Mechanistic understanding of salt-induced drug encapsulation in nanosuspension via acid-base neutralization as a nanonization platform technology to enhance dissolution rate of pH-dependent poorly water-soluble drugs.

An acid-base neutralization technique has generated interest for the ability to achieve an enhanced dissolution of pH-dependent weakly basic or acidic poorly water-soluble drugs. However, the underlying nanonization mechanism, following acid-base neutralization, requires further elucidation. We hypothesized that the nanosuspensions (NSPs) via nanonization of drug particles could be attributed to the "salt-induced effect" and surfactant-driven micellization after acid-base neutralization. Rebamipide (RBM) and valsartan (VAL) were chosen as model drugs owing to poor water solubility and pH-dependent aqueous solubility. The drug NSP was rapidly obtained via salt formation (NaCl) after neutralization of the drug in basic NaOH solution and poloxamer 407 (POX 407) in acidic HCl solution. The NSP surrounded by NaCl salt was further stabilized by POX 407. The resulting NaCl salt modulated the critical micelle aggregation of POX 407, stabilizing the drug-loaded NSP in a cage of salt and micellar surfactant. In non-assisted homogenization, size analysis indicated the relationship between salt concentration and size reduction. Fourier transform infrared (FTIR) spectra revealed that the existence of hydrogen bonding between the drug and surfactant after neutralization, attributed to NSP size reduction. Changes in drug crystallinity to the nano-amorphous state were confirmed by powder X-ray diffraction (PXRD). Overall, the salt-induced drug NSP synergistically enhanced the dissolution rate, narrowing a gap between drug dissolution profiles in different pH environments.

Development and characterization of novel ambroxol sustained-release oral suspensions based on drug-polymeric complexation and polymeric raft formation.

The aim was to develop sustained-release aqueous suspensions of ambroxol utilizing drug-polymer complexation and raft-forming formulations. Ambroxol-carrageenan (ABX-CRG) complexation was studied for the optimum binding capacity, which was used to prepare the complex by kneading and coprecipitation. The prepared complex was characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry and powder X-ray diffractometry. The complex was formulated as suspensions in aqueous raft-forming vehicle of sodium alginate (NA) and calcium carbonate (CC). The suspensions differed in the molecular weight and concentration of NA, in addition to CC level and inclusion of CRG in excess of drug-polymer complexation. In 0.1 M HCl as simulated gastric fluid, the suspensions were observed for their ability to form rafts and studied for drug-release. The optimum sustained-release, raft forming and pourable formulation using high molecular weight NA, NA concentration of 18 mg/ml and CC concentration of 9 mg/ml was reached. Another optimum suspension was obtained by replacement of CC with excess CRG. However, pH dissolution profiles of the optimum suspensions revealed less pH sensitivity of the release consequent to this replacement as well as more stable ABX release upon aging. Relative to Gaviscon liquid, the optimum suspensions formed rafts of similar strength and higher resilience.

Preparation, Characterization and In Vivo Assessment of Repaglinide Nanosuspension for Oral Bioavailability Improvement.

AIMS AND BACKGROUND: The objective of the study was to improve the bioavailability of poorly soluble repaglinide (RPG) by preparing nanosuspension with poloxamer 188 using high pressure homogenization (HPH). The recent patents on nanocrystals (US20150337006A1) facilitated selection of drug and polymer. METHODS: Suspensions containing dissimilar sized particles were prepared by ultrasonication and HPH. The prepared aqueous suspensions were lyophilized and then characterized. Further, the dried aqueous suspensions were evaluated for drug content, solubility, in vitro dissolution, oral bioavailability study and stability study. RESULTS: RPG nanoparticles size, polydispersity index (PDI) and zeta potential were found to be 280.8 ± 15 nm, 0.279 ± 0.04 and - 25.81 ± 1.6mV, respectively. DSC and XRD results showed that RPG particles in aqueous suspensions were present in a crystalline state; however, RPG nanoparticles exhibited decreased lattice energy due to smaller particle size. Nanoparticles prepared by HPH exhibited significant improvements in solubility and dissolution rate. Oral bioavailability was found to be enhanced by 1.93 fold in comparison with that of plain RPG. The nanosuspension was found to be stable when stored at 5°C ± 3°C. CONCLUSION: The outcomes of the study revealed significant enhancement in dissolution rate and oral bioavailability of RPG due to size reduction to nano range by HPH.

In-air microfluidics enables rapid fabrication of emulsions, suspensions, and 3D modular (bio)materials.

Microfluidic chips provide unparalleled control over droplets and jets, which have advanced all natural sciences. However, microfluidic applications could be vastly expanded by increasing the per-channel throughput and directly exploiting the output of chips for rapid additive manufacturing. We unlock these features with in-air microfluidics, a new chip-free platform to manipulate microscale liquid streams in the air. By controlling the composition and in-air impact of liquid microjets by surface tension-driven encapsulation, we fabricate monodisperse emulsions, particles, and fibers with diameters of 20 to 300 µm at rates that are 10 to 100 times higher than chip-based droplet microfluidics. Furthermore, in-air microfluidics uniquely enables module-based production of three-dimensional (3D) multiscale (bio)materials in one step because droplets are partially solidified in-flight and can immediately be printed onto a substrate. In-air microfluidics is cytocompatible, as demonstrated by additive manufacturing of 3D modular constructs with tailored microenvironments for multiple cell types. Its in-line control, high throughput and resolution, and cytocompatibility make in-air microfluidics a versatile platform technology for science, industry, and health care.

Mechanochemical Synthesis of Pharmaceutical Cocrystal Suspensions via Hot Melt Extrusion: Feasibility Studies and Physicochemical Characterization.

Engineered cocrystals offer an alternative solid drug form with tailored physicochemical properties. Interestingly, although cocrystals provide many new possibilities, they also present new challenges, particularly in regard to their design and large-scale manufacture. Current literature has primarily focused on the preparation and characterization of novel cocrystals typically containing only the drug and coformer, leaving the subsequent formulation less explored. In this paper we propose, for the first time, the use of hot melt extrusion for the mechanochemical synthesis of pharmaceutical cocrystals in the presence of a meltable binder. In this approach, we examine excipients that are amenable to hot melt extrusion, forming a suspension of cocrystal particulates embedded in a pharmaceutical matrix. Using ibuprofen and isonicotinamide as a model cocrystal reagent pair, formulations extruded with a small molecular matrix carrier (xylitol) were examined to be intimate mixtures wherein the newly formed cocrystal particulates were physically suspended in a matrix. With respect to formulations extruded using polymeric carriers (Soluplus and Eudragit EPO, respectively), however, there was no evidence within PXRD patterns of either crystalline ibuprofen or the cocrystal. Importantly, it was established in this study that an appropriate carrier for a cocrystal reagent pair during HME processing should satisfy certain criteria including limited interaction with parent reagents and cocrystal product, processing temperature sufficiently lower than the onset of cocrystal Tm, low melt viscosity, and rapid solidification upon cooling.

Emerging Potential of Nanosuspension-Enabled Drug Delivery: An Overview.

Poor aqueous solubility is one of the key concerns of the majority of new drug molecules. One of the important problems associated with such drugs is that they often lead to low bioavailability. Researchers have used various techniques, but little success has been achieved due to poor stability and industrial viability, including technique cost. Of the numerous techniques, nanosuspensions (NSs) have drawn interest in improving solubility. NSs are dispersions of nanosized drug particles stabilized with the aid of appropriate agents. Stabilizers for NSs are generally recognized as safe (GRAS) excipients that can be chosen from a number of surfactants and/or polymers to food proteins. The commonly used techniques for preparation of NSs including top-down and bottom-up methods, along with new fabrication techniques based on supercritical (SC) fluids, are reviewed. This review also includes preparatory techniques, characterization, potential applications, and recent advancements in the field of NSs.

Recent survey on nanosuspension: a patent overview.

The major goals of designing nanosuspension of nanosize materials are increasing due to their tremendous potential as a drug delivery system with the wide range of applications. Nanosuspension is a unique tool for improving the bioavailability of poorly soluble drugs. Nanosuspension drug delivery has wide range of application like oral, injectable, transdermal, inhalation, peroral, ocular, pulmonary and topical etc. by improviing the bioavailability, reducing the dose, gastric irritation, decreasing intra subject variability and increasing adhesivness with intestinal membrane. Recently, nanosuspension has been received much interest as a way to resolve solubility and stability problem because of their cost-effectiveness and technical simplicity compare to other liposome and colloidal drug carriers. Nanosuspensions are engaged to control particle size, surface properties and release of pharmacologically active agents in order to achieve the site-specific action of the drug at the therapeutically optimal rate, improve the bioavaibility of drug with poor solubility and dose regimen. Application and preparation method of nanosuspension has been reported by research articles and patented in different countries. Most of the marketed nanosuspensions are in preclinical and clinical based study for its application. More than 100 patents have been published on nanosuspensions by the recent days. This patent reviews covers different methods of pharmaceutical preparation and applications in drug delivery as well as the recent marketed published or granted patent surveys. This patent review is useful in enhance the knowledge of controlled drug delivery and applications.

Structure and dynamics studies of concentrated micrometer-sized colloidal suspensions.

We present an experimental study of the structural and dynamical properties of concentrated suspensions of different sized polystyrene microspheres dispersed in glycerol for volume fraction concentrations between 10% and 20%. The static structure, probed with ultrasmall-angle X-ray scattering, shows a behavior very similar to that of hard spheres. The equilibrium dynamics is probed with ultrasmall-angle X-ray scattering-X-ray photon correlation spectroscopy, a new technique that overcomes the limits of visible light-scattering techniques imposed by multiple scattering and is suitable for studies of optically opaque materials containing micrometer-sized structures. We found that the intensity autocorrelation functions are better described by a stretched exponential function and microspheres in a concentrated suspension move collectively. We also found that the inverse of the effective diffusion coefficients displays a peak with respect to the scattering vector that resembles the peaks in the static structure factors, which indicates that a long-lived, low free-energy state exists. The relaxation time is approximately inversely related to scattering vector, a behavior consistent with models that describe the dynamics in terms of random, local structural arrangements in disordered media.

In vivo evaluation of silybin nanosuspensions targeting liver.

The present study investigated the production, in vivo biodistribution and hepatoprotective of two formulated silybin nanosuspensions with different particle size. The physicochemical properties of the two formulated silybin nanosuspensions were investigated by TEM, AFM and SEM. A kinetic study was conducted to evaluate the influence of particle size on the in vivo tissue distribution following intravenous administration in the mice. The in vivo hepatoprotective studies were conducted on beagle dogs with optimized setting. A clear physicochemical difference was observed among the silybin solution, larger particles and the small particles. The formulation of larger particle size was preferentially targeted at liver and spleen. The silybin nanosuspensions, administrated either intravenously or orally, presented significant (P < or = 0.05) hepatoprotective effect by reducing the serum marker enzymes such as AST, ALT, ALP, TBIL and GGT. Histopathological study further confirmed the hepatoprotective activity of the two silybin nanosuspensions formulations when compared with the CCl4 treated control group. These results indicate that the nanosuspensions approaches could be used to improve the drug target delivery and therapeutic efficacy of the silybin.

Targeted delivery of a poorly water-soluble compound to hair follicles using polymeric nanoparticle suspensions.

This study explored the utility of topically applied polymeric nanoparticle suspensions to target delivery of poorly water-soluble drugs to hair follicles. Several formulations of amorphous drug/polymer nanoparticles were prepared from ethyl cellulose and UK-157,147 (systematic name (3S,4R)-[6-(3-hydroxyphenyl)sulfonyl]-2,2,3-trimethyl-4-(2-methyl-3-oxo-2,3-dihydropyridazin-6-yloxy)-3-chromanol), a potassium channel opener, using sodium glycocholate (NaGC) as a surface stabilizer. Nanoparticle suspensions were evaluated to determine if targeted drug delivery to sebaceous glands and hair follicles could be achieved. In in vitro testing with rabbit ear tissue, delivery of UK-157,147 to the follicles was demonstrated with limited distribution to the surrounding dermis. Delivery to hair follicles was also demonstrated in vivo, based on stimulation of hair growth in tests of 100-nm nanoparticles with a C3H mouse model. The nanoparticles were well-tolerated, with no visible skin irritation. In vivo tests of smaller nanoparticles with a hamster ear model also indicated targeted delivery to sebaceous glands. The nanoparticles released drug rapidly in in vitro nonsink dissolution tests and were stable in suspension for 3 months. The present results show selective drug delivery to the follicle by follicular transport of nanoparticles and rapid release of a poorly water-soluble drug. Thus, nanoparticles represent a promising approach for targeted topical delivery of low-solubility compounds to hair follicles.

Solid lipid nanoparticles suspension versus commercial solutions for dermal delivery of minoxidil.

Solid lipid nanoparticles have been reported as possible carrier for skin drug delivery. Solid lipid nanoparticles are produced from biocompatible and biodegradable lipids. Solid lipid nanoparticles made of semi-synthetic triglycerides stabilized with a mixture of polysorbate and sorbitan oleate were loaded with 5% of minoxidil. The prepared systems were characterized for particle size, pH and drug content. Ex vivo skin penetration studies were performed using Franz-type glass diffusion cells and pig ear skin. Ex vivo skin corrosion studies were realized with a method derived from the Corrositex(®) test. Solid lipid nanoparticles suspensions were compared to commercial solutions in terms of skin penetration and skin corrosion. Solid lipid nanoparticles suspensions have been shown as efficient as commercial solutions for skin penetration; and were non-corrosive while commercial solutions presented a corrosive potential. Solid lipid nanoparticles suspensions would constitute a promising formulation for hair loss treatment.

Preparation and evaluation of a self-emulsifying drug delivery system of etoposide-phospholipid complex.

AIM: The aim of this study was to develop a new phospholipid complex self-emulsifying drug delivery system (PC-SEDDS) to enhance bioavailability of oral etoposide, a drug with poor water solubility. METHODS: Etoposide-phospholipid complex (EPC) was prepared by reacting etoposide and phospholipid in tetrahydrofuran and confirmed as a phospholipid compound by differential scanning calorimetry (DSC). Solubility of EPC and etoposide was determined in various vehicles. Pseudoternary phase diagrams were constructed to identify the efficient self-emulsification region of EPC-SEDDS, and the effects of oil concentration, drug loading, and aqueous media on droplet size were investigated. RESULTS: The optimal formulation of EPC-SEDDS was EPC:octyl and decyl monoglyceride (ODO):Cremopher EL:PEG-400 (1:20:48:32) (w/w/w/w). Compared with etoposide-phospholipid complex suspension (EPCS) and etoposide suspension (ES), cumulative release of etoposide from EPC-SEDDS increased by 1.31 and 2.65 fold at 24 hours, respectively. Compared with ES, relative bioavailability of EPC-SEDDS, E-SEDDS, and EPCS after oral administration in rats was enhanced by 60.21-, 44.9-, and 8.44- fold, respectively. CONCLUSIONS: The synergistic effect between PC and SEDDS contributed to the enhanced bioavailability of etoposide. It was concluded that PC-SEDDS proved to be a potential system for delivering orally administered hydrophobic compounds including etoposide.

Facile synthesis for colloid silica cross-linked threadlike micelles based on block copolymer self-assembly.

A new class of silica cross-linked threadlike micelles has been successfully synthesized in the form of stable colloidal suspensions by using block copolymer P123 (EO(20)PO(70)EO(20)) as template, tetramethyl orthosilicate as silica source, and 3-aminopropyltriethoxysilane as stabilizing agent. The aggregation of threadlike hybrid micelles is suppressed by electrostatic repulsion from the positive -NH(3)(+) on the surfaces of threadlike hybrid micelles in strong acidic media. Compared with P123 micelles, the threadlike hybrid micelles have significantly improved stability against dilution. Furthermore, the threadlike hybrid micelles are potential drug carrier and have a higher loading capacity and a slower release rate.

Nanosuspensions: a promising formulation for the new phospholipase A2 inhibitor PX-18.

PX-18 is a new highly potent phospholipase A(2) inhibitor with a poor aqueous solubility. Therefore, it was formulated as nanosuspensions with an active content of 1% (w/w), 5% (w/w) and 10% (w/w) using high-pressure homogenization. By contact angle measurements on compressed discs of PX-18, Tween 80 was identified as best wetting agent of PX-18 and therefore used to stabilize the nanosuspensions. The achieved particle size of all nanosuspensions was well in the nanometer range. For the 1% (w/w) PX-18 nanosuspension an average particle size below 50 nm was measured by photon correlation spectroscopy (PCS). A good reproducibility of the mean particle size was found in between different batches. As postulated by the zeta potential of the nanosuspensions, a good physical stability over an observation period of 180 days was obtained when stored at 5+/-3 degrees C. PX-18 formulated as nanosuspensions was chemically stabile. An increase in saturation solubility was found after formulating PX-18 as nanosuspension compared to bulk material, favourable for increasing bioavailability.

An assessment of beclomethasone dipropionate clathrate formation in a model suspension metered dose inhaler.

The aims of this study were to investigate and characterize the physico-chemical properties of beclomethasone dipropionate (BDP) crystallized from tricholoromonofluoromethane (CFC-11). Physical interactions in a model pressurised metered dose inhaler (pMDI) system and changes in surface energy after size reduction (micronization) were determined. Although CFC-11 has largely been phased out of use in pMDIs due to its ozone depletion potential, the BDP CFC-11 clathrate is a stable entity and thus suitable as a model for our initial investigations. In addition, although propellant clathrates have been known for sometime, as far as the authors are aware, their surface energies and adhesive interactions have not been reported. The structure of the clathrate was investigated using scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and X-ray powder diffraction (X-RPD). In addition, atomic force microscopy (AFM) was employed to determine the dispersive surface free energy (SE) and force of adhesion (F(adh)) of the BDP CFC-11 clathrate with different pMDI components in a model propellant (decafluoropentane). The dispersive surface free energies for anhydrous BDP (micronized), the CFC-11 clathrate and ball-milled BDP CFC-11 clathrate are (47.5+/-4.9) mJ m(-2), (11.3+/-4.1) mJ m(-2) and (15.2+/-1.3) mJ m(-2) respectively. Force of adhesion results shows that BDP CFC-11 clathrates, even after being ball-milled for 2.5h, have a lower F(adh) compared to micronized anhydrous BDP with different pMDI components. This shows that the formation of the crystalline CFC-11 clathrate is advantageous when compared to the micronized anhydrous form, in terms of its surface energy and potential interactions within a suspension MDI formulation. In the wider context, this work has implications for the future development of HFA formulations with APIs which are prone to the formation of propellant clathrates.

The topical delivery of benzoyl peroxide using elegant dynamic hydrofluoroalkane foams.

Formulating benzoyl peroxide (BPO) in an effective topical product is challenging due to its poor water solubility and chemical instability, but delivering BPO using elegant foams is an attractive solution to this problem. The aim of this work was to investigate how nanoparticle properties influence BPO release and permeation when administrated using dynamic hydrofluoroalkane foams. Lipid (LN, approximately 50 nm) and polymeric (PN, approximately 350 nm) nanoparticles were produced and loaded into topical foams. Drug release and permeation was measured using ultrafiltration and Franz cells studies, respectively. No BPO release was detected when the nanoparticles were stored in the aqueous solvent, but upon administration to silicone membrane the pluronic surfactant-induced LN swelling and BPO delivery (35.7 +/- 3.8 microg cm(-2) h(-1)). In the same situation the PN aggregated with a delivery rate of 2.5 +/- 0.2 microg cm(-2) h(-1). Surprisingly the aqueous nanosuspensions delivered BPO at an equivalent rate to the foams despite the poor drug solubility in the dispersing medium presumably due to ultra-rapid BPO solubilization kinetics of the drug in water. The delivery of BPO from the foams (0.1% BPO) was superior compared to the commercial products (5% BPO), but further testing in human skin is required prior to clinical use.

A comparative study of top-down and bottom-up approaches for the preparation of micro/nanosuspensions.

Nano-sizing offers a promising method for the formulation of poorly aqueous soluble compounds. Nanosuspensions can be prepared by top-down or bottom-up approaches. The different conditions encountered in these two approaches can greatly affect nanosuspension characteristics. In this study, milling via microfluidization and precipitation via sonication were compared to study their effects on the formation and stability of ibuprofen nanosuspensions. Various stabilizers (SLS, PVP K-30, Pluronic F-68 and F-127, Tween 80 and different hydroxypropyl methylcelluloses (HPMCs)) were evaluated. Both processes resulted in a similar trend in the initial particle size and comparable short-term physical stability of suspensions. Of all the stabilizers investigated, the HPMCs were the most effective both in terms of particle size reduction and short-term physical stability. Differences in stabilizer efficacy were observed between the two processing methods. The initial particle size of the suspensions prepared using microfluidization correlated with the solubility of ibuprofen in the respective stabilizer solutions. Whereas, the initial particle size of suspensions prepared using precipitation under sonication correlated with the HLB values of the stabilizers. The solubility of ibuprofen in the stabilizer solution also played a significant role in the increase in particle size on storage, indicating Ostwald ripening.

Freeze-dried nifedipine-lipid nanoparticles with long-term nano-dispersion stability after reconstitution.

Nifedipine (NI) is a poorly water-soluble drug and its oral bioavailability is very low. To improve the water solubility, NI-lipid nanoparticle suspensions were prepared by a combination of co-grinding by a roll mill and high-pressure homogenization without any organic solvent. The mean particle size and zeta potential of the NI-lipid nanoparticle suspensions were about 52.6 nm and -61.8 mV, respectively, and each parameter remained extremely constant during a period of 4 months under 6 degrees C and dark conditions, suggesting that the negative charge of the phospholipid, dipalmitoyl phosphatidylglycerol, is very effective in preventing coagulation of the particles. In order to assure the nano-order particle size of the suspensions in view of long-term stability, a freeze-drying technique was applied to the NI-lipid nanoparticle suspensions. The mean particle size of freeze-dried NI-lipid nanoparticles after reconstitution was significantly increased in comparison to that of the preparations before freeze-drying. It was found, however, that the addition of sugars (glucose, fructose, maltose or sucrose) to the suspensions before freeze-drying inhibited the aggregation of nanoparticles, suggesting that the long-term stability storage of freeze-dried NI-lipid nanoparticles after reconstitution would be overcome. In addition, freeze-dried nanoparticles with 100mg sugar (glucose, fructose, maltose or sucrose) showed excellent solubility (>80%), whereas without sugar, as a control, showed low solubility (<20%). It was found that negatively charged phospholipids and sugars prevent coagulation of NI nanoparticle suspensions, and reproduce the nanoparticle dispersion after reconstitution; and remarkably increase the apparent solubility of nifedipine.

Diclofenac nanosuspensions: influence of preparation procedure and crystal form on drug dissolution behaviour.

The aim of this paper was to ascertain the role of drug crystalline form and preparation procedure in nanosuspension formulations in order to optimise dissolution properties of lipophilic, poorly soluble drugs, thus improving their oral bioavailability. The non-steroidal anti-inflammatory drug diclofenac acid (DCF), which is known to exist in different crystal forms, was chosen as a model drug. To this purpose, the influence of homogenization technique was studied by preparing several nanosuspensions with two different crystalline forms of the drug (DCF1 and DCF2). Particle size and size distribution, morphology, microstructure, and thermal behaviour of the different formulations were studied by photon correlation spectroscopy (PCS), scanning electron microscopy (SEM), X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC). Solubility studies of the bulk drug crystalline forms and dissolution experiments of nanosuspensions in comparison with different controls (bulk drug, physical mixtures, coarse suspensions) were carried out in different media: distilled water, simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). Besides well known factors capable of affecting drug nanoparticle dissolution, results showed that drug dissolution rate in nanosuspensions is strongly affected by the drug solubility, which depends on the crystal form, and preparation procedure (high pressure homogenization process). Results demonstrated that this process partially transformed DCF2 in DCF1 while it did not have any effect on the DCF1 crystals.

Synthesis of colloidal aqueous suspensions of a layered gadolinium hydroxide: a potential MRI contrast agent.

A layered gadolinium hydroxychloride (LGdH), [Gd2(OH)5(H2O)x]Cl, was synthesized from an aqueous solution of GdCl3.6H2O. The X-ray diffraction (XRD) and the selected area electron diffraction (SAED) studies showed that this compound crystallizes in the orthorhombic structure (a = 12.88(4) A, b = 7.30(2) A, and c = 8.46(3) A) which is isostructural with [Eu2(OH)5(H2O)x]Cl. Interestingly, this layered material was readily dispersed and led to a stable colloidal nanosheet in aqueous medium. The obtained colloidal solutions were characterized by the evaluation of their stability in acidic solution, their in vitro cytotoxicity, and their magnetic resonance imaging (MRI) relaxation properties. It is reported that the relaxometry analysis of LGdH suspensions exhibits a sufficient contrast effect for T1 weighted magnetic resonance imaging.