Pharmaceutical Strategies for Stabilizing Drug Nanocrystals

2018 ◽  
Vol 24 (21) ◽  
pp. 2362-2374 ◽  
Author(s):  
Hyerim Yang ◽  
Hyeongmin Kim ◽  
Sumin Jung ◽  
Hyeyeon Seo ◽  
Shofa Khoirun Nida ◽  
...  

Background: Nanocrystallization technologies have been widely studied in recent years, as the formulation of drug nanocrystals solves problems of poor drug solubility and bioavailability. However, drug nanocrystals in the size range of 1–1000 nm usually need to be accompanied by stabilizers, such as polymers or surfactants, to enhance their stability. Despite their simplicity, improved dissolution rate, and enhanced bioavailability, the limited stability of nanocrystal formulations has prevented further development. Objective: The most effective way to handle this instability is to use stabilizers. This paper reviews various factors to consider for the production of stable drug nanocrystals and provides suggestions to overcome the problems associated with instability, such as aggregation and Ostwald ripening. Through various examples of stabilizers acting via electrostatic and steric stabilization, this review highlights the scope of enhancing the stability of drug nanocrystals. Conclusion: Studies on stabilizers used in the production of drug nanocrystals are ongoing; various factors, such as the effect of zeta potential on the stability of drug nanosuspensions, have already been revealed. However, it is necessary to determine the most appropriate stabilizer experimentally based on the various mechanisms and factors have been reviewed since the possible interactions between each drug and stabilizer are diverse.

2013 ◽  
Vol 684 ◽  
pp. 12-15 ◽  
Author(s):  
Chutamas Uthumpa ◽  
Ratana Indranupakorn ◽  
Rathapon Asasutjarit

The aim of the study was to enhance the stability of 6-gingerol, a major constituent in ginger extract, using nanoemulsion formulations. The effects of extraction techniques and solvents on the content of 6-gingerol in ginger powders were investigated. Assessments of three commonly used extraction techniques (maceration, sonication and soxhlet extraction) with two different extraction solvents (methanol and acetone) were used in this study. The highest of 6-gingerol content was obtained by using soxhlet extraction with acetone. Nanoemulsions were prepared from a mixture of oil phase (coconut oil and squalene), Cremophor® ELP, acetone and ginger extract by spontaneous emulsification method. Effect of coconut oil and squalene mass ratio on nanoemulsion formations were evaluated for the further optimization of the system, which characterized by droplet size, polydispersity index (PI), zeta potential and Oswald ripening. Stability studies at 4°C and ambient temperature for 3 months were performed. The formulation containing the mass of coconut oil to squalene ratio of 0.8:0.2 was stable and had the required droplet size (122.2+2.2 nm) in relation with PI of 0.18+0.07, zeta potential of -20.8+0.4 mV and Ostwald ripening of 0.11 nm.day-1. Negative-staining transmission electron microscopy (TEM) was used to image the emulsion droplets. Stability test under heating-cooling cycle also performed on optimized nanoemulsion. Then, the sample was analysed for 6-gingerol content. The percentage of the remaining 6-gingerol of optimized nanoemulsion was 90.89. Hence, it was concluded that the stability of 6-gingerol could be enhanced by using nanoemulsion formulation.


Author(s):  
Y. Feng ◽  
X. Y. Cai ◽  
R. J. Kelley ◽  
D. C. Larbalestier

The issue of strong flux pinning is crucial to the further development of high critical current density Bi-Sr-Ca-Cu-O (BSCCO) superconductors in conductor-like applications, yet the pinning mechanisms are still much debated. Anomalous peaks in the M-H (magnetization vs. magnetic field) loops are commonly observed in Bi2Sr2CaCu2Oy (Bi-2212) single crystals. Oxygen vacancies may be effective flux pinning centers in BSCCO, as has been found in YBCO. However, it has also been proposed that basal-plane dislocation networks also act as effective pinning centers. Yang et al. proposed that the characteristic scale of the basal-plane dislocation networksmay strongly depend on oxygen content and the anomalous peak in the M-H loop at ˜20-30K may be due tothe flux pinning of decoupled two-dimensional pancake vortices by the dislocation networks. In light of this, we have performed an insitu observation on the dislocation networks precisely at the same region before and after annealing in air, vacuumand oxygen, in order to verify whether the dislocation networks change with varying oxygen content Inall cases, we have not found any noticeable changes in dislocation structure, regardless of the drastic changes in Tc and the anomalous magnetization. Therefore, it does not appear that the anomalous peak in the M-H loops is controlled by the basal-plane dislocation networks.


Author(s):  
A.M. Zetty Akhtar ◽  
M.M. Rahman ◽  
K. Kadirgama ◽  
M.A. Maleque

This paper presents the findings of the stability, thermal conductivity and viscosity of CNTs (doped with 10 wt% graphene)- TiO2 hybrid nanofluids under various concentrations. While the usage of cutting fluid in machining operation is necessary for removing the heat generated at the cutting zone, the excessive use of it could lead to environmental and health issue to the operators. Therefore, the minimum quantity lubrication (MQL) to replace the conventional flooding was introduced. The MQL method minimises the usage of cutting fluid as a step to achieve a cleaner environment and sustainable machining. However, the low thermal conductivity of the base fluid in the MQL system caused the insufficient removal of heat generated in the cutting zone. Addition of nanoparticles to the base fluid was then introduced to enhance the performance of cutting fluids. The ethylene glycol used as the base fluid, titanium dioxide (TiO2) and carbon nanotubes (CNTs) nanoparticle mixed to produce nanofluids with concentrations of 0.02 to 0.1 wt.% with an interval of 0.02 wt%. The mixing ratio of TiO2: CNTs was 90:10 and ratio of SDBS (surfactant): CNTs was 10:1. The stability of nanofluid checked using observation method and zeta potential analysis. The thermal conductivity and viscosity of suspension were measured at a temperature range between 30˚C to 70˚C (with increment of 10˚C) to determine the relationship between concentration and temperature on nanofluid’s thermal physical properties. Based on the results obtained, zeta potential value for nanofluid range from -50 to -70 mV indicates a good stability of the suspension. Thermal conductivity of nanofluid increases as an increase of temperature and enhancement ratio is within the range of 1.51 to 4.53 compared to the base fluid. Meanwhile, the viscosity of nanofluid shows decrements with an increase of the temperature remarks significant advantage in pumping power. The developed nanofluid in this study found to be stable with enhanced thermal conductivity and decrease in viscosity, which at once make it possible to be use as nanolubricant in machining operation.


Author(s):  
Rupali L. Shid ◽  
Shashikant N. Dhole ◽  
Nilesh Kulkarni ◽  
Santosh L Shid

Poor water solubility and slow dissolution rate are issues for the majority of upcoming and existing biologically active compounds. Simvastatin is poorly water-soluble drug and its bioavailability is very low from its crystalline form. The purpose of this study wasto increase the solubility and dissolution rate of simvastatin by the  preparation of nanosuspension by emulsification solvent diffusion method at laboratory scale. Prepared nanosus-pension was evaluated for its particle size and in vitro dissolution study and characterized by zeta potential,differential scanning calorimetry (DSC) and X-Ray diffractometry (XRD), motic digital microscopy, entrapment efficiency, total drug content, saturated solubility study and in vivo study. A 23 factorial design was employed to study the effect of independent variables, amount of SLS (X1), amount of PVPK-30 (X2) and poloxamer-188 (X3) and dependent variables are total drug content and polydispersity Index. The obtained results showed that particle size (nm) and rate of dissolution has been improved when nanosuspension prepared with the higherconcentration of PVPK-30 with the higher concentration of PVP K-30 and Poloxamer-188 and lower concentration of SLS. The particle size and zeta potential of optimized formulation was found to be 258.3 nm and 23.43. The rate of dissolution of the optimized nanosuspension was enhanced (90% in 60min), relative to plain simvastatin  (21% in 60 min), mainly due to the formation of nanosized particles. These results indicate the suitability of 23 factorial  design for preparation of simvastatin loaded nano-suspension significantly improved in vitro dissolution rate and thus possibly enhance fast onset of therapeutic drug effect. In vivo study shows increase in bioavailability in nanosuspension formulation than the plain simvastatin drug.


Foods ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1637
Author(s):  
Yunjiao Zhao ◽  
Rui Liu ◽  
Cuiping Qi ◽  
Wen Li ◽  
Mohamed Rifky ◽  
...  

The active components in garlic essential oil are easily degradable, which limits its application in the food industry. Vegetable oils (VOs) were used to improve the stability of garlic essential oil (GEO) emulsion. The volatile compounds of GEO and its mixtures with vegetable oils (VOs), including corn oil (CO), soybean oil (SO), and olive oil (OO) indicated that GEO-VO mixtures had a higher percentage of Diallyl disulfide and Diallyl trisulfide than pure GEO. Adding an appropriate amount of VOs promoted the GEO emulsion (whey protein concentrate and inulin as the wall materials) stability in order of CO > SO > OO. Evaluation of the encapsulation efficiency, controlled release, and antimicrobial activity of GEO-VO microcapsules showed that the GEO was successfully entrapped and slowly released with active antibacterial activities on both E. coli and S. aureus. Collectively, these results implied that VOs, especially for 20% CO, improved the stability of GEO emulsions and the encapsulation efficiency of GEO microcapsules. The mechanism might be related to (1) the regulating effect of density difference between oil and water phases on prevention to gravitational separation, (2) the promotion to the compatibility of GEO and VOs to inhibit the phase separation caused by Ostwald ripening.


Foods ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1657
Author(s):  
Karolina Östbring ◽  
María Matos ◽  
Ali Marefati ◽  
Cecilia Ahlström ◽  
Gemma Gutiérrez

Rapeseed press cake (RPC), the by-product of rapeseed oil production, contains proteins with emulsifying properties, which can be used in food applications. Proteins from industrially produced RPC were extracted at pH 10.5 and precipitated at pH 3 (RPP3) and 6.5 (RPP6.5). Emulsions were formulated at three different pHs (pH 3, 4.5, and 6) with soy lecithin as control, and were stored for six months at either 4 °C or 30 °C. Zeta potential and droplet size distribution were analyzed prior to incubation, and emulsion stability was assessed over time by a Turbiscan instrument. Soy lecithin had significantly larger zeta potential (−49 mV to 66 mV) than rapeseed protein (−19 mV to 20 mV). Rapeseed protein stabilized emulsions with smaller droplets at pH close to neutral, whereas soy lecithin was more efficient at lower pHs. Emulsions stabilized by rapeseed protein had higher stability during storage compared to emulsions prepared by soy lecithin. Precipitation pH during the protein extraction process had a strong impact on the emulsion stability. RPP3 stabilized emulsions with higher stability in pHs close to neutral, whereas the opposite was found for RPP6.5, which stabilized more stable emulsions in acidic conditions. Rapeseed proteins recovered from cold-pressed RPC could be a suitable natural emulsifier and precipitation pH can be used to monitor the stability in emulsions with different pHs.


Reproduction ◽  
2007 ◽  
Vol 133 (6) ◽  
pp. 1095-1106 ◽  
Author(s):  
G P Redding ◽  
J E Bronlund ◽  
A L Hart

Mathematical modelling was used to investigate oxygen transport in the developing ovarian follicle. In contrast to previous findings, the results show that oxygen can reach the oocyte in large preantral follicles. This is largely due to the inclusion of fluid voidage in the model and improved estimates of oxygen diffusion coefficients through the granulosa. The results also demonstrate that preantral follicles will eventually reach a size beyond which further growth will result in the follicle becoming increasingly anoxic. The predicted size range at which this occurs is consistent with the size range at which antrum formation is observed in many mammals. This suggests that the antrum formation stage of follicular growth may be pivotal to the further development and ultimate fate of the follicle, and that antrum formation itself may represent a mechanism by which the follicle can overcome oxygen limitations. This was supported through extension of the model to the antral follicle, which showed that antrum formation can provide a way in which the follicle can continue to grow and yet avoid becoming hypoxic. The results of the model were consistent with observed follicle development.


2011 ◽  
Vol 194-196 ◽  
pp. 2365-2375
Author(s):  
Jai Houng Leu ◽  
Li Fong Wu ◽  
Ay Su

This research investigated and explored the overall technical and legal suggestions on mixed ash (bottom ash + fly ash) from the first BOT(built-operation then transfer) incineration plant in south Taoyuan of Taiwan, with the hope of serving as the reference for treating ash from urban refuse incinerator and making sustainable operation management policies in Taiwan. Both bottom ash and fly ash contain high-content harmful metals like lead, chrome, and cadmium, with the lead content exceeding standard value. Plasma fusing technology may effectively settle toxic heavy metals and reduce their dissolution rate. The results show that the increase in percentage of bottom ash could maintain post-fusing strength and produce solidification effect, but this reduced the stability of toxic heavy metals and raised their dissolution rate. Suitable mixture ratio of bottom ash and fly ash was 2:1, volume reduction ratio 0.349, and weight reduction ratio 0.4936. The mixture was fulvous and dense with gloss and adequate strength. The dissolution test of lava products complied with national standards, and they might be used for recycling aggregates and solidifying cement.


2021 ◽  
Vol 901 ◽  
pp. 117-122
Author(s):  
Netnapa Ontao ◽  
Sirivan Athikomkulchai ◽  
Sarin Tadtong ◽  
Phuriwat Leesawat ◽  
Chuda Chittasupho

Ocimum gratissimum L. leaf oil exhibited many pharmacological properties. This study aimed to formulate and evaluate the physical and chemical stability of O.gratissimum leaf oil nanoemulsion. O.gratissimum leaf oil was extracted by hydrodistillation. The major component of the essential oil eugenol, was analyzed by UV-Vis spectrophotometry. Nanoemulsions of O.gratissimum leaf oil were formulated using polysorbate 80, hyaluronic acid, poloxamer 188, and deionized water by phase inversion composition method. The hydrodynamic diameter, polydispersity index, and zeta potential value of O.gratissimum leaf oil nanoemulsion was evaluated by a dynamic light scattering technique. The %remaining of eugenol in the nanoemulsion was analyzed by UV-Vis spectrophotometry. The essential oil extracted from of O. gratissimum leaf oil was a clear, pale yellow color. The %yield of the essential oil was 0.15 ± 0.03% v/w. The size of the nanoemulsion was less than 106 nm. The polydispersity index of the nanoemulsion was ranging from 0.303 - 0.586 and the zeta potential value of the nanoemulsion was closely to zero, depending on the formulation component. O. gratissimum leaf oil at concentrations ranging from 0.002 - 0.012% v/v contained 35 - 41% of eugenol. The size of nanoemulsion was significantly decreased after storage at 4 °C, while significantly increased upon storage at 45 °C. The size of nanoemulsion stored at 30 °C did not significantly change. The %remaining of eugenol in the nanoemulsion was more than 90% after storage at 4 °C and 30 °C for 28 days. The percentage of eugenol remaining in the nanoemulsion stored at 45 °C was more than 85 - 90%, suggesting that the temperature affected the stability of eugenol in the nanoemulsion.


1997 ◽  
Vol 84 (3_suppl) ◽  
pp. 1373-1374
Author(s):  
Jack Kasar

The Professional Development Assessment was constructed and pilot-tested with 76 students in three occupational therapy programs. A comparison of pretest and posttest scores yielded a significant correlation of .48, supporting the stability of responding over 1 to 2 years and suggesting usefulness of further development for evaluation of professional behaviors in students.


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