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Dive into the research topics where Zdenka Šklubalová is active.

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Featured researches published by Zdenka Šklubalová.


Drug Development and Industrial Pharmacy | 2006

Study of Eye Drops Dispensing and Dose Variability by Using Plastic Dropper Tips

Zdenka Šklubalová; Zdenek Zatloukal

ABSTRACT The application of eye drops from flexible dropper bottles fitted with different types of dropper tips is associated with the high variability of eye drop weights. The aim of this report was to investigate the simultaneous effect of three factors influencing the mean weight of drops dispensing from two plastic dropper tips. Using a designed experiment (Box-Behnken), the effect of the concentration of benzalkonium chloride solutions (BAC) in the range of 0–0.02%, the dispensing angle from 90° to 30° from horizontal, and the residual volume of liquid in the dropper bottle from 4 to 10 mL on the mean drop weights were examined. The significant effect of the increase in BAC concentration resulted in a linear decrease in drop weights for both of the dropper tips investigated. The significant effect of the dispensing angle was influenced by the dropper tip design. For the dropper tip A, the effect of the dropper tip tilt was described by the quadratic equation with a minimum, which corresponded to the dispensing angle equal to that of 48° from horizontal. Below this angle, the increase in drop weights occurred due to the drop formation from the wetted external surface of the tip orifice. The linear decrease in drop weights in response to the decrease in dispensing angle was detected for the dropper tip B. The regression equations and the contour line plots obtained allowed the drop weights to be estimated for the actual combinations of both the BAC concentration and the dispensing angle. The effect of the residual volume was found to be non-significant. Based on the formula of Tates law, the direct proportion between surface tension of a solution and the radius of the effective perimeter of a dropper tip can be used to estimate the theoretical maximal weight of drops at the dispensing angle of 90°. Using the stalagmometric values of surface tension of the BAC solutions, the maximal drop weights were estimated for both of the dropper tips investigated. A comparison between the theoretical and the experimentally measured drop weights enabled the dropper tips behavior to be discussed by using Harkins and Brown correction factor F. The F-value of 0.74 noted for the dropper tip A differed from that of stalagmometer F-value (0.61) indicating a deviation from the simple drop formation process in answer to more complicated design of the dropper tip A. On the other hand, the F-value of 0.6 observed for the dropper tip B demonstrated the better consistency with stalagmometry. As a result, the dropper tip B with the linear decrease of drop weights in response to the increased concentration of BAC and the decreased dispensing angle without the adverse external drop formation could be recommended in real drop dispensing.


Journal of Automated Methods & Management in Chemistry | 2015

Development of a Gradient HPLC Method for the Simultaneous Determination of Sotalol and Sorbate in Oral Liquid Preparations Using Solid Core Stationary Phase

Ludmila Matysová; Oxana Zahálková; Sylva Klovrzova; Zdenka Šklubalová; Petr Solich; Lukáš Zahálka

A selective and sensitive gradient HPLC-UV method for quantification of sotalol hydrochloride and potassium sorbate in five types of oral liquid preparations was developed and fully validated. The separation of an active substance sotalol hydrochloride, potassium sorbate (antimicrobial agent), and other substances (for taste and smell correction, etc.) was performed using an Ascentis Express C18 (100 × 4.6 mm, particles 2.7 μm) solid core HPLC column. Linear gradient elution mode with a flow rate of 1.3 mL min−1 was used, and the injection volume was 5 µL. The UV/Vis absorbance detector was set to a wavelength of 237 nm, and the column oven was conditioned at 25°C. A sodium dihydrogen phosphate dihydrate solution (pH 2.5; 17.7 mM) was used as the mobile phase buffer. The total analysis time was 4.5 min (+2.5 min for reequilibration). The method was successfully employed in a stability evaluation of the developed formulations, which are now already being used in the therapy of arrhythmias in pediatric patients; the method is also suitable for general quality control, that is, not only just for extemporaneous preparations containing the mentioned substances.


Particulate Science and Technology | 2012

Effect of Orifice Geometry on Particle Discharge Rate for a Flat-Bottomed, Cylindrical Hopper

Zdenek Zatloukal; Zdenka Šklubalová

In this work, the influence of the geometry of a cylindrical flat-bottomed hopper orifice on the mass discharge rate of six free-flowable powder excipients with the size fraction 0.050–0.063 cm was investigated. Sixteen combinations of the orifice diameter and the height were used. The influence of the orifice diameter was described by the flow equation. However, the discharge rate was also affected by the orifice height. The influence of the orifice geometry on the powder discharge rate was indirectly studied by the parameters of the Beverloo equation. The value of the coefficient of determination and the precision of the discharge rate prediction were the basic criteria. The mean relative differences between the actual discharge rate at the combination of the orifice diameter and its height and the average discharge rate allowed a direct study of the effect of the orifice geometry. The complex nature of the orifice height impact on the powder discharge rate through the hopper opening has been determined. Based on the results, the orifice diameter of 0.8 cm with the height less than 0.8 cm is recommended. The method of powder flow evaluation proposed here can be used in testing of other powder fractions in future.


Particulate Science and Technology | 2008

Drained Angle of Free-Flowable Powders

Zdenek Zatloukal; Zdenka Šklubalová

The measurement of the angle of repose is a conventional method for estimation of powder flowability. This method is known to have lower reproducibility of results when greater angles of repose are obtained, in particular in the case of cohesive powders. The flowability of free-flowable powders can also be characterized by discharging from a hopper. In a cylindrical flat-bottomed hopper having a central circular orifice, a residual amount of powder remains in the hopper at the end of the discharging procedure. In this work, the size fractions of sodium chloride, sodium citrate, and potassium citrate in the range 0.0315–0.0600 cm were characterized with the bulk density and the mass discharge rate through 0.6–1.2 cm orifices of the cylindrical stainless steel hopper. The mass of the residual powder has been found to be indirectly proportional to the powder discharge rate. A method of the indirect estimation of the drained angle was proposed. The derived equation uses the mass of the residual powder, the powder bulk density, the inner diameter of the hopper, and the diameter of the hopper orifice as the independent variables. In the studied range of variable values, the experimentally obtained drained angles showed significant negative correlation with the mass discharge rate and the volume discharge rate of test powders, while no correlation was found between the drained angle and the mass discharge coefficient of the Beverloo equation. In order to measure the drained angle in the cylindrical hopper having an inner diameter of 4 cm, an orifice diameter equal to 1.0 cm was optimal. Filling of the powder into a hopper in conformity with the standard conditions of bulk density measuring in a graduated cylinder is the basic presumption. Since the drained angle follows the relief of bulk powder during discharge from the cylindrical hopper, it thus describes the powder flowability more comprehensively than the angle of repose to the horizontal. Good reproducibility of results follows the 3-D indirect estimation of the drained angle as well. In order to avoid any residue of powders in the conical hopper at the end of the discharging operation, the wall angle could be larger than the drained angle of the powder in the cylindrical hopper. This is typical for the mass flow of size fractions of free-flowable powders, the drained angles of which are approximately two times greater than their angles of repose.


Pharmaceutical Development and Technology | 2007

Sterilized ophthalmic hydrogels with hydroxypropyl methylcellulose: determination and mathematical treatment of flow properties.

Zdenek Zatloukal; Zdenka Šklubalová

In this article, the influence of electrolytes on the viscosity of sterilized hydrogels containing 60 g/L of hydroxypropyl methylcellulose (HPMC 4000) was investigated. The electrolytes mostly used in ophthalmics were sodium chloride, pilocarpine hydrochloride, atropine sulphate, and scopolamine hydrobromide. The hydrogels were prepared by using stationary method with a long period of storage in the refrigerator following the steam sterilization. Cone and plate rotational viscometry readings were modeled by using the three-parameter power law, which was validated by regression coefficients in the range of 0.9980–0.9999. In comparison to the hydrogel without additives, the significant decrease in viscosity was observed in the presence of pilocarpine hydrochloride in concentrations of 10 g/L and 30 g/L. On the other hand, the addition of sodium chloride, atropine sulphate, and scopolamine hydrobromide resulted in increasing of viscosity of hydrogels. The differences were nonsignificant when the single-point rheological characteristic, the apparent viscosity η100, was evaluated, in contrast to using the area under rheogram (AUR) data when the significant effect of sodium chloride could be proved. Therefore, in conclusion, the multipoint rheological AUR data could be recommended. In the investigation of gentle plastic rheograms, nevertheless, the allocation of the lower limit of the integration to yield value is emphasized, which prevents the integration of a negative portion of flow curve and, consequently, the lower values of AUR to be obtained.


Pharmaceutical Development and Technology | 2018

The influence of stevia on the flow, shear and compression behavior of sorbitol, a pharmaceutical excipient for direct compression

Hana Hurychová; Pavel Ondrejček; Zdenka Šklubalová; Barbora Vraníková; Tomáš Svěrák

Abstract Good flow and compaction properties are necessary for the manipulation of particulate material in the pharmaceutical industry. The influence of the addition of an alternative sweetener, rebaudioside A, in a concentration 0.2% w/w and 0.5% w/w on the flow, shear and compaction properties of sorbitol for direct compaction, Merisorb® 200, was investigated in this work. Rebaudioside A worsened the flow properties of sorbitol: the Hausner ratio, the compressibility index and the mass flow rate through the aperture of a model hopper. Using a Jenike shear cell revealed a significant increase in cohesion leading to the decrease of the flow function; moreover, the addition of rebaudioside A increased the total energy for compression of tablets and plasticity estimated by the force–displacement method. Finally, the tablets showed a higher tensile strength and needed longer time to disintegrate compared to the tablets made of sorbitol itself. In view of the results for the free-flowable excipient, sorbitol, the effects of stevia even for a 0.2% w/w concentration have to be carefully considered, particularly whenever used in pharmaceutical formulations of poor flow properties.


Journal of Pharmaceutical Innovation | 2018

Fractal Aspects of Static and Dynamic Flow Properties of Pharmaceutical Excipients

Hana Hurychová; Martin Kuentz; Zdenka Šklubalová

PurposeCharacterisation of powder flow is important for pharmaceutical processing and manufacturing. This work aims at a better understanding of how fractal particle and bulk properties affect the static and dynamic flow of excipients.MethodsTraditional methods of flowability testing, e.g. the angle of repose or the flow through an orifice, were complemented by avalanching in a rotational drum. Dynamic image analysis provided a fractal contour line dimension of the powder bulk in the drum (bDF). This was compared to the contour line fractal dimension of particles (pDF) as obtained from the box-counting method. Avalanche testing was able to measure also cohesive materials that were otherwise difficult or not measurable at all using the classical methods.ResultsThe values of the avalanche energy were in good agreement with the different flow properties of the samples. These flow properties showed good correlations with bDF in that poor flow properties were associated with a more rugged contour line of the bulk and hence higher bDF.ConclusionsInterestingly, there was no correlation observed between pDF and bDF, which may suggest that a distinct bulk structure typically emerges from the particles under dynamic flow. Future research should further clarify how fractal powder aspects affect pharmaceutical manufacturing processes.


Pharmaceutical Development and Technology | 2008

Indentation Test for Free-Flowable Powder Excipients

Zdenek Zatloukal; Zdenka Šklubalová

Indentation of a sphere into nonconsolidated powder excipients is a suitable complementary method for the evaluation of flow properties of the free-flowable noncohesive powders. To use the standard penetrometry method to indentation of nonconsolidated powder layer by a glass sphere of 16 mm in diameter, the suitable geometry of the measurement container is required to prevent undesirable moving in a direction opposite to that in which the indenting sphere moves. Thus, the powder indentation by a sphere seems to be similar to indentation by the Brinell hardness tester. In this work, the depth of indentation was measured for five pharmaceutical powder excipients: sodium chloride, sodium citrate, potassium citrate, sorbitol, and boric acid with the three size fractions in the range of 0.315–0.630 mm. To express powder flowability, the uniform mass and/or volume flow rate from the 10-mm cylindrical outlet of the cylindrical testing hopper was used. The relationships between the powder flow rate and its bulk density and/or the different characteristics of indentation were modeled by using linear regression. Out of the indentation characteristics, the mass of indentation calculated as the multiple of the volume of indentation and the powder bulk density could be recommended to estimate the powder mass flow rate due to the linear regression with the coefficient of determination equal to 0.973 and the accuracy of 4.3%. In conclusion, the indentation by the sphere could be recommended as a quick simple method for the comparison of flow properties of the nonconsolidated, noncohesive powder excipients.


Pharmaceutical Development and Technology | 2008

Optimization of regression equation for prediction of viscosity of aqueous solutions of the cellulose derivatives.

Zdenka Šklubalová; Zdenek Zatloukal

Commercially, cellulose products are designated with viscosity grade measured at 2% w/v concentration in water at 20°C using an Ubbelohde viscometer. To represent viscosity/concentration curves, linear function of the eighth root of dynamic viscosity and the concentration is generally used. In this work, the influence on viscosity of aqueous solutions of methylcellulose 400 and hypromellose 4000 by temperature and polymer concentration was modelled using an empirically proposed multiple linear regression in which the transformation of viscosity by logarithm, the reciprocal value of the absolute temperature, and the concentration by square root was recommended. Due to this, the viscosity of both cellulose derivatives investigated could be predicted simultaneously with the mean difference between the observed data and the ones estimated equal to 16.2%. Expanding the linear regression with the linear interaction between logarithm of the polymer viscosity grade and square root of the polymer concentration, the precision of the viscosity prediction increased to the acceptable level of 4.1%. Other interactions between the studied variables did not provide significantly better results. The optimized regression equation enabled the prediction of kinematic, dynamic, relative, and specific viscosity of the aqueous solutions of cellulose derivatives. The dimensionless relative viscosity could be recommended because it takes into account the water viscosity at the same experimental temperature. Selecting viscosity grade of the cellulose derivative and temperature of measurement, the partial regression equations were obtained from which the relative viscosity could be determined as the function of the polymer concentration with the precision in range of 1.3–4.7%.


European Journal of Hospital Pharmacy-Science and Practice | 2018

Furosemide ethanol-free oral solutions for paediatric use: formulation, HPLC method and stability study

Lukáš Zahálka; Sylva Klovrzova; Ludmila Matysová; Zdenka Šklubalová; Petr Solich

Background Oral liquid solutions of the diuretic active ingredient furosemide (FUR) marketed across Europe do not comply with recent requirements for paediatric preparation owing to their ethanol content and, moreover, in some countries only tablet or injection dosage forms of furosemide are available. Objectives To formulate extemporaneous paediatric ethanol-free solutions of FUR (2 mg/mL) with suitable solubility in the aqueous vehicle and an acceptable taste and to evaluate their stability under two different storage conditions during a 9-month study period. Methods Our work presents two developed formulations of FUR ethanol-free paediatric oral solutions 2 mg/mL for easy extemporaneous compounding in a pharmacy. FUR solubility avoiding the use of ethanol was achieved using sodium hydroxide (formulation F1) or disodium hydrogen phosphate dodecahydrate (formulation F2). The preparations were stored at 25°C±3°C or at 40°C±0.5°C and protected from light. For FUR and preservative, methylparaben (MP), a stability assay was conducted by a high-performance liquid chromatography validated method and determination of pH stability. Results The remaining FUR concentration was >90% of the initial concentration after 270 days in both formulations at both storage conditions, 25°C and 40°C. The concentration of MP decreased significantly in the formulation F2 stored at 40°C. Conclusions Both formulations were stable when stored at room temperature for up to 9 months; formulation F1 was stable even at 40°C. MP used as an antimicrobial agent fully satisfied the recommended criteria for preservative efficacy in oral preparations according to the European Pharmacopoeia 9.0 (5.1.3).

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Sylva Klovrzova

Charles University in Prague

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Zdenek Zatloukal

Charles University in Prague

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Ludmila Matysová

Charles University in Prague

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Lukáš Zahálka

Charles University in Prague

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Petr Solich

Charles University in Prague

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Hana Hurychová

Charles University in Prague

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Oxana Zahálková

Charles University in Prague

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Barbora Vraníková

Charles University in Prague

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K Kučerová

Charles University in Prague

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