[Show abstract][Hide abstract] ABSTRACT: Liquisolid systems are an innovative dosage form used for enhancing dissolution rate and improving in vivo bioavailability of poorly soluble drugs. These formulations require specific evaluation methods for their quality assurance (e.g., evaluation of angle of slide, contact angle, or water absorption ratio). The presented study is focused on the preparation, modern in vitro testing, and evaluation of differences of liquisolid systems containing varying amounts of a drug in liquid state (polyethylene glycol 400 solution of rosuvastatin) in relation to an aluminometasilicate carrier (Neusilin US2). Liquisolid powders used for the formulation of final tablets were prepared using two different methods: simple blending and spraying of drug solution onto a carrier in fluid bed equipment. The obtained results imply that the amount of liquid phase in relation to carrier material had an effect on the hardness, friability, and disintegration of tablets, as well as their height. The use of spraying technique enhanced flow properties of the prepared mixtures, increased hardness values, decreased friability, and improved homogeneity of the final dosage form.
BioMed Research International 06/2015; 2015. DOI:10.1155/2015/608435 · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Effective assessment and management of wound pain can facilitate both improvements in healing rates and overall quality of life. From a pharmacological perspective, topical application of nonsteroidal anti-inflammatory drugs in the form of film wound dressings may be a good choice. Thus, the aim of this work was to develop novel layered film wound dressings containing ibuprofen based on partially substituted fibrous sodium carboxymethylcellulose (nonwoven textile Hcel NaT). To this end, an innovative solvent casting method using a sequential coating technique has been applied. The concentration of ibuprofen which was incorporated as an acetone solution or as a suspension in a sodium carboxymethylcellulose dispersion was 0.5 mg/cm 2 and 1.0 mg/cm 2 of film. Results showed that developed films had adequate mechanical and swelling properties and an advantageous acidic surface pH for wound application. An in vitro drug release study implied that layered films retained the drug for a longer period of time and thus could minimize the frequency of changing the dressing. Films with suspended ibuprofen demonstrated higher drug content uniformity and superior in vitro drug release characteristics in comparison with ibuprofen incorporation as an acetone solution. Prepared films could be potential wound dressings for the effective treatment of wound pain in low exuding wounds.
BioMed Research International 05/2015; 2015. DOI:10.1155/2015/892671 · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Infectious stomatitis represents the most common oral cavity ailments. Current therapy is insufficiently effective because of the short residence time of topical liquid or semisolid medical formulations. An innovative application form based on bioadhesive polymers featuring prolonged residence time on the oral mucosa may be a solution to this challenge. This formulation consists of a mucoadhesive oral film with incorporated nanocomposite biomaterial that is able to release the drug directly at the target area. This study describes the unique approach of preparing mucoadhesive oral films from carmellose with incorporating a nanotechnologically modified clay mineral intercalated with chlorhexidine. The multivariate data analysis was employed to evaluate the influence of the formulation and process variables on the properties of the medical preparation. This evaluation was complemented by testing the antimicrobial and antimycotic activity of prepared films with the aim of finding the most suitable composition for clinical application. Generally, the best results were obtained with sample containing 20 mg of chlorhexidine diacetate carried by vermiculite, with carmellose in the form of nonwoven textile in its structure. In addition to its promising physicomechanical, chemical, and mucoadhesive properties, the formulation inhibited the growth of Staphylococcus and Candida; the effect was prolonged for tens of hours.
BioMed Research International 01/2015; 2015. DOI:10.1155/2015/580146 · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Flavonol (-)-epicatechin and its derived dimer procyanidin B2, present in high amounts in cocoa products, have been shown to exert beneficial effects on the heart and cardiovascular system; however, their mechanism of action has not been fully elucidated. We studied effects of (-)-epicatechin and procyanidin B2 on the oxidative phosphorylation of isolated rat heart mitochondria. (-)-Epicatechin and procyanidin B2 had stimulating effect (up to 30% compared to control) on substrate-driven (State 2) mitochondrial respiration. Their effect was dependent on the respiratory substrates used. (-)-Epicatechin at higher concentrations (from 0.27 µg/mL) significantly decreased (up to 15%) substrate- and ADP-driven (State 3) mitochondrial respiration in case of pyruvate and malate oxidation only. Procyanidin B2 (0.7-17.9 ng/mL) inhibited State 3 respiration rate up to 19%, the most profound effect being expressed with succinate as the substrate. (-)-Epicatechin at concentrations of 0.23 µg/mL and 0.46 µg/mL prevented loss of the cytochrome c from mitochondria when substrate was succinate, supporting the evidence of membrane stabilizing properties of this flavonol. Thus, both (-)-epicatechin and procyanidin B2 directly influenced mitochondrial functions and the observed effects could help to explain cardiometabolic risk reduction ascribed to the consumption of modest amounts of cocoa products.
[Show abstract][Hide abstract] ABSTRACT: Abstract The main objective of this study was to evaluate the influence of the formulation and process parameters on PLGA microparticles containing a practically insoluble model drug (ibuprofen) prepared by the o/w solvent evaporation method. Multivariate data analysis was used. The effects of altered stirring speed of a mechanical stirrer (600, 1000 rpm), emulsifier concentrations (PVA concentration 0.1 %, 1 %) and solvent selection (dichloromethane, ethyl acetate) on microparticle characteristics (encapsulation efficiency, drug loading, burst effect) were observed. It was found that with increased stirring speed, the PVA concentration or the use of ethyl acetate had a significantly negative effect on encapsulation efficiency. In addition, ethyl acetate had an adverse effect on the burst effect, while increased stirring speed had the opposite effect. Drug load was not affected by any particular variable, but rather by the interactions of evaluated variables.
Acta Pharmaceutica 12/2014; in press. DOI:10.2478/acph-2014-0032 · 1.03 Impact Factor
[Show abstract][Hide abstract] 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 07/2014; 2014(7):179568. DOI:10.1155/2014/179568 · 2.71 Impact Factor
[Show abstract][Hide abstract] 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; DOI:10.3109/10837450.2014.926921 · 1.34 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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. · 0.20 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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; 86(3). DOI:10.1016/j.ejpb.2013.12.002 · 4.25 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: Modern drugs with low bioavailability (such as hypolipidemics,
anti-inflammatory drugs, diuretics) present,
due to their poor water solubility a significant problem in
the formulation of solid dosage forms intended for systemic
absorption of the active substance. Several methods
have been described for improving solubility and hence
bioavailability of the mentioned drugs. One of the most
promising techniques is the incorporation of active substance
in liquid-solid systems. The systems are based on
the conversion of a liquid drug to a free-flowing compressible
dry powder, by sorption on suitable excipients – porous
carriers (alumsilicates, microcrystalline cellulose),
coated subsequently with a material of high absorption
capacity (SiO2). Liquid-solid systems exhibit some advantages
including low production costs, simple processing
and enhanced drug release. The main benefit is
high bioavailability of the liquid drug, caused by the large
surface area available for absorption without previous dissolution
of active substance. The review clarifies specific
aspects associated with the formulation of liquid-solid
systems – excipients and their properties (surface area,
adsorption capacity), methods of preparation, process variables
(solubility, liquid loading) and evaluation of the dosage
Chemicke Listy 05/2013; 107:681-687. · 0.20 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.