Association, Distribution, Liberation, and Rheological Balances of Alkyldimethylbenzylammonium Chlorides (C12-C16).

It is known that cationic surfactants have an antimicrobial effect and act as enhancers. This paper studies three cationic surfactants from the group of alkyldimethylbenzylammonium chlorides (dodecyl-, tetradecyl-, and hexadecyl). Interest is focused on the association of the surfactants with respect to temperature, partition balances and their influence on drug release, rheological properties, and the pH of hydrogels. The critical micelle concentrations (CMC) of the surfactants were estimated from dependencies of conductivity, density, spectrofluorimetry, and UV-VIS spectrophotometry on molarity in the temperature range of 25-50 °C. It was found that the temperature dependence of a CMC is U-shaped, with its minimum at 30 °C, and the CMC value decreases as the length of the chain increases. The pseudo-phase separation model was used for the calculation of various thermodynamic parameters, such as the Gibbs free energies (spontaneous process), enthalpies (exothermic process), and entropies of the micelles' formation, CMCs, and the degree of counterion binding. All thermodynamic parameters, as functions of the temperature, were estimated. It was found that partition coefficients increase as the length of the alkyl chain and the pH = (5.0-7.0) increase. The influences of surfactants, below and above the CMC, on drug (chlorhexidine dihydrochloride) release from hydrogels, rheological properties, and pH at 30 °C were studied. Also, the amounts of the released drug increase as the alkyl chains of the surfactants prolongate. The amounts of the released drug with the surfactant below the CMC are greater than that above the CMC. All hydrogels (regardless of the length of the alkyl chain) exhibit a non-Newtonian pseudo-plastic flow. The results obtained will be used in the formulation of the drug and surfactants into dosage forms.

Simultaneous formulation of terbinafine and salvia monoterpenes into chitosan hydrogel with testing biological activity of corresponding dialysates against C. albicans yeast.

This work was aimed at a progressive formulation of drugs into chitosan hydrogels. It was taken into consideration that a therapeutic effect of the drugs could be enhanced by a combination of natural compounds with chemical (synthetic) drugs. In this work, sage essential oil (SEO) bicyclic monoterpenes with antiflogistic, antiseptic, and antimycotic properties were combined with terbinafine (TB) having a strong antimycotic activity. Detail optimization of the hydrogel-drugs composition (SEO monoterpenes, TB, chitosan, and polysorbate 80 concentrations), based on permeation experiment and UV absorption/GC-MS analysis of permeated species (eucalyptol, camphor, borneol, thujone, TB) in dialysates, was made. Concerning the active drugs formulation, an optimum concentration of TB was set at the level providing maximum release of the SEO monoterpenes. In vitro activity of the dialysates from the optimized hydrogel was tested against Candida albicans showing that a minimum inhibition concentration was significantly exceeded. The experimental results revealed that the chitosan hydrogel was suitable for the simultaneous formulation of the natural drugs (SEO) with chemical drug (TB) resulting in the preparation with acceptable stability, required gel properties, and significant biological activity. Such preparation should be effective in an antimycotic dermal use.

Formulation of sage essential oil (Salvia officinalis, L.) monoterpenes into chitosan hydrogels and permeation study with GC-MS analysis.

This study deals with the formulation of natural drugs into hydrogels. For the first time, compounds from the sage essential oil were formulated into chitosan hydrogels. A sample preparation procedure for hydrophobic volatile analytes present in a hydrophilic water matrix along with an analytical method based on the gas chromatography coupled with the mass spectrometry (GC-MS) was developed and applied for the evaluation of the identity and quantity of essential oil components in the hydrogels and saline samples. The experimental results revealed that the chitosan hydrogels are suitable for the formulation of sage essential oil. The monoterpene release can be effectively controlled by both chitosan and caffeine concentration in the hydrogels. Permeation experiment, based on a hydrogel with the optimized composition [3.5% (w/w) sage essential oil, 2.0% (w/w) caffeine, 2.5% (w/w) chitosan and 0.1% (w/w) Tween-80] in donor compartment, saline solution in acceptor compartment, and semi-permeable cellophane membrane, demonstrated the useful permeation selectivity. Here, (according to lipophilicity) an enhanced permeation of the bicyclic monoterpenes with antiflogistic and antiseptic properties (eucalyptol, camphor and borneol) and, at the same time, suppressed permeation of toxic thujone (not exceeding its permitted applicable concentration) was observed. These properties highlight the pharmaceutical importance of the developed chitosan hydrogel formulating sage essential oil in the dermal applications.

[Formulation of benzethonium chloride into gels]. / Formulácia benzetóniumchloridu do gélov.

This study is focused on the preparation of gels with antimicrobial effects. A quaternary ammonium salt, benzethonium chloride, in a concentration of 0.01-0.5% (w/w) was employed as the drug. The humectant employed was propylene glycol in concentrations of 5% and 10% (w/w). Two types of polymers, chitosan and hydroxyethyl cellulose, in the same concentrations of 2.5% (w/w), were used for gel preparation. Finally the flow properties, rheological parameters and pH values of the gels were evaluated. Based on the obtained results, the samples of the gels prepared on the basis of chitosan and hydroxyethyl cellulose, which have the following optimum composition shown below, were found: 2,5% (w/w) CHIT + 0,5% (w/w) BZCl + 10% (w/w) PG; 2,5% (w/w) HEC + 0,5% (w/w) BZCl + 5% (w/w) PG.

[Influence of excipients on caffeine permeation from gels]. / Vplyv pomocných látok na permeáciu kofeínu z gélov.

UNLABELLED: The subject of this paper is a study of the influence of excipients on caffeine permeation from dermal semisolids drugs. Due to its advantageous properties, caffeine can be successfully used in dermal hydrogels. The choice of excipients from the group of humectants and cationic surfactants also plays an important role. The excipients should ensure long-term stability of hydrogels and the best permeation of the drug from gels. In particular, the influence of various excipients on caffeine permeation from gels and at the same time their influence on rheological properties of hydrogels were investigated. Based on the obtained results, the following optimal composition of caffeine gel was determined: 2.5 % chitosan + 0.1 % caffeine + 10 % propylenglycol + 0.1 % benzyldimethylhexadecylammonium chloride. KEYWORDS: caffeine hydrogels permeation rheological parameters.

[Influence of temperature and concentration of a surfactant on pharmaceutical availability]. / Vplyv teploty a koncentrácie tenzidu na farmaceutickú dostupnost lieciva.

This study aimed to analyze the influence of surfactant concentration and temperature on drug liberation from hydrogels and their flow properties. The surfactant benzethonium chloride (BZCl) was used in concentrations of 0.01, 0.1 and 0.5 % (w/w), while the drug chlorhexidine dihydrochloride (CHX) was used in a concentration of 0.1 % (w/w). Chitosan (CHIT) in 2.5 % (w/w) concentration was used as a gel-creating substance. The drug and surfactant liberation were evaluated within the temperature range of 25-40 °C. The largest amounts of both of them were liberated at the temperature of 40 °C. Through the concentration changes it was possible to obtain statistically significant differences (P < 0.05) between the liberation of CHX and BZCl. An analysis of the flow properties revealed that the character of the plastic system was not influenced by the changing concentration of the surfactant. The experimental results led to the conclusion that the optimum composition of the gel was as follows: 2.5 % (w/w) CHIT + 0.1 % (w/w) CHX + 0.01 % (w/w) BZCl.

[Evaluation of liberation of caffeine from dermal semisolids drugs]. / Hodnotenie liberácie kofeínu z dermálnych polotuhých liekov.

The paper deals with formulation of caffeine into dermal semisolid dosage forms - hydrogels. Caffeine was chosen as a model drug because its properties can be successfully used just in hydrogels. Protective and tranquilization effects can be used in the preparations for sunbathing, and its lipolytic and regenerative effect can be used for the treatment of androgenic alopecia or cellular bioprotection. The aim of the study was to investigate the influence of different concentrations of chitosan and caffeine on the liberation of gels. Besides, stability of the prepared samples was evaluated by means of the evaluation of their rheological parameters. Based on the obtained results, there was determined the optimal drug concentration - caffeine 0.2% (w/w) and also the gel forming substance - chitosan 2.3% (w/w).

[Influence of quaternary ammonium salt on liberation of drug with antiseptic effect]. / Vplyv kvartérnej amóniovej soli na liberáciu lieciva s antiseptickým úcinkom.

The paper evaluates the influence of three surfactants (carbetopendecinium halogenides) on the liberation of the drug chlorhexidine dihydrochloride (CHX) in 0.1% (w/w) from the dosage form-gel and also the flow properties of gels. The following tensides were evaluated: carbetopendecinium bromide (SB), carbetopendecinium chloride (SC), and carbetopendecinium iodide (SI). The tenside concentration was set under the critical micelle concentration. The biopolymer - chitosan (CHIT) in 2.5% (w/w) concentration was used as a gel creating substance. Based on the flow properties of the studied gels, it was found that the employed tensides exhibited no influence on the character of the system. The gels exhibited the character of plastic systems with time-independent flow. The drug liberation was evaluated at the temperatures of 20, 30 and 40 °C. Between the types of the tensides, the statistically significant differences (P < 0.05) were found as to the amount of the liberated CHX, which was reflected by the increased amount of the liberated drug. Based on the obtained results, it can be concluded that the most suitable was the SI tenside. From the gel with this tenside the greatest amount of CHX was liberated, which had the highest value of the liberation rate constant.

[Formulation of salvia-containing gels]. / Formulácia gélov s obsahom salvie lekárskej.

The trend during the past years is to prefer natural drugs to synthetically prepared medicines. Due to its important antiphlogistic, antiseptic and antihidrotic effects, Salvia officinalis L. has a wide use in medicine, pharmacy and cosmetics in various dosage forms. The aim of this research was the formulation of Salvia officinalis L. in the form of a tincture to hydrogels. Gels were parallelly prepared on the basis of the natural polymer chitosan and the synthetic polymer Carbopol 940. The evaluation was focused on the influence of the anionic polymer and the cationic polymer in different concentrations on hydrogel flow properties. Glycerol functioning as a humectant was used in various percentage ratios. On the basis of the determination of rheological parameters and flow curves lapses the most suitable hydrogel from the application point of view was selected.

Study of local anaesthetics--Part 196 formulation of the local anaesthetic heptacaine into hydrogel on the basis of chitosan.

The study aimed to formulate the local anaesthetic heptacaine into hydrogels on the basis of chitosan. The gel-creating compounds used included natural polymers --three different types of chitosan, namely those of a medium molecular weight, from the shells of shrimp, and from the bumblebees species Bombus terrestris. The prepared hydrogels were evaluated on the basis of their rheological properties and drug liberation. From the point of drug liberation and flow properties, the optimal gel composition was as follows: 0.1% heptacaine + 2% chitosan (medium molecular weight) + 0.2% carbaethopendecinium bromide.

[Study of local anaesthetics - part 200 choice of the optimal type of chitosan for the formulation of local anaesthetics of the carbamate type into hydrogels]. / Stúdium lokálnych anestetík - cast 200* Výber optimálneho typu chitosanu pre formuláciu lokálnych anestetík karbamátového typu do hydrogélov.

The aim of this examination was a study of hydrogels on the base of various types of the natural polymer chitosan with an assay of local anaesthetics of the carbamate type. The concentration of the gel-creating compound in hydrogels was 2.5%. The study included heptacainiumchloride (HEP), pentacainiumchloride (PEN) and carbisocainiumchloride (CAR). Evaluation was focused on the flow properties of prepared gels and the liberation of drugs from them. Based on the achieved results, the optimal type of biopolymer was determined: PEN - CHIT B, for CAR - CHIT C, while in the case of HEP it was found that chitosan is not suitable as a gel-creating base.

[Influence of membranes on alaptide permeation from hydrogels]. / Vplyv membrán na permeáciu alaptidu z hydrogélov.

The paper evaluates the liberation of alaptide from gels through various types of permeable membranes. The gels were prepared on the basis of three different polymers (3% chitosan; 2.5% hydroxypropyl cellulose; 3% hydroxyethyl cellulose) in different concentrations with additions of humectants (5 %; 15% propylene glycol and 10% glycerol) and the preserving agent, 0.3% Sepicide HBR with 1% alaptide, and finally without the drug. The permeation of the drug from gels into the acceptor solution was evaluated with the use of the following membranes: the hydrophilic membrane from Chemosvit, the chicken skin, the stripped snakeskin, and the wall of the small intestine. The measurements showed that the highest percentage of the drug penetrated through the small intestine, a smaller percentage through the chicken skin, and the smallest amount through the snakeskin. Rheological properties of the prepared hydrogels were evaluated as well. The pseudoplastic flow was only confirmed for the hydrogel prepared on the basis of hydroxypropyl cellulose. An utterly opposite situation was with the hydrogels prepared on the basis of chitosan and hydroxyethyl cellulose. They showed a significant thixotropic character and the degree of thixotropy increased with time. Based on the results of the pH measurement, the samples prepared on the basis of chitosan and hydroxypropyl cellulose have been shown to be inconvenient because they reached a lower pH and had a potential of causing skin irritation. The hydroxyethyl cellulose hydrogel matched the physiological values of skin pH even after 14 days since its preparation.

[Study of local anaesthetics--Part 194. Evaluation of carbopol hydrogels with lidocaine]. / Stúdium lokálnych anestetík--6ast' 194. Hodnotenie karbopolových hydrogélov s lidokaínom.

The objective of this article is to describe the formulation and evaluation of dermal semisolid drugs--carbopol hydrogels containing the solution of Bukofit, zinc chloride and the local anaesthetic lidocaine. The hydrogels were evaluated after 2, 7, 14 and 28 days after their preparation and stored at the temperature of 5 degrees C +/- 0.2 degrees C. All prepared hydrogels were found to be stable with respect to pH values and rheological parameters. It follows from the found rheological parameters and flow curves that all evaluated hydrogels belong to non-Newtonian thixotropic systems. The extensometric analyses revealed increased deformation values, indicating that the gels can be easily spread out over the mucous membrane which results in the increased ability of the drug to diffuse into it. Based on the results obtained, it can be concluded that the prepared hydrogels have appropriate technological parameters and therefore in the future they may become potential drugs for the treatment of various inflammations in the oral cavity.