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Functional properties of liposoluble vitamins have been extensively used in the food industry for the development of nutrition-based products. But their efficacy tends to decline because of oxidation reactions as they are highly sensitive to free radicals and other metallic ions. In addition, lipid-soluble vitamins also demonstrate limited water solubility. Thus, dissolution in aqueous-based foods is a challenge. Some techniques have been suggested for the protection of lipid-soluble vitamins. One such method is nanoencapsulation which has recently posed a novel platform for showing enhanced bioavailability, higher shelf life and controlled release of entrapped liposoluble vitamins. In this work, we focus on five model lipid-based nanodelivery systems: (1) conventional nanoemulsions, (2) nanoliposomes, (3) solid lipid nanoparticles, (4) nanostructured lipid carriers and (5) nanosuspensions. First, we focus on the specific liquid and electrochemical techniques available for the preparation of such nanostructures. In the next phase, the five different lipid-based nanostructures have been discussed with their formulation techniques (energy and pressure attributes) concerning their encapsulation strategy for lipid-soluble vitamins. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • AmB-HPH and AmB-AP improved the solubility and bioavailability of amphotericin B. • The solubility and dissolution of AmB-AP were superior to those of AmB-HPH. • AmB-HPH exhibited higher relative bioavailability than AmB-AP. Abstract Amphotericin B (AmB) is a widely used polyene antifungal agent; however, its poor solubility limits its clinical application. In this study, AmB nanosuspensions were prepared by a high pressure homogenization method (AmB-HPH) and an antisolvent precipitation method (AmB-AP) to improve the drug solubility. To reveal the distinct influences of these two different preparation methods, systematic comparisons of particle size, crystalline state, wettability, in vitro dissolution and in vivo pharmacokinetics on the properties of AmB-HPH and AmB-AP were performed. The results indicated that AmB-AP was in an amorphous state, exhibiting higher saturation solubility and dissolution rate than those of AmB-HPH in the crystalline state. However, the relative bioavailability of AmB-HPH was higher than that of AmB-AP in vivo , which was likely attributed to its better stability. In conclusion, both AmB-HPH and AmB-AP can enhance the solubility and bioavailability of AmB, but the stability of the nanosuspension prepared by the anti-solvent precipitation method should be carefully considered. [ABSTRACT FROM AUTHOR]

Annonaceous acetogenins (ACGs) are one of the most active constituents isolated from Annona species with potent antitumor activity. However, the poor solubility and severe side effect greatly limit their use in clinic. In this study, folic acid (FA) modified annonaceous acetogenins nanosuspensions (FA-PEG-ACGs-NSps) had been successfully prepared using DSPE-PEG-FA and soybean lecithin (SPC) as stabilizers. The resultant FA-PEG-ACGs-NSps had a mean particle size of 119.7 nm, a zeta potential of -23.0 mV and a high drug payload of 49.68%. The obtained ACGs-NSps had a good stability in various physiological media, and showed sustained drug release. Compared to common ACGs nanoparticles (PEG-ACGs-NSps), FA-PEG-ACGs-NSps showed significantly enhanced in vitro cytotoxicity against folate receptor-positive HeLa cell lines (IC50, 0.483 μg/mL vs. 0.915 μg/mL, p < .05), which could be effectively reversed simply by pretreatment of free FA. In vivo experiments demonstrated that FA-PEG-ACGs-NSps brought more drug molecules into tumors and greatly improved the antitumor efficacy (TIR, 76.45% vs. 25.29%, p < .001). Therefore, DSPE-PEG-FA is considered as a proper stabilizer with active targeting effect for ACGs-NSps to reduce toxicity, enlarge the safe dosage range and apply in clinic for the treatment of folate-positive tumors. Therefore, FA-PEG-ACGs-NSps may be a prospective drug delivery system for ACGs to improve their therapeutic window and find application in clinic to treat FR over-expressed tumors. [ABSTRACT FROM AUTHOR]

The aim of this study was to improve the oral bioavailability of a practically insoluble drug, efonidipine hydrochloride (EFH), by agglomeration in acid solution/gastric fluid. The EFH nanosuspension was prepared by the wet-milling method with F68 as a dispersing agent, SDS as an auxiliary stabilizer and l -arginine as a pH adjusting agent. The EFH nanosuspension have been prepared in industrial scale-up. The dissolution rate of the EFH nanosuspension was greater than that of bulk EFH. An in vitro intestinal permeability study showed a clear increase in the apparent permeability of different intestinal segments compared with bulk EFH. Also, a pharmacokinetic study showed that the C max and AUC 0-24h of the nanosuspensions were approximately 1.76-fold and 2.2-fold greater than that of bulk EFH, respectively, and there was no significant difference compared with commercial tablets. It appears that wet-milling offers an effective approach to improve the dissolution rate and oral absorption of this practically insoluble drug. [ABSTRACT FROM AUTHOR]

The present study aimed to prepare stable DL-tetrahydropalmatine (DL-THP) nanosuspensions of optimized formulation with PEGylated chitosan as a multifunctional stabilizer using the antisolvent precipitation method. A central composite design project of three factors and five-level full factorial (53) was applied to design the experimental program, and response surface methodology analysis was used to optimize the experimental conditions. The effects of critical influencing factors such as PEGylated chitosan concentration, operational temperature, and ultrasonic energy on particle size and zeta potential were investigated. Under the optimization nanosuspension formulation, the particle size was 269 nm and zeta potential was at 37.4 mV. Also, the DL-THP nanosuspensions maintained good physical stability after 2 months, indicating the potential ability of the multifunctional stabilizer for stable nanosuspension formulation. Hence, the present findings indicated that PEGylated chitosan could be used as the ideal stabilizer to form a physically stable nanosuspension formulation. [ABSTRACT FROM AUTHOR]

Polymeric composite nanofibers have been fabricated simply by the electrospinning of polymeric solutions containing a wide variety of suspended inclusions such as nanoparticles and nanotubes. The electrospinning process for fabrication of composite nanofibers is a multi-phase and multi-physics process. In this paper, a modified particle suspension model for electrospinning nanosuspensions is established to research the electrospinning process. The model can offer in-depth insight into physical understanding of the complex process which can not be fully explained experimentally. [ABSTRACT FROM AUTHOR]

Nanosuspensions technique is an important tool to enhance the saturation solubility and dissolution velocity of poorly soluble drugs. Trans-resveratrol (t-Res) with extensive pharmacological effects was severely restricted by poor solubility and short biological half-life. In this study, anti-solvent precipitation was employed to development trans-resveratrol nanosuspensions (t-Res NS) with PVPK30 as stabilizer. The physicochemical properties, in vitro release and in vivo pharmacokinetics of t-Res NS were investigated. The mean particle size, zeta potential, encapsulation efficiency and drug loading of t-Res NS prepared by the optimal prescription were 96.9 nm, −20.4mV, 78% and 28.1%, respectively. The morphology of t-Res nanoparticles was spherical indicated by SEM with amorphous phase verified by XRD and DSC. The t-Res NS present a good physical stability as well as enhanced chemical stability. Compared to crude drug, the in vitro dissolution rate of t-Res NS was increased with fitting Higuchi equation ( Q = 0.3215 t 1 / 2 + 0.0070 ). The in vivo pharmacokinetic test in rats showed that the AUC 0 ∼ t of t-Res NS (559.4 μg/mL·min) was about 3.6-fold higher than that of t-Res solution. Meanwhile, the MRT of t-Res nanosuspensions was longer than that of t-Res solution. These results suggested that NS may be a potentially nanocarrier for clinical delivery of t-Res. [ABSTRACT FROM AUTHOR]

Solar thermal collectors are among the most important photo-thermal energy conversion systems. Effectiveness of these systems is measured by the ability of working fluid to absorb incident radiative energy. Although nanosuspensions are considered very promising for this purpose, there is a concern about their stability and their long-term use. Electrostatic and steric stabilization methods are among the two approaches used for colloidal suspensions. In thermal applications, electrostatic stabilization is usually preferred; especially in high temperature applications. The aim of this study is to investigate, both experimentally and numerically, the effect of electrostatic stabilization on the thermal radiation transfer mechanisms in TiO 2 and Al 2 O 3 nanosuspensions. The experimental section covers nanosuspensions preparation and characterization, where the effects of electrostatic stabilization (pH and zeta potential values) on the increasing effective particle size due to agglomeration behaviour are explored. The numerical part covers the estimation of radiative properties and thermal radiation transfer based on the average particle agglomerate size obtained from the particle size distributions in the experimental part. The radiative properties are assessed using the single scattering approximation technique based on the Lorenz-Mie theory. The thermal radiation transfer is obtained by solving the radiative transfer equation by the discrete ordinate method. The results show remarkable stability behaviour under the effect of the pH value for the two nanosuspensions types. The effect of the different particle agglomerate size shows a considerable enhancement in the radiative properties specifically in the UV/Vis spectrum, which has a significant impact on the thermal radiative transfer phenomena, due to the solar spectrum. It is also shown that nanosuspensions with different particle agglomerate sizes have a significant effect on the volumetric radiative heat flux, where the radiative energy losses decrease in comparison to those of pure water. [ABSTRACT FROM AUTHOR]

The aim of this study is to develop nanosuspension of carvedilol (CRV) by wet media milling. Concentration of polymeric stabilizer (hydroxypropyl cellulose-HPC-SL), milling speed and size of milling beads were identified as critical formulation and process parameters and their effect on CRV particle size after 60 min of milling was assessed using a Box-Behnken experimental design. Optimized nanosuspension was solidified using spray drying and freeze drying and subjected to solid state characterization. Low stabilizer concentration (10%), low milling speed (300 rpm) with small milling beads (0.1 mm) were found as optimal milling conditions. Crystal lattice simulation identified potential slip plane within CRV crystals, where fractures are the most likely to occur. Calculated mechanical properties of CRV crystal indicates that low energy stress is sufficient to initiate fracture, if applied in the correct direction, explaining the advantage of using smaller milling beads. Only spray dried nanosuspension redispersed to original nanoparticles, while particle agglomeration during freeze drying prevented sample redispersion. Wet milling and spray drying did not induce polymorphic transition of CRV, while there is indication of polymorphic transition during freeze drying, making spray drying as the preferred solidification method. [ABSTRACT FROM AUTHOR]

In order to enhance the lipophilicity and thus oral bioavailability of icariin (ICA) and icariside II (ICA II) of total flavonoids of epimedium (TFE), a total flavonoids of epimedium–phospholipid complex (TFE‐PLC) is prepared by wet media milling. The stabilizers Aerosi and SDS are used to formulate TFE‐PLC nanosuspensions (TFE‐PLC–Ns) to improve the dispersion of TFE–PLC. FTIR and DSC data confirms the formation of TFE‐PLC. The oil solubility of ICA and ICA II in the complex in octanol is improved nearly four times over that in TFE. The logP of ICA in TFE‐PLC is significantly increased with a value from 1.61 to 2.02 at pH 4.5, and ICA II, from 3.24 to 4.77. The mean diameter of the TFE‐PLC‐Ns is reduced from 6.166 to 0.424 μm, and its dissolution is improved over TFE. In the in vivo evaluation, TFE‐PLC‐Ns exhibits a considerable enhancement with larger AUC0–t and shorter Tmax than TFE and TFE‐PLC. The relative bioavailability of ICA in TFE‐PLC and TFE‐PLC‐Ns are 181.75 and 249.05%, respectively, and for ICA II are 401.63 and 684.70%, respectively. Therefore, it suggests that TFE‐PLC‐Ns has possibilities in enhancing oral bioavailability of TFE, which may be due to its improved lipophilicity and wettability. Practical Applications: The oral bioavailability of ICA and ICA II in TFE are very low due to their poor lipophilicity and cell permeability. Here, TFE‐PLC‐Ns is proposed, which is prepared by wet media milling for improving lipophilic properties and oral bioavailability. In addition, some proofs of TFE‐PLC are investigated in detail, and TFE‐PLC‐Ns significantly increased the oral bioavailability of ICA and ICA II in TFE. Therefore, the authors recommend a potential drug vehicle of TFE‐PLC‐Ns for oral administration of ICA and ICA II, and a novel method of phospholipid complex preparation for industrial manufacture. In this article, the total flavonoids of epimedium–phospholipid complex (TFE‐PLC) is prepared to enhance the lipophilicity of icariin (ICA) and icariside II (ICA II) in TFE. Aerosi and SDS are used to formulate TFE‐PLC nanosuspensions (TFE‐PLC‐Ns) to improve the dispersion of TFE‐PLC. And finally, TFE‐PLC‐Ns exhibits enhanced oral bioavailability of ICA and ICA II compared with them in TFE and TFE‐PLC. [ABSTRACT FROM AUTHOR]

[Display omitted] • A comprehensive study on nanofluids preparation and their current and future applications has been reported. • Types of nanofluids have been discussed based on different nano size materials. • The stability of single and hybrid nanofluids has been reported here. • Varying thermophysical characteristics of single and hybrid nanofluids have been reported. • Heat transfer improvement of varying nanofluids using different heat exchanger geometries has been reported. Several studies have been reported on nanoparticles and their nanosuspensions including metal oxides; Graphene Oxide, carbon-based single/composites/hybrid materials which are becoming more demanding in varying applications. Conventional fluids like DW, water, EG, PEG, Palm oil, Glycerin, and Transformer oil have limited thermal and heat transfer properties, so there is a need for some alternative heat exchanging liquids. The prime aim to write this report is to synthesise nanoparticles, nanofluid preparation, varying applications, stability improvement, thermophysical characteristics and heat transfer improvement of varying nanofluids using different heat exchanger geometries. One pot Sonochemical technique was adopted to synthesise nano size particles, and then a facile 2-step preparation technique was practised to prepare nanofluids. Well dispersed and stable nanofluids proved their enhanced thermal and heat transfer properties as compared to conventional fluids, including their enhanced thermal and rheological characteristics. The stability and longer suspension of solid nanoparticles is a key challenge of the nanofluids field which has been explored here for varying nanofluids. The improvement in thermophysical and thermal properties of Metal oxides, Ceramics, Graphene oxide, and Carbon nanotubes based single and hybrid nanofluids are reported here. The 0.025%, 0.05%, 0.075%, 0.1%, 1%, 2%, and 3% weight concentrations of the solid nano size particles dispersed in base fluids showed improved thermophysical and heat transfer properties. A substantial improvement in thermal conductivity of 49%, 43.7%, 41%, 37.2%, 27%, and 17% was noticed at higher wt.% concentrations of the nanofluids. Similarly, the higher heat transfer improvement was reported up to 89%, 82% and 72%, 69%, and 57% at higher wt.% concentration for Graphene and CNTs-based nanofluids. [ABSTRACT FROM AUTHOR]

Coenzyme Q 10 (CoQ 10 ) is an antioxidant substance indicated as a dietary supplement which has been proposed as adjuvant in the treatment of cardiovascular disorders and cancer for its protective and immunostimulating activities. The aim of this work was the production by high-pressure homogenization, characterization and stability investigation of three different CoQ 10 nanosuspensions designed to be administered to the lungs by nebulization. Three surfactants, i.e. lecithin, PEG32 stearate and vitamin-E TPGS, were selected to stabilize CoQ 10 formulations. Preparations were identified as nanosuspensions (particle size in the range 35–60 nm): the smallest particles were obtained with vitamin-E TPGS and denoted a core-shell structure. The CoQ 10 delivered from a commercial air-jet nebulizer was in all the cases around 30% of the loaded dose. The nanosuspension containing PEG32 stearate presented the highest respirable fraction (70.6%) and smallest MMAD (3.02 μm). Stability tests showed that the most stable formulation, after 90 days, was the one containing vitamin-E TPGS, followed by the CoQ 10 -lecithin formulation. Interestingly, those formulations were demonstrated to be suitable also for nebulizers using other mechanisms of aerosol production such as ultrasound and vibrating mesh nebulizers. Studies focused on in vitro cellular toxicity of the formulations and their single components using A549 human lung cells showed no obvious cytotoxicity for the formulations containing lecithin and PEG 32 stearate. Vitamin-E TPGS alone was shown to be able to damage the plasma membrane, nevertheless, cell damage was decreased when vitamin-E TPGS was present in the formulation with CoQ 10 . [ABSTRACT FROM AUTHOR]

The present study was designed to improve storage stability and oral bioavailability of Ganneng dropping pills (GNDP) by transforming lignans of Herpetospermum caudigerum (HL) composed of herpetrione (HPE) and herpetin (HPN) into nanosuspension (HL-NS), the main active ingredient of GNDP, HL-NS was prepared by high pressure homogenization and lyophilized to transform into solid nanoparticles (HL nanoparticles), and then the formulated HL nanoparticles were perfused into matrix to obtain NS-GNDP by melting method. For a period of 3 months, the content uniformity, storage stability and pharmacokinetics test in vivo of NS-GNDP were evaluated and compared with regular GNDP at room temperature. The results demonstrated that uniformity of dosage units of NS-GNDP was acceptable according to the criteria of Chinese Pharmacopoeia 2015J. Physical stability of NS-GNDP was investigated systemically using photon correlation spectroscopy (PCS), zeta potential measurement, and scanning electron microscopy (SEM). There was a slight increase in particles and PI of HL-NS re-dispersed from NS-GNDP after storage for 3 months, compared with new formulated NS-GNDP, which indicated a good redispersibility of the NS-GNDP containing HL-NS after storage. Besides, chemical stability of NS-GNDP was studied and the results revealed that HPE and HPN degradation was less when compared with that of GNDP, providing more than 99% of drug residue after storage for 3 months. In the dissolution test in vitro , NS-GNDP remarkably exhibited an increased dissolution velocity compared with GNDP and no distinct dissolution difference existed within 3 months. The pharmacokinetic study showed that HPE and HPN in NS-GNDP exhibited a significant increase in AUC 0–t , C max and decrease in T max when compared with regular GNDP. These results indicated that NS-GNDP possessed superiority with improved storage stability and increased dissolution rate and oral bioavailability. [ABSTRACT FROM AUTHOR]

Long-acting or extended release parenteral dosage forms have attracted extensive attention due to their ability to maintain therapeutic drug concentrations over long periods of time and reduce administration frequency, thus improving patient compliance. It is essential to have an in vitro release (IVR) testing method that can be used to assure product quality during routine production as well as predict and understand the in vivo performance of a formulation. The purpose of this work was to develop a discriminatory in vitro release method to guide formulation and process development of long-acting parenteral (LAP) nanosuspension formulations composed of poorly water-soluble drugs (BCS class II). Injectable nanosuspension formulations were developed to serve as test articles for method development. Several different IVR methods were evaluated for their application to the formulation screening and process development including (1) USP apparatus 2, (2) dialysis and reverse dialysis sac, and (3) continuous flow-through cell (USP apparatus 4). Preliminary data shows the promising results to support the utilization of USP 4 over more widely accepted USP 2 and dialysis methods. A combination of more representative in vivo hydrodynamics and ease of maintaining sink conditions yields the USP 4 flow-through cell method a more suitable in vitro release method for nanosuspension-based LAP formulations of poorly water-soluble compounds, such as compounds A and B. [ABSTRACT FROM AUTHOR]

Resveratrol (RSV) nanosuspensions, with long term stability and targeting delivery ability, were designed and demonstrated by in vitro and in vivo model. The folate modified distearoylphosphatidyl ethanolamine-polyethylene glycol (DSPE-PEG-FA), as target delivery carrier, was synthesized and confirmed by FTIR and 1 H NMR. D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and DSPE-PEG-FA used as stabilizers formed two RSV nanosuspensions (RSV-NA and RSV-NB), which were prepared by anti-solvent precipitation method and optimized by central composite design-response surface model (CCD-RSM). The morphology of RSV nanosuspensions showed flake shapes and spherical shapes by SEM. And the distribution of particles was uniform by TEM and AFM. The two RSV nanosuspensions displayed an amorphous state, by XRPD and DSC determination. At room temperature, the optimum RSV nanosuspensions showed long term stability for 20 days. The cell proliferation and morphology study revealed that the RSV nanosuspensions significantly enhanced the in vitro cytotoxicity against A549 cells in a dose- and time-dependent manner. The recommended safe concentration was 5 μM for in vitro study. In vivo studies of the two nanosuspensions also displayed higher antitumor efficacy by reduced tumor volume and weight. Compared with the saline group, the tumor inhibition ratio of the RSV-NA was 61.53 ± 18.36% and RSV-NB was 64.61 ± 21.13%. The mice weight of the RSV-NA group and RSV-NB group was also maintained constant increasing. These results demonstrated that TPGS and DSPE-PEG-FA could be used as stabilizers for stable RSV nanosuspensions formulation with the potentiality for targeting delivery to human alveolar carcinoma cells with high stability and efficacy. [ABSTRACT FROM AUTHOR]

The present study investigates the effects of formulation and process parameters on the production of aprepitant nanosuspensions applying wet media milling and subsequent solidification. Six stabilizers were used: two brands of hydroxylpropylmethyl cellulose (HPMC E-15LV and Pharmacoat 603), hydroxypropyl cellulose (HPC-SSL), polyvinylpyrollidone (PVP), D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS 1000), Poloxamer P188 and sodium dodecyl sulfate (SDS), while two diluents (mannitol and sucrose) were incorporated prior to solidification by two methods (spray- and freeze-drying). The polymorphic purity of the raw material, the particle size of nanocrystals, and the physicochemical properties of the final dried powders were assessed. Focus was placed on the energetic aspects of the crystal structure of aprepitant in order to rationalize particle breakage during wet milling. It was found that a combination of cellulosic polymers with SDS are suitable stabilizers for the production of aprepitant nanocrystals (∼300 nm or smaller) by wet media milling. Regarding the solidification of the nanosuspensions, spray-drying is advantageous compared to freeze-drying, as it leads to the production of almost spherical individual micron-sized agglomerates of nanocrystals and few secondary agglomerates of them which are expected to exhibit improved handling behavior. Spray-dried nanocrystal agglomerates containing Pharmacoat 603 and mannitol exhibit reduced hygroscopity compared to those prepared with sucrose and HPC-SSL, making them the excipients of choice. [ABSTRACT FROM AUTHOR]

Carvedilol (CAR) in its pure state has low aqueous solubility and extremely poor bioavailability which largely limit its clinical application. The aim of the study is to improve the dissolution rate and the bioavailability of CAR via preparing nanosuspensions with different stabilizers. Antisolvent precipitation-ultrasonication technique was used here. Attempts have been made to use food protein- Whey protein isolate (WPI) as a stabilizer in CAR loaded nanosuspension and also to compare its stabilizing potential with conventional nanosuspension stabilizers such as non-ionic linear copolymer-poloxamer 188 (PLX188) and anionic surfactant-sodium dodecyl sulfate (SDS). Optimized nanosuspensions showed narrow size distribution with particle size ranging from 275 to 640 nm. Amorphous state of CAR nanocrystals which also improved the solubility by 16-, 25-, 55-fold accordingly was confirmed by powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). From scanning electron microscopy (SEM), flaky shape of PLX188 and SDS nanosuspensions could be revealed but WPI nanosuspension was sphere-shaped. Up to 70% dissolution of loaded drug was observed within 15 min in phosphate buffer (pH 6.8). A pharmacokinetic study in rats indicated that both C max and AUC 0–36 values of nanosuspensions were estimated to be 2-fold higher than those of reference, suggesting a significant increase in CAR bioavailability. [ABSTRACT FROM AUTHOR]

The clinical potential of naringenin (NRG) is compromised due to its poor aqueous solubility and low oral bioavailability. The study is aimed at addressing these issues by means of naringenin nanosuspensions (NRG-NS) formulated using polyvinylpyrrolidone (PVP K-90) as stabiliser via antisolvent sonoprecipitation method. Optimisation of sonication time, drug concentration and stabilisers was done based on particle size. Characterisation of pure NRG and NRG-NS was carried out by scanning electron microscopy, differential scanning calorimetry (DSC), x-ray powder diffractometry (XRD) and Fourier transform infrared spectroscopy (FTIR). In vitro dissolution, intestinal absorption by non-everted rat intestinal sac model and in situ single pass intestinal perfusion techniques were performed for further investigation. Nanosuspensions prepared using PVP K-90 lead to minimum particle size (117 ± 5 nm) with zeta potential of −14.6 ± 5.6 mV. The particle size was affected by increasing sonication time, concentration of stabiliser and drug. Nanosizing process converted the crystalline drug into amorphous form as predicted from DSC and XRD patterns. FTIR demonstrated the formation of hydrogen bonds between drug and polymer. NRG-NS displayed a higher dissolution amount (91 ± 4.4% during 60 min) compared to NRG powder (42 ± 0.41%). The apparent and effective permeability of NRG-NS was increased as compared to the pure NRG. The in vivo pharmacokinetics demonstrated that the C and AUC values of NRG-NS were approximately 2- and 1.8-fold superior than the pure drug. Hence, overall results confirmed nanosuspensions as promising approach for NRG delivery with high absorption in gastrointestinal tract, improved dissolution and oral bioavailability. [ABSTRACT FROM AUTHOR]

There has been limited research done on the downstream processing of nanosuspensions into solid oral dosage forms. This paper demonstrates the bead layering process with a layering level at 150% and 240%, as well as the selection and justification of the outer phase excipients for tabletability and disintegrating properties. In a previous study, an itraconazole nanosuspension stabilised by SDS and HPMC E5 was layered onto sugar beads with coating polymer HPMC VLV. In the current study, compression studies with these layered beads utilising the small bead size at 150% or 240% layering levels with outer phase cushioning excipients MCC, copovidone or isomalt were performed. Other excipients such as co-compressed crospovidone-PEG 4000; DCP functioning as a disintegrant; and HPC as a binder was also added. Target output variables were achieved with a balance between an adequate tensile strength and fast dissolution rate with a release of 99.0% (±1.0% SD) within 10 min, which is in accordance with the FDA guidance for dissolution testing. The results show that the compaction of nanosuspension-layered beads is a suitable process for processing an itraconazole nanosuspension into a solid dosage form such as a compacted tablet without compromising on drug release. [ABSTRACT FROM AUTHOR]

Estrogen receptor-β005 (ER-β005) is a novel compound developed by our group; however, its application has been greatly hindered due to its low solubility. A nanosuspension of insoluble drugs is a nanoscale colloidal dispersion that has extremely higher drug-loading compared with other nanomedicines. In this study, nanosuspensions of ER-β005 (Nano-ER-β005) stabilized by a food protein, β-casein (β-CN), were prepared via an antisolvent-precipitation method to improve oral absorption and thus promote therapeutic efficacy. Nano-ER-β005, which has a diameter of 110 nm and drug-loading of 50%, was developed. Analyses of fluorescence and circular dichroism (CD) spectra demonstrated a strong interaction between β-CN and drug particles in Nano-ER-β005, indicating that β-CN is a potent nanosuspension stabilizer. The oral bioavailability of Nano-ER-β005 was 1.6-fold greater than that of raw drug particles. Additionally, ER-β005 was confirmed to have a strong therapeutic effect against pain reactions in animal models, and inhibition of this effect was significantly increased with Nano-ER-β005 treatment. In conclusion, by using β-CN as a stabilizer, nanosuspensions of ER-β005 were developed and oral absorption was enhanced. Moreover, ER-β005 is a powerful drug that inhibits pain reactions, and its therapeutic efficacy was markedly increased in the Nano-ER-β005. [ABSTRACT FROM AUTHOR]

The objective of this study is to prepare a novel drug nanosuspension modified by a natural triterpenoid saponin (glycyrrhizin (GZ)) and evaluate its stability and redispersibility. A poorly soluble drug (andrographolide (AGE)) was used as a model drug. AGE nanosuspensions (AGE-NS) using GZ as natural stabilizer with mean particle size of 487 nm were firstly prepared by homogenization and converted into dried AGE nanosuspension powder (AGE-NP) by freeze-drying. It was found that GZ was able to prevent the aggregation of AGE nanocrystals and the freeze-dried AGE-NP could easily redisperse back to AGE-NS. It was related with special properties of GZ that possessed the interfacial property (37.02 ± 0.29 N/m) and electrostatic effect (−43.6 ± 0.9 mV) and could entrap AGE nanocrystals into its network structure. The freeze-dried AGE-NP/GZ exhibited excellent performance, compared with those combined with trehalose as matrix formers. The powder X-ray diffraction result demonstrated that GZ did not alter the AGE crystal state. The dissolution of AGE-NP/GZ (99.87%) was significantly enhanced, compared with the coarse AGE (42.35%). This study demonstrated that GZ could be used as a novel multifunctional stabilizer for production of drug nanosuspensions and provided a promising basis for further formulation development of poorly soluble drug. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop ivermectin (IVM) nanosuspensions (NSs) to improve the dissolution rate of this poorly water-soluble drug. Different NSs combining different stabilizers, i.e. poloxamer 188 (P188), polysorbate 80 (T80), polyvinylpyrrolidone (PVP), and sodium lauryl sulfate (SLS), were prepared by high-pressure homogenization. The stabilizers were selected based on the saturation solubility and IVM stability within 72 h. The screening of formulations was performed by considering the drug content within the nanosize range. The best formulation (IVM:T80:PVP 1:0.5:0.5 wt%) was characterized in terms of the particle size distribution, morphology, crystallinity, drug content, andin vitrodissolution profile. This NS was also evaluated from a stability point of view, by conditioning samples at a constant temperature and relative humidity for six months. The fresh and conditioned best NSs Z-sizes were 174.6 and 215.7 nm, respectively; while both NSs showed low polydispersity indexes. The faster dissolution rate for the IVM NS was attributed to the presence of nanoparticles and changes to the crystal structure (i.e. amorphization) that further improved solubility. The best NS had a 4-fold faster initial dissolution rate than raw IVM, and is thus a promising formulation for the treatment of human and animal parasitic diseases. [ABSTRACT FROM PUBLISHER]

Objective: To prepare and evaluate the suitable nanosuspensions of Meropenem (BCS-IV drug) to increase its solubility and dissolution. Methodology: The meropenem nanosuspensions were prepared by emulsification solvent evaporation technique by applying ultrasonic energy through probe sonicator, where the organic phase of drug solution in methanol was emulsified in aqueous phase containing hydroxy propyl methyl cellulose as solubilizer and sodium lauryl sulphate as stabilizer. The prepared nanosuspensions were characterised for particle size, zeta potential, surface morphology by SEM, drug excipient compatibility by FTIR and DSC and conducted in-vitro drug release studies. Results: Results showed that the prepared nanosuspensions were having particle size range from 1 to 1000nm and the zeta potential from -10 to -20 mVs. Scanning electron microscopic pictures revealed that the obtained nanosuspension particles were spherical in shape with surface smoothness and in-vitro drug release studies notified that the prepared nanosuspensions showed increase in solubility and dissolution of meropenem when compared with the pure form. Conclusion: The nanosuspensions of meropenem could be successfully prepared and can be concluded that the nanosuspension formulation is a promising approach to increase the solubility and dissolution of BCS-IV drugs like meropenem. [ABSTRACT FROM AUTHOR]

Poorly water-soluble drugs offer challenges in developing a formulation product with adequate bioavailability. This study took advantage of the features of nanocrystals and direct compression technologies to develop a novel solid self-nanodispersion delivery system for andrographolide (Andro) in order to increase its dissolution rate for enhancing bioavailability. Andro nanosuspensions (Andro-NS) with a particle size of about 500 nm were prepared by homogenization technology and further converted into dried nanocrystal particles (Andro-NP) via spray-drying. The solid self-nanodispersion delivery system (Andro-SNDS)-loaded Andro-NP was prepared via direct compression technology. The DSC and PXRD results demonstrated that the Andro nanocrystals retained its original crystallinity. The dissolution of the Andro-SNDS formulation was 85.87% in pure water over 30 min, better than those of the coarse Andro and physical mixture of Andro and stabilizer. And the C (299.32 ± 78.54 ng/mL) and AUC (4440.55 ± 764.13 mg/L · h) of the Andro-SNDS formulation were significantly higher ( p < 0.05) than those of the crude Andro (77.52 ± 31.73 ng/mL and 1437.79 ± 354.25 mg/L · h). The AUC of the Andro-SNDS was 3.09 times as high as that of the crude Andro. This study illustrated a novel approach to combine the features of nanocrystals and composite particles used to improve oral bioavailability of poorly soluble drug. [ABSTRACT FROM AUTHOR]

Andrographolide (Andro) is an excellent anti-inflammatory bicyclic diterpene γ-lactone. However, the poor solubility limits its application as injection for the treatment of acute inflammation. To meet the clinical needs for emergency, the Andro nanosuspensions injection was first prepared by the wet milling technique. The Andro nanosuspensions were composed of 3% Andro, 5% poloxamer 188 as the non-ionic stabilizer, 0.05% sodium deoxycholate or 0.1% sodium tauroursodeoxy cholate as the ionic stabilizer, and prepared by 350 rpm speed and 12 cycles of grinding with 0.4 mm zirconium oxide pearls. The nanosuspensions showed hexagonal morphology with particle size of 300 nm, and no change in crystalline state of Andro after milling. The nanosuspensions had a significant increase in saturation solubility, and could completely release within 0.25 h (bulk Andro within 24 h). The lyophilized product of Andro nanosuspensions with mannitol (5%) as lyoprotectant had good physical and chemical stability during the 6-month storage period. The pharmacokinetic and tissue distribution results showed that it was rapidly eliminated from the blood and largely distributed in the liver. Overall, the Andro nanosuspensions may be used as a potential formulation for the treatment of liver infections owing to its passive liver targeting function. [ABSTRACT FROM AUTHOR]

Drug nanosuspensions (NSs) show a significant potential to improve loading and release properties of the poorly water soluble drug triamcinolone acetonide (TA) from poly(hydroxyethyl methacrylate) (pHEMA) soft contact lenses. In this work, TA NSs were developed by a controlled precipitation method using a fractional factorial Plackett–Burmann design. Poloxamer 407 (PL) and polyvinyl alcohol (PVA) as stabilizing agents were selected. NSs were characterized in terms of their drug content, particle size and morphology. Results indicate that all studied factors, except homogenization speed and sonication, have significant influence on the drug incorporation yield into NSs. Drug nanoparticles showed an interesting size that may be suitable for their incorporation into topical ocular drug delivery systems, as hydrogels. pHEMA hydrogels and daily-wear Hilafilcon B commercial contact lenses (SCLs) were employed to study TA loading capacity and drug release properties using NSs as loading system. Hydrogels have been synthesised by copolymerization of 2-hydroxyethyl methacrylate (HEMA) with methacrylic acid (MA) in accordance with a previous work (García-Millán et al., 2015). Both synthesised hydrogels and SCLs were characterized in terms of their mechanical and physical properties and TA loading and release properties. Selected TA NS was further characterized by studying its physical-chemical stability during the loading process. Results show that the use of TA NSs as loading medium significantly increases drug loading capacity and release of soft contact lenses in comparison with drug saturated solution. Synthesised pHEMA hydrogels and SCLs lenses have good properties as ophthalmic drug delivery systems, but SCLs load higher quantities of drug and release TA in shorter time periods than synthesised pHEMA hydrogel. [ABSTRACT FROM AUTHOR]

It is disclosed how the sizes of rod-shaped paclitaxel-nanosuspensions (PTX-Ns) that are less than 500 nm affect their in vitro and in vivo performances. A size reduction from 500 to 160 nm enhances the cellular uptake and subsequent cytotoxicity, due to the participation of caveolae-mediated endocytosis; moreover, the ability of the PTX-Ns to penetrate tumors is well correlated with the extent to which the caveolae pathway participates in cellular uptake, as their ability to target caveolae is markedly promoted as their size decreased to 160 nm. Also, the size reduction markedly alters the in vivo performance and tumor targeting. It is disclosed that via enhanced tumor penetration and retention but not simply increased tumor accumulation, size reduction of PTX-Ns results in significant improvement in antitumor activities. Overall, this study highlights the importance of the size of the PTX-Ns and the participation of caveolae-mediated endocytosis in controlling their biological functions and will assist in the design and optimization of new nanosuspension formulations for disease therapy. [ABSTRACT FROM AUTHOR]

There is more research required to broaden the knowledge on the downstream processing of nanosuspensions into solid oral dosage forms, especially for coated nanosuspensions onto beads as carriers. This study focuses on bead layering as one approach to solidify nanosuspensions. The aim was to systematically investigate the influence of type of coating polymer (HPMC VLV vs. copovidone), bead material and bead size (sugar vs. MCC, and small vs. large) and coating thickness (50%–150% layering level) on the properties of a dried itraconazole nanosuspension. A stable itraconazole nanosuspension with a mean particle size below 200 nm was prepared and a ratio of itraconazole and coating polymer of around 1:1 was identified. XRD and DSC scans revealed that itraconazole remained mostly crystalline after the bead layering process. The fastest dissolution rate was achieved using the small bead size, sugar beads, HPMC VLV as film-forming polymer and lowest layering level, with the best formulation releasing 94.1% (±3.45% SD ) within the first 5 min. A deterioration of the release profile with increasing layering level was only observed for MCC beads and was more pronounced when copovidone was used as a coating polymer. It was observed that bead layering is a suitable method to process an itraconazole nanosuspension into a solid form without compromising release. [ABSTRACT FROM AUTHOR]

The strategy of formulating poorly soluble actives as nanosuspension has been explored by more than a thousand research papers, with some medicinal products for oral and intravenous use having reached the market or advanced clinical trials. Interestingly, there is a limited number of reports of nanosuspensions formulated for dermal and transdermal drug delivery. In the present work, a nanocrystals suspension of the fluorescent, water-insoluble dye Nile Red, is prepared through a media milling technique and exploited to characterize the fate of the nanosuspended drug when applied on the skin. More in detail, the accumulation of Nile Red nanocrystals inside the hair follicles is evidenced by scanning electron microscopy, and the diffusion of drug molecules in the different skin layers is evaluated by confocal microscopy and skin permeation studies. Overall, the combination of the analytical techniques provide a description of the mechanisms underlying dermal accumulation, and transdermal penetration of a drug formulated as a nanosuspension. [ABSTRACT FROM AUTHOR]

Development of nanosuspensions offers a promising tool for formulations involving poorly water-soluble drugs. In this study, methotrexate (MTX) nanosuspensions were prepared using a bottom-up process based on acid-base neutralization reactions. Computational studies were performed to determine structural and electronic properties for isolated molecules and molecular clusters in order to evaluate the mechanism of MTX nanoparticle formation. Computational results indicated that the clusters in zwitterionic and cationic states presented larger dimensions and higher energies of interaction between MTX molecules, which favored aggregation. In contrast, the clusters in the anionic state exhibited lower energies of interaction, indicating aggregation was less likely to occur. Experimental results indicated that the higher the HCl proportion during drug precipitation, the greater the particle size, resulting in micrometric particles (2874–7308 nm) (cationic and zwitterionic forms). However, MTX nanoparticles ranging in size from 132 to 186 nm were formed using the lowest HCl proportion during drug precipitation (anionic form). In vitro release profiles indicated that the drug release rate from nanosuspension was increased (approximately 2.6 times) over that of the raw material. Overall, computational modeling and experimental analysis were complementary and assisted in the rational design of the nanosuspension based on acid-base reactions. [ABSTRACT FROM AUTHOR]

Many lead compounds have a low solubility in water, which substantially hinders their clinical application. Nanosuspensions have been considered a promising strategy for the delivery of water-insoluble drugs. Here, denatured soy protein isolate (SPI)-coated docetaxel nanosuspensions (DTX-NS) were developed using an anti-solvent precipitation-ultrasonication method to improve the water-solubility of DTX, thus improving its intracellular delivery. DTX-NS, with a diameter of 150–250 nm and drug-loading up to 18.18%, were successfully prepared by coating drug particles with SPI. Interestingly, the drug state of DTX-NS was alterable. Amorphous drug nanoparticles were obtained at low drug-loading, whereas at a high drug-loading, the DTX-NS drug was mainly present in the crystalline state. Moreover, DTX-NS could be internalized at high levels by cancer cells and enter the cytosol by lysosomal escape, enhancing cell cytotoxicity and apoptosis compared with free DTX. Taken together, denatured SPI has a strong stabilization effect on nanosuspensions, and the drug state in SPI-coated nanosuspensions is alterable by changing the drug-loading. Moreover, DTX-NS could achieve cytosolic delivery, generating enhanced cell cytotoxicity against cancer cells. [ABSTRACT FROM AUTHOR]

ZL-004, a promising small molecule that increases white blood cell counts, was developed for extended-release nanosuspensions to improve low solubility and compliance of patients. In vivo pharmacokinetic studies of nanosuspensions with different particle sizes and administration volumes were conducted. Unexpectedly, Cmax of NS-PC-L (1156 nm) was 1.3 fold higher than NS-PB-L (836 nm), and area under plasma concentration-time curve (AUC) was similar. It suggested that in vivo behavior of nanosuspensions was influenced significantly by the original dissolved drug, which did not only rely on the particle size but also the amount of the free stabilizers. In addition, smaller administration volume (0.1 mL) achieved significantly lower Cmax and AUC than the higher volume (0.5 mL), due to the reduced amount of dissolved drug. DSC and XPRD demonstrated that the crystal forms of nanosuspensions prepared by the precipitation method and high-pressure homogenization were similar; therefore, in vivo behaviors did not show significant differences. An additional 0.15% PEG 4000 enhanced the redispersity and maintained the particle size for 3 months. Finally, a nanosuspensions with the desired initial release was achieved, which lasted approximately 32 days steadily after a single dose. AUC and t1/2 were 161.2 fold and 22.9 fold higher than oral administration.

Amorphous nanosuspensions (ANSs) enable rapid release and improved delivery of a poorly water-soluble drug; however, their preparation is challenging. Here, using hemoglobin (Hb) as a carrier, ANSs aggregated from paclitaxel (PTX)–Hb complexes were prepared to improve delivery of the hydrophobic anti-cancer agent. An affinity study demonstrated strong interaction between Hb and PTX. Importantly, the complexes could aggregate into

The drug nanosuspensions is a universal formulation approach for improved drug delivery of hydrophobic drugs and one the most promising approaches for increasing the biopharmaceutical performance of poorly water-soluble drug substances, especially for nature products. This review aimed to summarize the nanosuspensions preparation approaches and the main technological difficulties encountered in nanosuspensions development, such as guidelines for stabilizers screening, in vivo fate of the intravenously administrated nanosuspensions, and how to realize the intravenously target delivery was reviewed. Furthermore, challenges of nanosuspensions for the nature products delivery also was discussed and commented. Therefore, it hoped to provide reference and assistance for the nanosuspensions production, stabilizers usage, and predictability of in vivo fate and controllability of targeting delivery of the nature products nanosuspensions. The graphical influence of the formulation properties on the curcumin nanosuspensions penetration targeting efficacy exhibited that all the nanosuspensions loaded gels, independent on type and concentration of the gelling agent used, presented an efficient uptake of the nanosuspensions into the hair follicles. Aqueous nanosuspensions (aqueous NS), Polyacrylic acid (PAA), Hydrogels hydroxyethyl cellulose (HEC). Magnification: 100 fold and 100 µm of the scale. [Display omitted] [ABSTRACT FROM AUTHOR]

Skin conditions are amongst the most prevalent health issues in the world and come with a heavy economic, social, and psychological burden. Incurable and chronic skin conditions like eczema, psoriasis, fungal infections are linked to major morbidity in the manner of physical pain and a reduction in quality life of patients. Several drugs have difficulties for penetrating the skin due to the barrier mechanism of the skin layers and the incompatible physicochemical characteristics of the drugs. This has led to the introduction of innovative drug delivery methods. Currently, formulations depend on nanocrystals have indeed been researched for topical administration of drugs and have resulted in enhanced skin penetration. This review focuses on skin penetration barriers, modern methods to enhance topical distribution, and the use of nanocrystals to overcome these barriers. By means of mechanisms such as adherence to skin, creation of diffusional corona, targeting of hair follicles, and the generation of a greater concentration gradient throughout the skin, nanocrystals could enhance transport across the skin. Scientists working on product formulations incorporating chemicals that are "challenging-to-deliver" topically may find the most current findings to be of relevance. [Display omitted] • Skin conditions are amongst the most prevalent health issues in the world. • Several drugs have difficulties for penetrating skin due to its barrier mechanism. • Nanocrystals for topical administration resulted in enhanced skin penetration. • We discuss modern approaches to enhance topical drug delivery by nanocrystals. [ABSTRACT FROM AUTHOR]

This report examines the energetics of aggregate formation between hydroxypropyl methylcellulose (HPMC) and model ionic surfactants including sodium dodecyl sulfate (SDS) at pharmaceutically relevant concentrations using the isothermal titration calorimetry (ITC) technique and a novel treatment of calorimetric data that accounts for the various species formed. The influence of molecular weight of HPMC, temperature and ionic strength of solution on the aggregate formation process was explored. The interaction between SDS and HPMC was determined to be an endothermic process and initiated at a critical aggregation concentration (CAC). The SDS-HPMC interactions were observed to be cooperative in nature and dependent on temperature and ionic strength of the solution. Molecular weight of HPMC significantly shifted the interaction parameters between HPMC and SDS such that at the highest molecular weight (HPMC K–100 M; >240 kDa), although the general shape of the titration curve (enthalpogram) was observed to remain similar, the critical concentration parameters (CAC, polymer saturation concentration (C sat ) and critical micelle concentration (CMC)) were significantly altered and shifted to lower concentrations of SDS. Ionic strength was also observed to influence the critical concentration parameters for the SDS-HPMC aggregation and decreased to lower SDS concentrations with increasing ionic strength for both anionic and cationic surfactant-HPMC systems. From these data, other thermodynamic parameters of aggregation such as Δ H a g g ° , Δ G a g g ° , H a g g ° , Δ S a g g ° , and Δ C p were calculated and utilized to postulate the hydrophobic nature of SDS-HPMC aggregate formation. The type of ionic surfactant head group (anionic vs. cationic i.e., dodecyltrimethylammonium bromide (DTAB)) was found to influence the strength of HPMC-surfactant interactions wherein a distinct CAC signifying the strength of HPMC-DTAB interactions was not observed. The interpretation of the microcalorimetric data at different temperatures and ionic strengths while varying properties of polymer and surfactant was a very effective tool in investigating the nature and energetics of HPMC and ionic surfactant interactions. [ABSTRACT FROM AUTHOR]

Recently, genkwanin (GKA) has been shown to displayin vitroantitumor activity against some cancer cells, but its poor solubility restricted thein vivostudy and further investigation of its antitumor therapeutic efficacy. In this paper, genkwanin nanosuspensions (GKA-NSps) were successfully prepared using D-alpha tocopherol acid polyethylene glycol succinate (TPGS) as a stabilizer using the precipitation-homogenization method. The obtained GKA-NSps had an average particle size of 183.1 ± 4.4 nm, a PDI value of 0.16 ± 0.07, a zeta potential of −16.2 ± 0.1 mV, and a drug loading content of 49.36 ± 0.14%. GKA-NSps showed spherical morphology and very good stability in normal saline, phosphate buffer saline (PBS, pH 7.4), 5% glucose, artificial gastric juice, artificial intestinal juice and plasma; thus, it is suitable for both oral and intravenous administration. The resultant GKA-NSps displayed sustained drug release behavior and strongerin vitrocytotoxicity against 4T1, MCF-7, MDA-MB-453, HeLa, HepG2, BT474, and A549 cells than free GKA. Thein vivostudy in MCF-7 tumor-bearing nude mice indicated that GKA-NSps (60 mg/kg, i.v.) achieved similar therapeutic efficacy as PTX injection (8 mg/kg, i.v.) (62.09% vs. 61.27%), while the minimal lethal dose was more than 320 mg/kg, indicating good safety. By using nanotechnology, our study suggested that some antitumor flavonoids of low potency, such as GKA, are promising as safe but effective anticancer drugs. [ABSTRACT FROM AUTHOR]

Context: Curcumin (CUR) is a promising drug candidate based on its broad bioactivities and good antitumor effect, but the application of CUR is potentially restricted because of its poor solubility and bioavailability. Objective: This study aims at developing a simple and effective drug delivery system for CUR to enhance its solubility and bioavailability thus to improve its antitumor efficacy. Materials and methods:Curcumin nanosuspensions (CUR-NSps) were prepared by precipitation-ultrasonication method using mPEG2000-DSPE and soybean lecithin as a combined stabilizer. Results: CUR-NSps with a high drug payload of 67.07% were successfully prepared. The resultant CUR-NSps had a mean particle size of 186.33 ± 2.73 nm with a zeta potential of −19.00 ± 1.31 mV.In vitrocytotoxicity assay showed that CUR-NSps exhibited enhanced cytotoxicity compared to CUR solution. The pharmacokinetics results demonstrated that CUR-NSps exhibited a significantly greater AUC0–24and prolonged MRT compared to CUR injections after intravenous administration. In the biodistribution study, CUR-NSps demonstrated enhanced biodistribution compared with CUR injections in liver, spleen, kidney, brain, and tumor. The CUR-NSps also showed improved antitumor therapeutic efficacy over the injections (70.34% versus 40.03%,p < 0.01). Conclusions: These results suggest that CUR-NSps might represent a promising drug formulation for intravenous administration of CUR for the treatment of cancer. [ABSTRACT FROM AUTHOR]

Nanosuspensions (NS) can enhance the saturation solubility and dissolution velocity of poorly soluble drugs. PEG as a non-ionic surfactant plays an important role in surface modification of nanoparticles for prolonging in vivo circulation. In this study, anti-solvent precipitation method was introduced to prepare gambogenic acid nanosuspensions (GNA-NS) with PVPK30 and PEG2000 as stabilizers to settle the disadvantages of GNA. The obtained nanoparticles were spherical with a mean particle size of 183.7 nm and a zeta potential of −22.8 mV. The entrapment efficiency and drug loading of the resultant formulation were 97.3 and 29.73%. X-ray diffraction analysis confirmed the amorphous phase of GNA in NS. Fourier transform infrared indicated there may be hydrogen bond interaction between the drug and excipients. After lyophilization of GNA-NS, the freeze-dried powder displayed sufficient long-term physical stability at 4 and 25 °C. In comparison to GNA solution, in vitro studies of GNA-NS showed much slower release and higher cytotoxicity in HepG2 cells. What's more, the pharmacokinetic study in rats revealed that the AUC0–∞ and t1/2 of GNA-NS were increased 2.63- and 1.77-fold than that of the reference formulation. Taken together, in vitro/in vivo evaluations showed NS would be an effectively strategy to change the poor aqueous solubility and prolong the half-life for GNA. The GNA-NS with enhanced bioavailability and drug efficacy provided a promising delivery system for the application of GNA. [ABSTRACT FROM AUTHOR]

The majority of drugs obtained through synthesis and development show poor aqueous solubility and dissolution velocity, resulting in reduced bioavailability of drugs. Most of these problems arise from formulation‑related performance issues, and an efficient way to overcome these obstacles and to increase dissolution velocity is to reduce the particle size of drug substances to form drug nanosuspensions. Materials and Methods: Danazol nanosuspensions were prepared by wet milling (WM) and high‑pressure homogenization (HPH) methods. The nanosuspensions obtained using these fabrication methods were analyzed for their particle size, surface charge, and the crystallinity of the product was assessed by X‑ray diffraction (XRD) and differential scanning calorimetry techniques. To determine in vitro and in vivo performances of the prepared nanosuspensions, dissolution velocity, and bioavailability studies were performed. Results: Particle size and zeta potential analysis showed the formation of nanosized particles with a negative charge on the surface. XRD depicted the nanocrystalline nature of danazol with low diffraction intensities. With increased surface area and saturation solubility, the nanosuspensions showed enhanced dissolution velocity and oral bioavailability in rats when compared to the bulk danazol suspension. Conclusions: The results suggest that the preparation of nanosuspensions by WM or HPH is a promising approach to formulate new drugs or to reformulate existing drugs with poorly water‑soluble properties. [ABSTRACT FROM AUTHOR]