Bead Mill Research Articles

Production of drug nanosuspensions: effect of drug physical properties on nanosizing efficiency

Objective: Drug nanosuspension is one of the established methods to improve the bioavailability of poorly soluble drugs. Drug physical properties aspect (morphology, solid state, starting size et al) is a critical parameter determining the production efficiency. Some drug modification approaches such as spray-drying were proved to improve the millability of drug powders. However, the mechanism behind those improved performances is unclear. This study is to systematically investigate the influence of those physical properties.Methods: Five different APIs (active pharmaceutical ingredients) with different millabilities, i.e. resveratrol, hesperetin, glibenclamide, rutin, and quercetin, were processed by standard high pressure homogenization (HPH), wet bead milling (WBM), and a combinative method of spray-drying and HPH.Results: Smaller starting sizes of certain APIs could accelerate the particle size reduction velocity during both HPH and WBM processes. Spherical particles were observed for almost all spray-dried powders (except spray-dried hesperetin) after spray-drying. The crystallinity of some spray-dried samples such as rutin and glibenclamide became much lower than their corresponding unmodified powders. Almost all spray-dried drug powders after HPH processes could lead to smaller nanocrystal particle size than unmodified APIs.Conclusion: The modified microstructure instead of solid state after spray-drying explained the potential reason for improved nanosizing efficiency. In addition, the contribution of starting size on the production efficiency was also critical according to both HPH and WBM results.

Solidification of hesperidin nanosuspension by spray drying optimized by design of experiment (DoE)

Objective: To accelerate the determination of optimal spray drying parameters, a “Design of Experiment” (DoE) software was applied to produce well redispersible hesperidin nanocrystals.Significance: For final solid dosage forms, aqueous liquid nanosuspensions need to be solidified, whereas spray drying is a large-scale cost-effective industrial process.Methods: A nanosuspension with 18% (w/w) of hesperidin stabilized by 1% (w/w) of poloxamer 188 was produced by wet bead milling. The sizes of original and redispersed spray-dried nanosuspensions were determined by laser diffractometry (LD) and photon correlation spectroscopy (PCS) and used as effect parameters. In addition, light microscopy was performed to judge the redispersion quality.Results: After a two-step design of MODDE 9, screening model and response surface model (RSM), the inlet temperature of spray dryer and the concentration of protectant (polyvinylpyrrolidone, PVP K25) were identified as the most important factors affecting the redispersion of nanocrystals. As predicted in the RSM modeling, when 5% (w/w) of PVP K25 was added in an 18% (w/w) of hesperidin nanosuspension, subsequently spray-dried at an inlet temperature of 100 °C, well redispersed solid nanocrystals with an average particle size of 276 nm were obtained. By the use of PVP K25, the saturation solubility of the redispersed nanocrystals in water was improved to 86.81 µg/ml, about 2.5-fold of the original nanosuspension. In addition, the dissolution velocity was accelerated.Conclusions: This was attributed to the additional effects of steric stabilization on the nanocrystals and solubilization by the PVP polymer from spray drying.

Systematical Investigation of Different Drug Nanocrystal Technologies to Produce Fast Dissolving Meloxicam Tablets.

Three different methods, i.e., high-pressure homogenization, wet bead milling, and a combination approach of freeze-drying and high-pressure homogenization, were used to produce meloxicam nanosuspensions, respectively. Wet bead milling led to the nanosuspensions with smallest particle size (88nm) after 4h and optimal dissolution performances. Freeze-dried meloxicam powder could highly improve the size reduction efficiency compared to the unmodified drug and particle size of the freeze-dried sample could be reduced to 342nm after only one homogenization cycle at 1000bar. The polymorphism transition and change of the particle morphology after the lyophilization might be important reasons to affect the nanosizing processes. Interestingly, the tablets prepared by using nanosuspensions from homogenizer and combination process showed faster dissolution in the first 20min than the bead milling nanocrystal tablets.

Co-instillation of nano-solid magnesium hydroxide enhances corneal permeability of dissolved timolol

We prepared magnesium hydroxide (MH) nanoparticles by a bead mill method, and investigated whether the co-instillation of MH nanoparticles improves the low transcorneal penetration of water-soluble drugs, such as the anti-glaucoma eye drug timolol maleate (TM). MH particle size was decreased by the bead mill treatment to a mean particle size of 71 nm. In addition, the MH nanoparticles were highly stable. Next, we demonstrated the effect of MH nanoparticles on the corneal surface. MH shows only slight solubility in lacrimal fluid, and the instillation of MH nanoparticles for 14 days did not affect the behavior (balance of secretion and excretion) of the lacrimal fluid in rabbit corneas. Moreover, there was no observable corneal toxicity of MH nanoparticles, and treatment with MH nanoparticles enhanced the intercellular space ratio in the eyes of rats. MH alone did not permeate into the cornea; however, the co-instillation of MH nanoparticles and dissolved TM (nMTFC) enhanced the corneal penetration of TM. In addition, the intraocular pressure (IOP)-reducing effect of nMTFC was significantly higher than those of the TM solution or the co-instillation of MH microparticles and TM. In conclusion, we found that MH nanoparticles enhance the corneal penetration of dissolved TM with no observable corneal stimulation or obstruction of the nasolacrimal duct by the MH nanoparticles. It is possible that the co-instillation of MH nanoparticles may provide a useful way to improve the bioavailability of water-soluble drugs in the ophthalmic field. These findings provide significant information that can be used to design further studies aimed at developing anti-glaucoma eye drugs.

Emergent composite structures following the amorphization of itraconazole with α-glucosyl rutin by over-grinding

We investigated the use of α-glucosyl rutin (rutin-G) as a grinding aid for wet bead milling. Itraconazole (ITCZ), which has low solubility at physiological pH conditions, was used as a model poorly water-soluble drug. Pulverization of ITCZ with rutin-G effectively improved the dissolution profile of ITCZ relative to other grinding aids, whereas excess pulverization of ITCZ with rutin-G led to a decrease in the dissolution rate of ITCZ. The structures of these pulverized samples were evaluated by powder X-ray diffraction (PXRD) and small-angle X-ray scattering (SAXS) to better understand this unexplained phenomenon. The PXRD pattern of ITCZ with rutin-G after milling for 10h was dramatically different from the patterns of ITCZ ground for shorter times. The results imply that the molecular-level middle-range ordering of the rutin-G and ITCZ mixture was almost unchanged for different milling time increments up to 5h, whereas the sample milled for 10h showed structural changes in the middle-range order. Furthermore, an analysis of the SAXS measurements suggested a change in the composite structures from large μm-size particles through a molecular-level local atomic arrangement of each particle via a molecular reaction between ITCZ and rutin-G as the milling time progressed. The decrease in dissolution rate after 5h may be related to the formation of the new composite structures between ITCZ and rutin-G. Excess pulverization caused by the addition of rutin-G may induce structural changes in the drug undergoing milling.

Dispersion and Shape Control on Nanoparticles of Gd2O3:Eu3+ Red Phosphor Prepared by Template Method

Gd2O3:Eu3+ red phosphors were prepared by template method from crystalline cellulose impregnated by metal salt. The crystallite size and photoluminescence(PL) property of Gd2O3:Eu3+ red phosphors were controlled by varying the calcination temperature and Eu3+ mol ratio. The nano dispersion of Gd2O3:Eu3+ was also conducted with a bead mill wet process. Dependent on the time of bead milling, Gd2O3:Eu3+ nanosol of around 100 nm (median particle size : D50) was produced. As the bead milling process proceeded, the luminescent efficiency decreased due to the low crystallinity of the Gd2O3:Eu3+ nanoparticles. In spite of the low PL property of Gd2O3:Eu3+ nanosol, it was observed that the photoluminescent property was recovered after re-calcination. In addition, in the dispersed nanosol treated at 85 °C, a self assembly phenomenon between particles appeared, and the particles changed from spherical to rod-shaped. These results indicate that particle growth occurs due to mutual assembly of Gd(OH)3 particles, which is the hydration of Gd2O3 particles, in aqueous solvent at 85 °C.

Therapeutic Effect of Cilostazol Ophthalmic Nanodispersions on Retinal Dysfunction in Streptozotocin-Induced Diabetic Rats.

We previously prepared ophthalmic formulations containing cilostazol (CLZ) nanoparticles by bead mill methods (CLZnano), and found that instillation of CLZnano into rat eyes supplies CLZ into the retina. In this study, we investigated changes in the electroretinograms (ERG) of streptozotocin-induced diabetic rats (STZ rats), a model of diabetes mellitus. In addition, we demonstrated that dispersions containing CLZ nanoparticles attenuate changes in the ERG of STZ rats. The instillation of CLZnano had no effect on body weight or plasma glucose and insulin levels. Furthermore, no corneal toxicity was observed in the in vivo study using STZ rats. The a-wave and b-wave levels in addition to oscillatory potentials (OP) amplitude decreased in STZ rats two weeks after the injection of streptozotocin, with the instillation of CLZnano attenuating these decreases. In addition, the level of vascular endothelial growth factor (VEGF) in the retinas of STZ rats was 9.26-fold higher than in in normal rats, with this increase also prevented by the instillation of CLZnano Thus, we have found that a-wave and b-wave levels in addition to OP amplitude are decreased in rats following the injection of excessive streptozotocin. Furthermore, the retinal disorders associated with diabetes mellitus are attenuated by the instillation of CLZnano. These findings provide significant information that can be used to design further studies aimed at developing anti-diabetic retinopathy drugs.

Dermal miconazole nitrate nanocrystals – formulation development, increased antifungal efficacy & skin penetration

Miconazole nitrate nanosuspension was developed to increase its antifungal activity and dermal penetration. In addition, the nanosuspension was combined with the synergistic additive chlorhexidine digluconate. The production was performed by wet bead milling and both production and formulation parameters were optimized. A stabilizer screening revealed poloxamer 407 and Tween 80 both at 0.15% as the most effective stabilizers for miconazole nanosuspensions at 1.0%. The nanocrystals were incorporated into a hydroxypropyl cellulose gel base. Short-term stability (3months) of the nanocrystal bulk population could be shown at room temperature and fridge. Besides the stable bulk nanocrystals, some longitudinal crystal growth to needle like crystals occurred. The addition of ionic compounds as the chlorhexidine digluconate often destabilizes suspensions. Surprisingly here, the addition minimized the crystal growth. An underlying mechanism is proposed. An inhibition zone assay was performed using Candida albicans (ATCC® 10231™). When comparing the nanocrystals in suspension and in gel to μm-sized miconazole nitrate formulations and two market products, the increase in inhibition zone diameter for the nanosuspension formulations was most pronounced in the chlorhexidine digluconate free formulations. These nanocrystal formulations were closely or similarly effective as the microsuspensions and the market products containing the synergistic chlorhexidine digluconate, showing the potential of the nanosuspension formulation. Nanosuspension performance was even further increased when chlorhexidine digluconate was added. Ex-vivo skin penetration studies on porcine ears revealed distinctly less remaining miconazole nitrate on the skin surface for nanocrystals (e.g., 76–86%) compared to market products (e.g. 94%). Also, penetration was increased e.g. in skin depth of 5–10μm from <1.0/1.7% to e.g. 3.3–6.2% for nanocrystals.

Disintegration of Nannochloropsis sp. cells in an improved turbine bead mill

The Nannochloropsis sp. cells in aqueous solution were disintegrated in an improved bead mill with turbine agitator. The disintegration rates of cell samples disrupted under various operating parameters (i.e., circumferential speed, bead size, disintegration time, and cell concentration) were analyzed. An experimental strategy to optimize the parameters affecting the cell disintegration process was proposed. The results show that Nannochloropsis sp. cells can be effectively disintegrated in the turbine stirred bead mill under the optimum condition (i.e., circumferential speed of 2.3m/s, concentration of 15vol.%, disintegration time of 40min and bead size of 0.3–0.4mm). The disintegration mechanism was discussed via the selection and breakage functions from population balance modelling. It is revealed that the impact and compression effects of stirring beads are more effective for the disruption of coarser fraction of cells, and the shear effect dominates the production of finer fractions of disintegrated cells.

Low-temperature synthesis of zircon by soft mechano–chemical activation-assisted sol–gel method

Zircon (i.e., ZrSiO4) was synthesized by a sol–gel route at a low temperature with assistance of soft mechano–chemical activation of derived precursors in a high-energy density stirred bead mill. The reaction of precursors pretreated by soft mechano–chemical at different time in sol–gel process was analyzed. The samples were characterized by X-ray diffraction, Fourier transfer infrared spectroscopy, nitrogen gas adsorption method (BET), thermogravimetry, scanning electron microscopy and high-resolution 29Si nuclear magnetic resonance spectroscopy. The results show that zircon powder with a high crystallinity and a small grain size can be formed via soft mechano–chemical pre-activation and sol–gel route at a lower temperature. The specific surface area of calcined powder increases and the average crystalline size and mean surface particle size decreases with increasing the soft mechano–chemical treatment time. It is indicated that the soft mechano–chemical activation can accelerate the dehydration/dehydroxylation reactions, reduce the bonding degree of Si–O bonds, and break a certain extent of [SiO4]4− tetrahedral three-dimensional network, which is formed in the sol–gel reaction, thus enhancing the reactivity of precursors and facilitating the formation of ZrSiO4 from Zr4+ ions with [SiO4]4− tetrahedra during the subsequent thermal treatment at a lower temperature (i.e., 700 °C). XRD patterns of all the ground precursors fired at 700 °C. Soft mechano–chemical activation of precursor prepared in sol–gel route could decrease the subsequent sintering temperature of ZrSiO4. Compared to the precursor unactivated, ZrSiO4 powder with a high crystallinity was formed at a lower sintering temperature (i.e., 700 °C) for the precursor activated for 6 h.

Effect of preparation process of microfibrillated cellulose-reinforced polypropylene upon dispersion and mechanical properties

Microfibrillated cellulose (MFC)-reinforced polypropylene (PP) was prepared via two engineering approaches: disintegration of the pulp by a bead mill followed by a melt-compounding process with PP (B-MFC-reinforced PP); and disintegration of the pulp mixed with PP by a twin screw extruder followed by a melt-compounding process (T-MFC-reinforced PP). The effects that the engineering process and the microfibrillation of the pulp had upon the dispersion and mechanical properties were investigated through tensile tests, rheological analysis and X-ray computed tomography. The bead-milling method enabled a uniform microfibrillation of the pulp to under 100 nm, which corresponded to a surface area of 133–146 m2/g for the pulp, found by the Brunauer–Emmett–Teller (BET) analysis. The T-MFC-reinforced PP with 30 wt% MFC content exhibited a tensile modulus of 5.3 GPa and a strength of 85 MPa, whereas the B-MFC-reinforced PP composites with the same content of MFC exhibited values of 4.1 GPa and 59.6 MPa, respectively. Rheological analysis revealed that the complex viscosity and storage modulus at 170 °C of T-MFC-reinforced PP with 30 wt% MFC content are 5–7 and 5–8 times higher than that of B-MFC-reinforced PP, respectively. This indicated that T-MFC was more dispersed in the PP than B-MFC. Therefore, T-MFC produced a more rigid interconnected network in the matrix during the melting state than B-MFC.

Microscale disruption of microorganisms for parallelized process development.

Escherichia coli, Saccharomyces cerevisiae, and Pichia pastoris are the standard platforms for biopharmaceutical production with 40% of all between 2010 to 2014 approved protein drugs produced in those microbial hosts. Typically, products overexpressed E. coli and S. cerevisiae remain in the cytosol or are secreted into the periplasm. Consequently, efficient cell disruption is essential for high product recovery during microbial production. Process development platforms at microscale are essential to shorten time to market. While high-pressure homogenization is the industry standard for cell disruption at large scale this method is not practicable for experiments in microscale. This review describes microscale methods for cell disruption at scales as low as 200 µL. Strategies for automation, parallelization and miniaturization, as well as comparability of the results at this scale to high pressure homogenization are considered as those criteria decide which methods are most suited for scale down. Those aspects are discussed in detail for protein overexpression in E. coli and yeast but also the relevance for alternative products and host such as microalgae are taken into account. The authors conclude that bead milling is the best comparable microscale method to large scale high-pressure homogenization and therefore the most suitable technique for automated process development of microbial hosts with the exception of pDNA production.

A Method for the Activation of Platelet-Rich Plasma via Bead Mill Homogenizer for Mesenchymal Stem Cell Culture.

Activated platelet-rich plasma (PRP) has been studied as a replacement for fetal bovine serum (FBS) in stem cell culture. However, current methods are time-consuming or require addition of exogenous substances to activate PRP, which have disadvantages in clinical applications. In this study, we developed a new method for PRP activation using a bead mill homogenizer and compared it with previous methods of PRP activation. PRP was prepared via a two-step centrifugation process and activated via calcium (Ca-PRP), freeze-thaw cycles (FT-PRP), or bead mill homogenizer processing (BM-PRP). Quantification of growth factors in PRP revealed that all forms of activated PRP released higher levels of platelet-derived growth factor-AB and transforming growth factor-β1 than those in platelet-poor plasma; however, BM-PRP resulted in significantly higher levels of growth factors than those from Ca-PRP and FT-PRP. Next, we analyzed the ability of the various forms of PRP to stimulate proliferation, migration, and differentiation of umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs). Our results showed that BM-PRP significantly increased proliferation and migration rates of UCB-MSCs while maintaining the phenotypical properties and stem cell abilities of MSCs. Therefore, the developed method could be suitable for PRP activation, and the BM-activated PRP could be an adequate replacement for FBS in stem cell culture.

Effect of mechanical activation on solid-state synthesis process of neodymium disilicate ceramic pigment

The effect of mechanical activation of precursors ground in a high-energy density stirred bead mill on the synthesis of Nd2Si2O7 powders was investigated. The reaction of precursors after the mechanical treatment at different milling time was analyzed by laser particles size analysis, thermogravimetry and differential thermal analysis (TG-DTA), X-ray diffraction (XRD) and scanning electron microscopy (SEM). The results reveal that the precursors without grinding and fired at 1200 °C cannot form the Nd2Si2O7 phase. Nd2Si2O7 can be formed at 986.9 °C when the precursors are ground for 3.0 h. To further clarify the effect of mechanical activation, two raw materials (i.e., SiO2 and Nd2O3) were pre-treated by different methods. The raw materials mixed and subsequently ground is conducive to decreasing the temperature of forming pure Nd2Si2O7 phase. The results indicate that the mechanical activation favors the promotion of the crystal growth of Nd2Si2O7. In addition, the color properties of the synthesized Nd2Si2O7 powders were also evaluated by reflection differential colorimetry. It is indicated that Nd2Si2O7 powders that possess a high-temperature stability can be used as a ceramic pigment.

The Effect of Ionic Strength and pH on the Electrostatic Stabilization of NanoRDX

In this work, 1,3,5-trinitroperhydro-1,3,5-triazine (RDX) with an average crystal size of 300 nm was prepared by bead milling to examine the effect of pH and ionic strength on the Zeta potential. The results showed that nanoRDX has no isoelectric point within the entire range studied (2<pH<11) . The maximum Zeta potential was reached under alkaline conditions of pH 11. The results indicate that the ionic strength, even at low concentrations of NaCl (0.002 mol/L), can increase the Zeta potential of the nanoRDX by 37 %. The Derjaguin-Landau and Verwey-Overbeek (DLVO) theory was used to evaluate the stabilization of nanoRDX at different ionic strengths. The Hamaker constant was determined to be 1.84×10-20 J and the total potential energy of interaction was computed at different electrolyte concentrations. The DLVO theory predicts that 300 nm RDX particles are stable at a low salt concentration of 0.002 mol/L and unstable at 0.1 mol/L. Turbidity test was conducted for nanoRDX dispersed in a solution of pH 11 and electrolyte concentration (NaCl) of 0.002 mol/L and compared to the nanoRDX dispersed only in water. The turbidity test qualitatively confirmed the results predicted by DLVO theory and Zeta potential measurements, showing that the nanoRDX dispersion was stabilized with the addition of electrolyte in an alkaline solution.

A microscale bacterial cell disruption technique as first step for automated and miniaturized process development

Abstract Cell disruption is crucial during recovery of biopharmaceuticals overexpressed in E. coli , which tend to be produced intracellularly as insoluble inclusion bodies. Miniaturized high-throughput systems can accelerate the laborious downstream protocol for such biopharmaceuticals and enable integrated process-development. A fast and robust cell disruption method reflecting the protein and impurity profile of homogenates obtained by large-scale methods is required for such an approach. We established a miniaturized bead mill for parallel mechanical cell disruption at the microscale. Its total protein and impurity release, protein pattern, and particle size distribution were compared to results from microscale enzymatic digestion and referred to laboratory-scale high-pressure homogenization. Bead mill disruption led to equivalent protein and impurity release as well as to the same particle size profile as the large-scale reference. In contrast, lysates obtained by enzymatic digestion contained only 30–47% of overall protein, 17% of dsDNA, and 7–10% of endotoxin compared to those obtained by high-pressure homogenization; also larger debris was present in lysates after enzymatic digestion. The established method is fast, efficient, robust and comparable to current large-scale standards, allowing for parallelization of experiments. Thus, it is the method of choice for rapid integrated process development at the microscale.

Energy consumption and water-soluble protein release by cell wall disruption of Nannochloropsis gaditana

Several cell disruption methods were tested on Nannochloropsis gaditana, to evaluate their efficiency in terms of cell disintegration, energy input and release of soluble proteins. High-pressure homogenization (HPH) and bead milling were the most efficient with >95% cell disintegration, ±50% (w/w) release of total proteins and low energy input (<0.5kWh.kg−1biomass). Enzymatic treatment required low energy input (<0.34kWh.kg−1biomass), but it only released ±35% protein (w/w). Pulsed Electric Field (PEF) was neither energy-efficient (10.44kWh.kg−1biomass) nor successful for protein release (only 10% proteins w/w) and cell disintegration. The release of proteins after applying HPH and bead milling always required less intensive operating conditions for cell disruption. The energy cost per unit of released protein ranged from 0.15–0.25 €.kgProtein−1 in case of HPH, and up to 2–20 €.kgProtein−1 in case of PEF.

Flow cytometry to estimate the cell disruption yield and biomass release of Chlorella sp. during bead milling

A number of visual, chemical and fluorescence-based methods are generally employed for monitoring of algae cell growth, culture health and biomass concentration. These methods are often time-consuming, demand destructive and high volume sampling. Rapid, efficient, cost-effective and automated methods which facilitate high-throughput and non-destructive sampling would highly benefit microalgae biotechnology. It is known in literature that with flow cytometry it is possible to monitor microalgae growth and microalgae culture health. Flow cytometry, however, has not been used to estimate biomass release and cell disruption yield. In this study with representative cultures of Chlorella sp., flow cytometry data were generated by a long pass filter (>670nm) and proved to be a promising technique to rapidly evaluate these parameters during cell disruption by bead milling. Both a laboratory and a commercial culture of Chlorella were bead milled. Prior to and during bead milling, biomass release was evaluated gravimetrically and the cell count was determined via hemocytometer manual counting and 3 flow cytometry methods: 1) direct event count of a certain population, 2) quadrant-upper right event count of a long pass filter (>670nm) and 3) a calculation based on the long pass filter data. The data of all methods were compared and correlated to gravimetric biomass release data. Manual counting resulted in an underestimation of the cell disruption yield as one of the Chlorella cultures manual counts did not agree with biomass release data. Good correlations for both cultures were found for cell disruption yield calculations based on flow cytometry data and gravimetric biomass release data. Flow cytometry is therefore an efficient analytical method to rapidly screen disruption yields during cell disruption in microalgae and can be a substitute for the time-consuming direct methods (e.g. gravimetric, manual counting) for estimating biomass release and cell disruption yield.

Improvement of Dissolution Rate and Stability in a Pirenoxine Ophthalmic Suspension by the Bead Mill Methods

Foreign matter sensation and blurred vision following instillation of ophthalmic suspension are often observed, and remaining of solid particle on cornea is related these side effects. In addition, low dispersion stability in the ophthalmic suspension affects the therapeutic effect. In this study, we have attempted to enhance the dissolution rate and stability of commercially available pirenoxine ophthalmic suspension (CA-pirenoxine eye drops), anti-cataract eye drops, by changes in particle size. Methylcellulose, zirconia beads (0.1 mm) and Micro Smash were used to mill the pirenoxine (bead mill method), and the distribution of particle size was changed to approximately 60-900 nm (nanodispersions) from 70 nm-3 μm (CA-pirenoxine eye drops). The dissolution rate of pirenoxine increased by the bead mill, and the dissolution rate constant in pirenoxine nanodispersions was 2.1-fold than that in CA-pirenoxine eye drops. Moreover, the dispersion stability in nanodispersions also significant higher in comparison with the CA-pirenoxine eye drops. The dispersion ratio in CA-pirenoxine eye drops and pirenoxine nanodispersions at 2 d after suspension was 48%, 99%, respectively. In conclusion, we showed that the dissolution rate and dispersion stability of CA-pirenoxine eye drops were enhanced by the bead mill method. These findings provide significant information that can be used in the design of ophthalmic suspension.

ПОЛУЧЕНИЕ ТОНКОДИСПЕРСНЫХ ПОРОШКОВ ФЕРРИТА НИКЕЛЯ NiFe2O4 МЕТОДОМ ВЫСОКОЭНЕРГЕТИЧЕСКОГО ПОМОЛА НА БИСЕРНОЙ МЕЛЬНИЦЕ ЗАМКНУТОГО КОНТУРА

ПОЛУЧЕНИЕ ТОНКОДИСПЕРСНЫХ ПОРОШКОВ ФЕРРИТА НИКЕЛЯ NiFe2O4 МЕТОДОМ ВЫСОКОЭНЕРГЕТИЧЕСКОГО ПОМОЛА НА БИСЕРНОЙ МЕЛЬНИЦЕ ЗАМКНУТОГО КОНТУРА