Jarmila Oremusová

Stereoisomeric effect on antimicrobial activity of a series of quaternary ammonium salts

Two homologous series of diastereoisomeric racemic +/- cis and +/- trans-N,N-dimethyl-N-alkyl-2-benzoyloxycyclohexylmethylammonium bromides with the number of carbon atoms in the alkyl chain from six to twenty (m = 6,8 ... 20) were synthesised. Their structures have been elucidated by IR, UV and in some cases also with 1H and 13C NMR spectrometry. The title compounds were assayed for their antimicrobial activity on microorganisms S. aureus, E. coli and C. albicans. The highest antimicrobial activity was observed against S. aureus (log 1/MIC = 5.5 mol-1 dm3) and the lowest against E. coli (log 1/MIC = 4.5 mol-1 dm3). The +/- cis and +/- trans stereoisomers of all eight couples of diastereoisomeric compounds show differences in their physico-chemical characteristics (including partition coefficient and lipophilicity) which is also reflected in the different antimicrobial activity of these diastereoisomers.

Study of Micelle Properties and Thermodynamics of Micellization of the Benzethonium Chloride

Abstract The self-association of benzethonium chloride (BZCl) in aqueous solution has been analyzed as a function of temperature. The critical micelle concentration (CMC.), the degree of counterion binding (β) and thermodynamic parameters of micellization (molar Gibbs energy, enthalpy and entropy of micellization) were determined using six experimental methods (conductometry, potentiometry, UV spectrophotometry, spectrofluorimetry, NMR and densitometry) within the temperature range 20–50°C. All methods used gave very similar values for CMC. Changes in the thermodynamic parameters on micellization were determined by applying a mass action model.

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

Abstract 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.

Influence of Alcohols on Micellar and Release Balances of Cationic Surfactant – Carbethopendecinium Bromide (Septonex)

Abstract An objective of this work is analysis of influence of selected alcohols from the group of enhancers (ethanol, propan-1-ol, propan-2-ol) and humectants (ethane-1,2-diol, propane-1,2-diol and propane-1,2,3-triol) in the hydrogels containing carbethopendecinium bromide on their associative (critical micelle concentration and thermodynamic parameters) and release properties (pH, percentage of drug release and the release rate constant). The studied hydrogels contained constant amounts of the gel-creating basis (polymer chitosan – 2.5% w/w), drug carbethopendecinium bromide (Septonex) – 1.0% w/w and additive of alcohol in 5 and 10% w/w concentrations. Associative parameter – critical micelle concentration (CMC) was evaluated by conductometric measurements. The CMC significantly increased in the environment of alcohols in comparison with water solutions as many as 50 times, while concentration of alcohols ranged within W = 0–100% mass fractions. Micellization in the both environments was spontaneous (ΔGm < 0), and from the energetic point of view it was exothermic (ΔHm < 0). The additive of alcohols in hydrogels supported the drug relase from hydrogels. As the concentration of alcohols increased the mass percentage of the drug released from gel increased as well.

Micellization of Alkyl Trimethyl Ammonium Bromides in Aqueous Solutions–Part 1: Critical Micelle Concentration (CMC) and Ionization Degree

Abstract Conductivities of alkyl trimethyl ammonium bromides (alkyl = hexyl-, octyl-, decyl-, dodecyl-, tetradecyl-, hexadecyl-, and octadecyl-) in aqueous solutions were measured as afunction of molarity of surfactants, length of chain and temperature. Critical micelle concentrations (CMC) were estimated from the dependence of the specific conductivity on molarity of the surfactants. It was determined that the temperature dependence of CMC is U-shaped with aminimum shifting toward higher temperatures with decreasing chain length of the alkyl group. Quantities characterizing behaviors of surfactants below and above CMC were calculated and compared from conductivity measurements. Measured and calculated values of studied compounds were also compared with results of many other authors. The paper has the form of a minireview. It is a comparison of the presented experimental data of alkyltrimethylammonium bromides (C6–C18) with earlier works reported.

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

Abstract 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.

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.

Study of Surfactant (Benzyldimethylhexadecylammonium Chloride) Effect on Selected Properties of Hydrogels

Abstract This paper aims to provide analysis of the influences of concentration changes of the surfactant – benzyldimethylhexadecylammonium chloride in hydrogels on their liberation, rheological, association and solubility properties. The hydrogels contained constant amounts of the gel-creating basis (polymer chitosan – 2.5 % w/w), the drug (chlorhexidine dihydrochloride – 0.1 % w/w) and the surfactant, which was used as an enhancer (0.005 – 0.05 % w/w). The highest value of the released drug corresponded to the highest surfactant concentration in the hydrogel. Critical micelle concentration and thermodynamic parameters, molar Gibbs energy, enthalpy and entropy of micellization were calculated. A linear increase of the surfactant amounts in hydrogels caused a non-linear increase of the cloud point. The appearance of the surfactants associates in hydrogels influenced both their liberation and rheological properties.

Adsorption and release of terbinafine hydrochloride: Effects of adsorbents, additives, pH, and temperature

The paper describes results obtained within the study of factors affecting the process of an antifungal drug — terbinafine hydrochloride adsorption on two different adsorbents — charcoal and silicagel. The effects of the adsorbent area, pH value, temperature and additives (polymers — methyl cellulose and hydroxypropyl cellulose) were analyzed and their impact on the adsorption of terbinafine was derived. The increase of pH and temperature, and the presence of additives decreased the amount of terbinafine adsorbed on the adsorbents. Terbinafine is currently applied both perorally and topically. Hydrogels, i.e. compositions of a drug, additives and water, are, due to their advantageous properties, preferred topical dosage forms. Mass fraction of additives of 1 % to 4 % were studied from the view point of drug release. This study shows that both the sort and the concentration of polymers influence the drug release from hydrogels significantly.