to investigate how a viscous environment will affect this behavior. Using a Couette rheometer, we measure shear stress as a function of the applied shear rate to define the effective viscosity of suspensions of Escherichia coli (E. coli), while varying both the bacterial density within the suspension and the viscosity of the suspending fluid. We document the remarkable observation that E. coli decreases the effective suspension viscosity to near-zero (superfluidic regime) for all solvent viscosities tested (1-17 mPa s). Specifically, we observe that the bacterial density needed to trigger this superfluidic regime and the maximum shear rate under which this regime can be sustained both decrease with increasing solvent viscosity. We find that the resulting rheograms can be well approximated by the Carreau-Yasuda law. Using this, we propose a constitutive model as a function of the solvent viscosity and the bacterial concentration only. This model captures the onset of the superfluidic regime and offers promising avenues for the modelling of flow of bacterial suspensions in viscous environments.
Topics: Bacteria; Escherichia coli; Rheology; Suspensions; Viscosity
PubMed: 34240724
DOI: 10.1039/d1sm00243k -
Current Drug Delivery 2021A ceftiofur hydrochloride long-acting oily suspension with no irritation was prepared by testing and optimizing the types and amounts of organic solvents, suspending...
OBJECTIVE
A ceftiofur hydrochloride long-acting oily suspension with no irritation was prepared by testing and optimizing the types and amounts of organic solvents, suspending agents, and surfactants.
METHODS
Its properties, stability, injection site irritation, release, and pharmacokinetics in pigs were evaluated. The optimum formulation was used ethyl oleate, aluminum monosterate, and span-80 as organic solvents, suspending agents, and surfactant, respectively. The drug microparticles were uniform long strip with size of 1.53 ± 0.11 μm and no agglomerations, and were evenly dispersed. The re-dispersed time, sedimentation rate and pH value of the suspension were 4 s under a magnetic shaker rotating at 20 r/min, 1 and 5.0, respectively. It could go through 7-gage needle smoothly with withdrawal volume of 9.9 mL/min.
RESULTS
The suspension showed good stability when stored away from light, no irritation at the injection site and sustained release in PBS buffer. After intramuscular administration, the drug concentration above 0.15 μg/mL was last for 120 h. Its elimination half-life (T), mean residence time (MRT), and bioavailability were increased by 1.73, 1.62, and 2.16 times compared to Excenel.
CONCLUSION
The results suggested that the suspension had excellent sustained-release and will make ceftiofur hydrochloride more effective and convenient to use.
Topics: Animals; Anti-Bacterial Agents; Biological Availability; Cephalosporins; Injections, Intramuscular; Suspensions; Swine
PubMed: 32885750
DOI: 10.2174/1567201817666200903165119 -
Skinmed 2021Vitiligo, a disorder of depigmentation, has a profound psychosocial burden. Surgical techniques using transplantation of tissue grafts or melanocytes have long been used... (Review)
Review
Vitiligo, a disorder of depigmentation, has a profound psychosocial burden. Surgical techniques using transplantation of tissue grafts or melanocytes have long been used to correct vitiliginous macules, often utilizing noncultured epidermal suspension. This procedure has undergone a remarkable transformation from its original methods in terms of preparation of recipient site, concentration and separation of melanocytes, incubation, and cryofreezing.Vitiligo is an acquired hypomelanotic disorder characterized by depigmented and circumscribed macules or patches, with loss of melanin and functional melanocytes from the epidermis. There is a broad range of therapeutic options for vitiligo, including topical agents, ultraviolet therapy, oral therapy, and surgical modalities. Transplanting autologous melanocytes from a normally pigmented donor area to the depigmented skin forms a common principle in all surgical techniques-be it grafting at tissue level or cellular level.Surgical modalities are further divided into tissue grafts and cellular grafts. Tissue grafting includes thin dermoepidermal grafts, punch grafts with full thickness, suction blister grafts, and epidermal harvesting systems. Cellular grafting employs noncultured epidermal suspensions and cultured melanocyte suspensions. The advantages of cellular grafting include large areas of depigmentation that can be treated with ease. In noncultured epidermal cell suspensions (NCES), keratinocytes are not separated from melanocytes, and they help to furnish factors that sustain and promote growth of melanocytes and homogeneity of repigmentation. A minimum density of melanocytes required for satisfactory repigmentation is 210-250 per mm..
Topics: Epidermis; Humans; Melanocytes; Suspensions; Transplantation, Autologous; Treatment Outcome; Vitiligo
PubMed: 35022112
DOI: No ID Found -
Journal of Ocular Pharmacology and... Dec 2019Cataract surgery is the most commonly performed surgical procedure worldwide. Despite the availability of new technologies and enhanced surgical techniques,... (Review)
Review
Cataract surgery is the most commonly performed surgical procedure worldwide. Despite the availability of new technologies and enhanced surgical techniques, inflammation-related complications after even uneventful cataract procedures remain the most common cause of poor visual outcomes. In this review article, we discuss the recent development of an intraocular steroid-based suspension and its use in cataract surgery. A PubMed literature search was conducted through December 2018 using the terms "cataract surgery," "dexamethasone," "inflammation," "treatment," and "prevention." The search was supplemented with the results of clinical trials registered at ClinicalTrials.gov; outcomes from both experimental and clinical research were included. Because dexamethasone interferes at multiple steps of the inflammatory cascade, this application seems to be an interesting option in the prevention of postsurgical inflammation. A single drug deposit into the anterior chamber might be an attractive alternative to frequent drop installations. In addition, dexamethasone intravitreal inserts are an option in high-risk individuals-in particular, in those with preexistent macula edema. Nevertheless, a careful evaluation of the agents is required, because the present state of knowledge is based on only a few registered trials. Control of postoperative inflammation is one of the key factors in achieving satisfactory outcomes in cataract surgery. As the introduction of intracameral antibiotics has brought benefits to cataract surgery, dexamethasone intraocular suspension for anterior chamber steroid placement might assist in improving surgical outcomes. This could particularly refer to patients with a higher risk of postsurgical inflammation, especially in eyes with diabetic retinopathy or uveitis.
Topics: Cataract Extraction; Dexamethasone; Diabetic Retinopathy; Humans; Inflammation; Injections, Intraocular; Suspensions; Time Factors; Uveitis
PubMed: 31644364
DOI: 10.1089/jop.2019.0072 -
Medical Principles and Practice :... 2021The objectives were to prepare, characterize, and evaluate different ibuprofen (IBU) nanosuspensions.
INTRODUCTION
The objectives were to prepare, characterize, and evaluate different ibuprofen (IBU) nanosuspensions.
METHODS
The nanosuspensions produced by ultrahomogenization were compared with a marketed IBU suspension for particle size, in vitro dissolution, and in vivo absorption. Five groups of rabbits were orally administered with 25 mg/kg of IBU nanosuspension, nanoparticles, unhomogenized suspension, marketed product, and untreated suspension. A sixth group received 5 mg/kg IBU intravenously. Blood samples obtained were analyzed by chromatography.
RESULTS
The nanosuspensions showed significant decrease in particle size. Polyvinylpyrrolidone (PP) K30 profoundly increased aqueous solubility of IBU. Addition of Tween 80 (TW), in equal amount as PP (IBU:PP:TW, 1:2:2 w/w), resulted in much smaller particle size and better dissolution rate. The Cmax values achieved were 14.8 ± 1.64, 11.1 ± 1.37, 9.01 ± 0.761, 7.03 ± 1.38, and 3.23 ± 1.03 μg/mL, and the tmax values were 36 ± 8.2, 39 ± 8.2, 100 ± 17.3, 112 ± 15, and 105 ± 17 min for the nanosuspension, nanoparticle, unhomogenized suspension, marketed IBU suspension, and untreated IBU suspension in water, respectively. Bioavailability of the different formulations relative to the marketed suspension was found to be in the following sequence: nanosuspension > unhomogenized suspension > nanoparticles > untreated IBU suspension.
CONCLUSION
IBU/PP/TW nanosuspension showed enhanced in vitro and in vivo performance as compared to the marketed product. Nanosuspensions prepared by the ultrahigh-pressure homogenization technique can be used as a good formulation strategy to enhance the rate and extent of absorption of poorly soluble drugs.
Topics: Animals; Biological Availability; Chromatography, High Pressure Liquid; Ibuprofen; Nanostructures; Nanotechnology; Rabbits; Solubility; Solvents; Suspensions
PubMed: 33823524
DOI: 10.1159/000516299 -
Journal of the Royal Society, Interface Jan 2022Suspension feeders (SFs) evolved a high diversity of mechanisms, sometimes with remarkably convergent morphologies, to retain plankton, detritus and man-made particles...
Suspension feeders (SFs) evolved a high diversity of mechanisms, sometimes with remarkably convergent morphologies, to retain plankton, detritus and man-made particles with particle sizes ranging from less than 1 µm to several centimetres. Based on an extensive literature review, also including the physical and technical principles of solid-liquid separation, we developed a set of 18 ecological and technical parameters to review 35 taxa of suspension-feeding Metazoa covering the diversity of morphological and functional principles. This includes passive SFs, such as gorgonians or crinoids that use the ambient flow to encounter particles, and sponges, bivalves or baleen whales, which actively create a feeding current. Separation media can be flat or funnel-shaped, built externally such as the filter houses in larvaceans, or internally, like the pleated gills in bivalves. Most SFs feed in the intermediate flow region of Reynolds number 1-50 and have cleaning mechanisms that allow for continuous feeding. Comparison of structure-function patterns in SFs to current filtration technologies highlights potential solutions to common technical design challenges, such as mucus nets which increase particle adhesion in ascidians, vanes which reduce pressure losses in whale sharks and changing mesh sizes in the flamingo beak which allow quick adaptation to particle sizes.
Topics: Animals; Biomimetics; Feeding Behavior; Plankton; Sharks; Suspensions
PubMed: 35078340
DOI: 10.1098/rsif.2021.0741 -
European Journal of Pharmaceutics and... Mar 2022Rapid precorneal loss of topically applied eye drops limits ocular drug absorption. Controlling release and precorneal residence properties of topical formulations may...
Rapid precorneal loss of topically applied eye drops limits ocular drug absorption. Controlling release and precorneal residence properties of topical formulations may improve ocular drug bioavailability and duration of action. In this study, we evaluated in vivo ocular pharmacokinetics of dexamethasone in rabbits after application of a drug solution (0.01%), suspension (Maxidex® 0.1%), and hydrogels of 2-hydroxyethyl methacrylate (HEMA) and acrylic acid (AAc) copolymers. The rabbits received a single eyedrop (solution or suspension) or dexamethasone-loaded hydrogel topically. Dexamethasone in tear fluid was sampled with glass capillaries and quantitated by LC-MS/MS. Higher dexamethasone exposure (AUC) in the tear fluid was observed with the suspension (≈3.6-fold) and hydrogel (12.8-fold) as compared to the solution. During initial 15 min post-application, the highest AUC of dissolved dexamethasone was seen after hydrogel application (368 min*µg/mL) followed by suspension (109.9 min*µg/mL) and solution (28.7 min*µg/mL. Based on kinetic simulations, dexamethasone release from hydrogels in vivo and in vitro is comparable. Our data indicate that prolonged exposure of absorbable dexamethasone in tear fluid is reached with hydrogels and suspensions. Pharmacokinetic understanding of formulation behavior in the lacrimal fluid helps in the design of dexamethasone delivery systems with improved ocular absorption and prolonged duration of action.
Topics: Animals; Chromatography, Liquid; Dexamethasone; Drug Liberation; Hydrogels; Kinetics; Rabbits; Suspensions; Tandem Mass Spectrometry
PubMed: 35121080
DOI: 10.1016/j.ejpb.2022.01.005