David Vetchý

University of Veterinary and Pharmaceutical Sciences Brno, Brünn, South Moravian, Czech Republic

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Publications (30)22.22 Total impact

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    ABSTRACT: Abstract Context: Liquisolid systems are modern formulations used to increase the bioavailability of poorly water-soluble drugs. Their preparation is based on the sorption of a drug in liquid state onto a carrier with a high adsorption capacity. The carrier particles are subsequently coated with material having a large surface area to form free-flowing powder. The main principle of bioavailability increasing is based on the presence of the dissolved drug, which is ready for immediate absorption in GI tract. Objective: Determination of capability of aluminometasilicate carrier Neusilin® US2 to adsorb different solvents. Materials and methods: The maximum amounts of polyethylene glycol 200 (PEG 200), polyethylene glycol 400 and propylene glycol (PG), which can be sorbed by Neusilin® US2, while maintaining an acceptable flowability of the powder mixture, were evaluated using determination of the flowable liquid retention potential. Results and discussion: From the evaluation of liquisolid powder mixtures, it could be observed that 1 g of Neusilin® US2 can retain up to 1.00 g of PG, 1.16 g of polyethylene glycol 400 and 1.48 g of PEG 200, while maintaining acceptable flowing properties. Conclusion: Large specific surface area in combination with a high absorption capacity makes Neusilin® US2 suitable carrier for liquisolid system preparation.
    Pharmaceutical Development and Technology 06/2014; · 1.33 Impact Factor
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    ABSTRACT: The aim of this experimental study was to optimize a preparation of microspheres from high viscosity chitosan by external ion gelation and to evaluate selected aspects of their preparation. For drug-free microparticles, the concentration of chitosan dispersions was chosen as a formulation variable; the position of instrument for a dispersion extrusion (horizontal vs. vertical) was evaluated as a process variable. On the basis of sphericity and equivalent diameter results, three different concentrations of chitosan dispersions were used for 5-aminosalicylic acid (5-ASA) encapsulation with the extrusion instrument in horizontal position, which was considered as the optimal. In consequent drug-loaded microparticle preparation, the influence of the concentration of chitosan dispersions and composition of hardening solution (10% sodium tripolyphosphate (TPP) vs. 10% TPP containing drug) was evaluated. In prepared 5-ASA microspheres it was found that the equivalent diameter increased with increasing chitosan concentration. In the case of sphericity, significant differences were not found. Samples prepared with the drug in both chitosan dispersion and hardening solution had a higher drug content, a smaller equivalent diameter and they showed a faster in vitro drug release in comparison with the samples prepared with the drug in chitosan dispersion only.
    Ceská a Slovenská farmacie: casopis Ceské farmaceutické spolecnosti a Slovenské farmaceutické spolecnosti 06/2014; 63(3):127-35.
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    ABSTRACT: Essential oil of the Siberian fir (Abies sibirica Ledeb.) ranks among the substances with potential use in prevention and treatment of oral candidiasis. Therefore, the aim of the study was the formulation, preparation and evaluation of an oral gel containing 0.3% of this essential oil. Carbopol 974P NF in 1% concentration was used as the gelling agent, some samples were additionally stabilized by an addition of polysorbate 80 (0.1-0.5%). Xylitol in concentrations of 10% or 20% was added with the aim to modify the taste properties of the gel. Following microscopic evaluation (mean oil droplet size, degree of dispersity) immediately after preparation and after 6-month storage, it has been found that the optimal concentration of polysorbate 80 is 0.3%. The results of the experiment also demonstrated that xylitol was not only an excipient adjusting the organoleptic properties of the preparation - its use enabled significant improvement of the quality parameters and stability.
    Ceská a Slovenská farmacie: casopis Ceské farmaceutické spolecnosti a Slovenské farmaceutické spolecnosti 06/2014; 63(3):113-9.
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    ABSTRACT: This study aimed to prepare high molecular weight chitosan blank and drug-loaded microparticles using 5-aminosalicylic acid (5-ASA) as the model active substance by an external ionic gelation. Formulation and process variables included the chitosan concentration and presence of drug in the polymer solution, and/or in hardening solution during the microparticles preparation. The effect of different preparation conditions on the properties of the microparticles was observed with a view to increase drug content in microparticles. For both types of microparticles (with and without the drug), it was found that their sphericity and equivalent diameter increased with increasing chitosan concentration. The drug content of drug-loaded microparticles was the highest in the case of the sample prepared from 1.75% chitosan dispersion, when the drug was present both in the chitosan dispersion and the hardening solution. Maximum six times higher drug content was achieved by change of the placement of 5-ASA during preparation (1.25% chitosan concentration). Keywords: microparticles external ionotropic gelation chitosan 5-ASA encapsulation efficiency.
    Ceská a Slovenská farmacie: casopis Ceské farmaceutické spolecnosti a Slovenské farmaceutické spolecnosti 04/2014; 63(2):75-83.
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    ABSTRACT: Texture analysis as a versatile tool for testing the inner structure of materials have been widely used. Though being also used in pharmaceutical industry, it has not been included in standard procedures for evaluation of drug dosage forms. The aim of this study is to measure the thickness of gel layer using texture analysis for the prediction of dissolution profile of very soluble drugs based on hydrophilic and hydrophilic-lipophilic matrix tablets. For the evaluation of the correlation between the thickness of the gel layer as an independent variable and the amount of a released drug as a dependent variable at given time intervals, the multivariate method of partial least squares – PLS-2 regression was used. For the prediction of dissolution characteristics of matrix tablets, a PLS-2 model validated by full cross-validation was developed. A PLS-2 model validated by full cross-validation was developed.
    Chemicke Listy 01/2014; 108(5):483-487. · 0.45 Impact Factor
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    ABSTRACT: Oral mucosa is an attractive region for the local and systemic application of many drugs. Oral mucoadhesive films are preferred for their prolonged time of residence, the improved bioavailability of the drug they contain, their painless application, their protection against lesions, and their nonirritating properties. This work was focused on preparation of nonmedicated carmellose-based films using both solvent casting and impregnation methods, respectively. Moreover, a modern approach to evaluation of mucoadhesive films applying analysis of texture and subsequent multivariate data analysis was used. In this experiment, puncture strength strongly correlated with tensile strength and could be used to obtain necessary information about the mechanical film characteristics in films prepared using both methods. Puncture work and tensile work were not correlated in films prepared using the solvent casting method, as increasing the amount of glycerol led to an increase in the puncture work in thinner films. All measured texture parameters in films prepared by impregnation were significantly smaller compared to films prepared by solvent casting. Moreover, a relationship between the amount of glycerol and film thickness was observed, and a greater recalculated tensile/puncture strength was needed for an increased thickness in films prepared by impregnation.
    BioMed Research International 01/2014; 2014:179568. · 2.71 Impact Factor
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    ABSTRACT: This experimental study describes the preparation of a veterinary medicated premix containing tetracycline hydrochloride for oral administration to aquatic animals. For the manufacture of the premix, commercially produced animal feed is used, which is intended for consumption in the form of pellets that were coated with a mixture of chlortetracycline hydrochloride and other excipients. Feed pellets were combined with a mixture of an active substance and excipients with a large specific surface (colloidal silica - Aerosil® 200) allowing an easy adhesion to the surface of the pellets, and a solid polymer with a low glass transition point (Eudragit® E) which ensures the formation of a hard coat. A mixture of these substances has been applied to the surface of the pellets either A) in the solid state simply by dry adhesion; B) by coating the pellets with the mixture and additional impregnation with ethanol; or C) the polymer was subsequently applied in solution. In the final stage, the pellets were heated in order to achieve the glass transition point of the polymer to create a solid and mechanically resistant coating. Coated pellets prepared by three methods described above are almost identical in their physical properties. With this technology it is possible to produce a feed mixture with a very low content of the active substance in situ without the need for a complex technological equipment.Keywords: medicated feed premix pellets impregnation adhesion fish.
    Ceská a Slovenská farmacie: casopis Ceské farmaceutické spolecnosti a Slovenské farmaceutické spolecnosti 01/2014; 63(5):213-216.
  • Acta Pharmaceutica 01/2014; in press. · 1.16 Impact Factor
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    ABSTRACT: Hypoglycemic episodes are a frequent and serious complication in both types of diabetes mellitus. The risk of hypoglycemic conditions can be managed by a coated pellet dosage form, which can release glucose in a delayed regime to achieve the maximum estimated effect of antidiabetics. The pellet cores, intended for coating with ethylcellulose, were prepared consisting of four osmotically active excipients: crosscarmellose (Ac-Di-Sol®), a mixture of microcrystalline cellulose and carmellose sodium (Avicel® RC 591), carboxymethyl starch sodium (Vivastar® P 5000) and macrogol 6000, respectively. The aim of this study was to increase the glucose content in the pellets to minimize their volume and to improve the administration to the patients. The content of glucose in the pellet cores was increased from 45 to 75 or 80%, respectively, for all compositions. All pellet samples had satisfactory mechanical and flow properties required for the coating process. The highest values of sphericity were achieved in the lower mean particle size sample containing 80% of glucose, 15% of Avicel® PH 101 and 5% of carboxymethyl starch sodium and the higher mean particle size sample containing 75% of glucose and 25% of Avicel® RC 591.Key words: hypoglycemia - delayed release - glucose.
    Ceská a Slovenská farmacie: casopis Ceské farmaceutické spolecnosti a Slovenské farmaceutické spolecnosti 01/2014; 63(5):206-212.
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    ABSTRACT: Mucoadhesive films represent the most developed medical form of buccal application. Despite the intense focus on buccal film-based systems, there are no standardized methods for their evaluation, which limits the possibility of comparison of obtained data and evaluation of the significance of influence of formulation and process variables on properties of resulting films. The used principal component analysis, together with a partial least squares regression provided an unique insight into the effects of in vitro parameters of mucoadhesive buccal films on their in vivo properties and into interdependencies among the studied variables. In the present study eight various mucoadhesive buccal films based on mucoadhesive polymers (carmellose, polyethylene oxide) were prepared using a solvent casting method or a method of impregnation, respectively. An ethylcelullose or hydrophobic blend of white beeswax and white petrolatum were used as a backing layer. The addition of polyethylene oxide prolonged the in vivo film residence time (from 53.24 ± 5.38 - 74.18 ± 5.13 min to 71.05 ± 3.15 - 98.12 ± 1.75 min), and even more when combined with an ethylcelullose backing layer (98.12 ± 1.75 min) and also improved the film's appearance. Tested non-woven textile shortened the in vivo film residence time (from 74.18 ± 5.13 - 98.12 ± 1.75 min to 53.24 ± 5.38 - 81.00 ± 8.47 min) and generally worsened the film's appearance. Mucoadhesive buccal films with a hydrophobic backing layer were associated with increased frequency of adverse effects.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 12/2013; · 3.15 Impact Factor
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    ABSTRACT: NIR spectroscopy together with multivariate data analysis were used to analyze the hydrates of diclofenac sodium prepared from the non-aqueous solvents tetrahydrofuran and methanol under standard laboratory conditions at 20 °C and relative humidity less than 60%. It was confirmed that the developed PLS regression model can monitor the process of formation of hydrates. It was also found that the hydrated form of diclofenac sodium arises during the preparation of the dosage form the using technology of impregnating the solid carrier by non-aqueous solvents, which resulted in reducing of the drug release rate from prepared tablets up to twice. NIR spectroscopy was confirmed as one of the effective PAT (Process Analytical Technology) methods. Keywords: process analytical technology method, PLS regression, NIR spectroscopy, hydrates, impregnation, diclofenac sodium.
    Ceská a Slovenská farmacie: casopis Ceské farmaceutické spolecnosti a Slovenské farmaceutické spolecnosti 12/2013; 62(6):259-63.
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    ABSTRACT: The solubility of weakly basic drugs within passage though GI tract leads to pH-dependent or even incomplete release of these drugs from extended release formulations and consequently to lower drug absorption and bioavailability. The aim of the study was to prepare and evaluate hydrophilic-lipophilic (hypromellose-montanglycol wax) matrix tablets ensuring the pH-independent delivery of the weakly basic drug verapamil-hydrochloride by an incorporation of three organic acidifiers (citric, fumaric, and itaconic acids) differing in their concentrations, pK a, and solubility. The dissolution studies were performed by the method of changing pH values, which better corresponded to the real conditions in the GI tract (2 h at pH 1.2 and then 10 h at pH 6.8). Within the same conditions, pH of matrix microenvironment was measured. To determine relationships between the above mentioned properties of acidifiers and the monitored effects (the amount of released drug and surface pH of gel layer in selected time intervals-360 and 480 min), the full factorial design method and partial least squares PLS-2 regression were used. The incorporation of the tested pH modifiers significantly increased the drug release rate from matrices. PLS-components explained 75% and 73% variation in the X- and Y-data, respectively. The obtained results indicated that the main crucial points (p < 0.01) were the concentration and strength of acidifier incorporated into the matrix. Contrary, the acid solubility surprisingly did not influence the selected effects except for the surface pH of gel layer in time 480 min.
    AAPS PharmSciTech 08/2013; · 1.58 Impact Factor
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    ABSTRACT: Oral mucosa is one of the specific surfaces of the human body, which is permanently exposed to external factors related with food intake, breathing and speaking processes, which can lead to the onset of some problems. Disorders of the oral mucosa are a group of diseases, affecting, in the course of life, the majority of the population. Many of the oral mucosa ailments are manifested by lesions. Recurrent aphthous stomatitis (RAS) is the most common of these diseases. Despite much clinical and research attention, its causes remain poorly understood and treatment is only symptomatic. RAS is reported to affect up to 25% of the population worldwide. Topical or systemic therapy (corticosteroids, antiseptics, anti-inflamatory drugs, immunomodulating agents, etc.) can be used for treatment of RAS-associated symptoms. In general, topical therapy should be preferred due to the smaller drug load of the organism. In both cases, the active substance has to be in suitable dosage form. Recently, besides the conventional ways of application (rinses), the main disadvantage of which is the short time of resistance in the oral cavity, mucoadhesive dosage forms are used. The aim of this article is to give a theoretical overview of the oral mucosa topic and its most frequent disease - recurrent aphthous stomatitis in terms of various types of the disease classification, diagnosis and therapy, and in terms of the usage of various types of active substances and medical forms.Keywords: oral mucosa recurrent aphthous stomatitis therapy mucoadhesive dosage forms.
    Ceská a Slovenská farmacie: casopis Ceské farmaceutické spolecnosti a Slovenské farmaceutické spolecnosti 01/2013; 62(1):12-18.
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    ABSTRACT: Mucoadhesion is a specific phenomenon of creating bonds during intimate contact between biological surfaces covered by a mucus layer and a mucoadhesive material. In recent years come to the forefront of interest in the pharmaceutical industry modern dosage forms based on this specific process. Films (discs, patches) composed of mucoadhesive polymers (cellulose derivatives, polyacrylates, polyoxyethylene, etc.) prepared by established methods (solvent casting, hot melt extrusion, etc.) could be perspective candidates for oral administration of many drugs due to their flexibility and comfortable use. In addition, they can circumvent the relatively short residence time of conventional oral dosage forms on the mucosa and provide a precisely measured drug dose to the application site. Moreover, they can also help to protect the wound surface, thus help to reduce pain and improve effectiveness of the therapy. The aim of this article is to give an overview about the principles of creation of mucoadhesive bonds and about novel dosage form - mucoadhesive films in terms of their composition, preparation and practical usage. Keywords: oral mucosa mucoadhesion principles mucoadhesive dosage forms films patches discs.
    Ceská a Slovenská farmacie: casopis Ceské farmaceutické spolecnosti a Slovenské farmaceutické spolecnosti 01/2013; 62(1):4-11.
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    ABSTRACT: Three cationic acrylic polymers, i. e. Eudragit® RL, Eudragit® RS and Eudragit® E 100, were evaluated for the purpose of microparticles preparation by the solvent evaporation method. The practically insoluble drug mirtazapine and the freely soluble drug tramadol hydrochloride were selected for encapsulation as extreme limits of drug solubility. The prepared microspheres were analyzed by optical microscopy, drug content analysis and dissolution test. It was observed that Eudragit® RL did not provide microparticles while Eudragit® RS and Eudragit® E 100 yielded spherical microparticles. Samples prepared with mirtazapine showed sustained drug release whereas tramadol hydrochloride samples released the drug in a pattern similar to the immediate release profile. Eudragit® RS was found to be superior to Eudragit® E 100 in its encapsulation efficiency, drug loading and smaller mean size of microparticles. Keywords: microparticles, solvent evaporation, sustained drug release, Eudragit®
    Ceská a Slovenská farmacie: casopis Ceské farmaceutické spolecnosti a Slovenské farmaceutické spolecnosti 01/2013; 62(6):249-254.
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    ABSTRACT: Modern wound treatment is based on the creation of moist wound environment which accelerates healing. For these purposes some devices and materials may be used, including carboxymethyl cellulose (CMC). Wound dressings currently available on the market contain CMC in the form of sodium salt. CMC in the acidic form has not been used in wound healing therapy yet. Likewise, there are only a few papers describing the acidic CMC preparation and properties, which are inter alia dependent on the degree of substitution (DS). Therefore, the aim of the study was to evaluate the influence of DS on absorptivity, which is one of the main features of dressings after application on the wound. Samples with DS from 0.1 to 0.45 were examined using five media: purified water, normal saline, buffer solution with pH 7.4, physiological buffer solution with pH 7.2, and solution A. Absorptivity was evaluated using a model wound created by us. It has been found that from the viewpoint of absorptivity the optimal DS of acidic CMC in the form of nonwoven fabric lies in the range from 0.25 to 0.35. Below or above these values the absorptivity is worse. Keywords: moist wound healing - carboxymethyl cellulose - degree of substitution - absorptivity.
    Ceská a Slovenská farmacie: casopis Ceské farmaceutické spolecnosti a Slovenské farmaceutické spolecnosti 01/2013; 62(2):89-94.
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    ABSTRACT: The aim of this study was to develop a multiple-unit dosage system that released model drug into the colon, and also to evaluate the efficiency of the dosage form in human volunteers. The developed system combines pH-, time- and biodegradable polymer-based mechanisms for drug targeting to the colon. Pellet cores containing caffeine as model drug and chitosan and microcrystalline cellulose as excipients were prepared by the extrusion/spheronization method. The prepared pellets were film coated with a pH-dependent polymer, Eudragit FS 30 D. The coating total weight gain was 28.83% (w/w). Thanks to the application of an outer enteric film and the multiple unit design of the dosage form, the variability in gastric emptying was overcome, and a colon-specific targeting relied on the reproducibility of a small intestinal transit time, which was reported to be 3 ± 1 hours. A biodegradable polymer in the pellet core, chitosan, ensured the site-specific release of the model drug due to its solubility at the lower pH of the colonic region and by its biodegradability from the bacteria present. The efficiency of the system was confirmed by the in vivo testing of human saliva. The time of the first appearance of caffeine into the saliva, T(lag), was used as a parameter to estimate the disintegration time of the pellets into the gastrointestinal tract. The caffeine appeared in the saliva within 6.95 ± 1.12 hours (T(lag)) in 9 volunteers. A comparison of the reported colon arrival times indicates that the developed system is applicable to colonic drug delivery.
    Drug Delivery 01/2012; 19(2):81-9. · 2.02 Impact Factor
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    ABSTRACT: Objective: To evaluate the effect of excipients disodium-edetate dihydrate and citric acid monohydrate on rate of antibiotic powder dissolution, particle size after dissolution and chemical stability of the product after reconstitution with water for injection and 5% glucose solution. Material and methods: The product containing excipients (Tazocin) was compared with generic products without excipients. Rate of dissolution was evaluated organoleptically and spectrophotometrically, particle size was determined microscopically after reconstitution and after 4 hours of standing at laboratory temperature and chemical stability was assessed by HPLC. Results: Tazocin dissolved significantly faster in both solvents compared to products without excipients (3-4 min versus 10-13 min). The limit for maximal number of particles larger than 25 mm in the reconstituted solution was not exceeded in any of the products either after using water for injection or after using 5% glucose, both after reconstitution and after 4 hours of standing at laboratory temperature. Nevertheless, only for Tazocin the number of unwanted larger particles decreased in time in both solvents. Disodium-edetate dihydrate and citric acid stabilized the dissolved particles of the active substance and prevented its transformation into the insoluble form, which results in lower number of unwanted large particles. Tazocin was more stable, but the stability was not significantly better than its generic products. Conclusions: Disodium-edetate dihydrate and citric acid monohydrate (and possibly the used method of lyophilisation) therefore have a positive effect on the preparation and properties of antibiotic solution for intravenous application.
    Klinicka mikrobiologie a infekcni lekarstvi 08/2011; 17(4):123-128.
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    ABSTRACT: Coated hard capsules are becoming increasingly important for a number of reasons such as administration of new active ingredients, oral vaccination, colon drug delivery or their use in preclinical and clinical trials. The independency of coating composition on capsules filling is the major advantage of this dosage form. In our study, two types of hard capsules (gelatin and hypromellose) were coated by non-aqueous solutions of Eudragit L and S 12.5, respectively, to achieve intestinal and distal ileic drug delivery. Gelatin hard capsules were coated with Eudragit film either directly or using hydroxypropyl cellulose sub-coating prior to the final coating. Hypromellose capsules were coated directly. Coated capsules were evaluated for coating thickness by optical microscope and for dissolution in different pH media. Gelatin capsules do not seem to be suitable for direct coating with Eudragit due to insufficient film adhesion to the smooth capsule surface and a brittleness of formed films. These problems can be solved by hydroxypropyl celullose interlayer application. Hypromellose hard capsules could be directly easily coated with both Eudragit solutions. Dissolution of caffeine from coated capsules showed the potency for enteric delivery in gelatin capsules with interlayer and Eudragit L film in 7.5 and 10.0% concentrations and in hypromellose capsules coated with EudragitL in 5-17.5% coating levels. Gelatine capsules with interlayer and 10% Eudragit S film and hypromellose capsules only with high coating level (20%) provided potential distal ileum targeting of incorporated drug. Eudragit S film sprayed onto hypromellose capsules surface was brittle especially in the junction zone between capsule cap and body. Better plasticity of Eudragit S coating could be probably achieved using a different plasticizer.
    Acta poloniae pharmaceutica 01/2010; 67(2):191-9. · 0.67 Impact Factor
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    ABSTRACT: Characteristics of inert starters in drug solution layering are important for successful active pellet formation. Four types of starters composed of sucrose or microcrystalline cellulose (MCC) or lactose and MCC were compared in our study. The active pellets were prepared using Wurster type apparatus. Yield and pellet quality parameters were determined. The highest yield (85.66-89.41%) was obtained for cores composed of MCC due to their insolubility in water (the drug solvent) and good mechanical properties. On the contrary, soluble and brittle sucrose cores dissolved partially during the process forming undesirable agglomerates and giving lower yield (76.2%). All pellet samples showed good flow properties and drug content from 82.4 to 94.5% of the theoretical drug amount.
    Drug Development and Industrial Pharmacy 08/2008; 34(12):1381-7. · 1.54 Impact Factor