Chitosan hydrogel with terbinafine--an evaluation of drug release.

The aim of this study was to evaluate rheological properties and release of terbinafine (an antifungal drug) from chitosan hydrogels, and test some additives as possible solvents, preservatives and potential chemical penetration enhancers. The release of terbinafine was better from hydrogel with glycerol (plastic flow), than that from hydrogel with propylene glycol (thixotropic flow), the presence of Tween 80 showed a negative influence on drug release from both types.

Influence of pre-systemic modifications on the drug performance.

Influences of technological and other pre-systemic modifications on the drug performance play a pivotal role in drug development and optimization. The paper evaluates these influences within a framework of the sensitivity theory. Deviations of the drug performance that were caused by modified pre-systemic parameters are predicted and compared with those obtained in vivo. A close correspondence between them demonstrates feasibility of the approach presented and its usability as an alternative or suplementary means of the in vitro-in vivo correlation analysis.

Indomethacin release in relation to the concentration of pharmaceutical excipients.

Indomethacin in vitro release was investigated in relation to the concentration of the pharmaceutical excipients, such as ethanol and propylene glycol. Drug release was studied from gels containing Sepigel 305 as a gelling agent. Not only the concentration of ethanol and propylene glycol influence the rate of indomethacin release, but also Sepigel 305 significantly increased the amount of indomethacin release.

Adsorption, partition and release balances of terbinafine hydrochloride, part I.

In this study the adsorption, partition and releasing balances of terbinafine hydrochloride have been studied. The adsorption isotherms of antifugal drug terbinafine hydrochloride (terbinafine), on the base of its adsorption from aqueous solutions on the surface of activated charcoal, were obtained in the temperature range of 25 to 45 degrees C used UV VIS spectrophotometric method. The experimental data have been analyzed by Freundlich and Langmuir equations to obtain parameters describing properly this adsorption process. The thermodynamic parameters (average change molar Gibbs energy--deltaadG0, enthalpy--deltaadH0 and entropy--deltaadS0) were calculated and compared. The partition coefficient of terbinafine hydrochloride in the system organic phase/water phase with different organic phases (n-butyalcohol, n-hexylalcohol and n-octylalcohol) using the "shake flask" method have been studied. The experimental partition coefficient of terbinafine increased from butylalcohol to octylacohol in the partitioning system. The influence of the concentration of polymer--hydroxy ethyl cellulose (HEC) (2-3%) used for preparation of the hydrogel (terbinafine-HEC-water), on terbinafine release has been studied. Both the concentrations of polymer and the drug had influence on the release process.

Effect of acceptor phosphate buffer pH value on indomethacin release.

This contribution investigated in vitro release of the antirheumatic drug indomethacin in relation to phosphate buffer pH in the acceptor part of the permeation apparatus. Drug release was studied from a hydrogel containing 3% of hydroxyethyl cellulose and from a cream. UV-spectroscopic evaluations were done after the preparation of the study drugs. Indomethacin release depends on the pH of the acceptor phosphate buffer, the higher pH value the better release.

Effect of beta-(1,3)-glucan on rheological properties and stability of topical formulations.

The paper deals with an effect of insoluble fungal beta-(1,3)-glucan on rheological properties of topical preparations. Two types of hydrogels (based on carbomer and polyacrylamide) and two types of hydrocreams (based on polysorbate 80/Span 80 and Brij 721TM/Brij 72) were prepared and investigated. The rheological properties of all these preparations were compared with the properties of placebos and they were measured after preparation and after 5 months of storage under different conditions: at 20 degrees C and 35 degrees C and after a triplicate freeze-thaw cycling process (-20 degrees C/+20 degrees C). In general it can be stated that with the exception of polyacrylamide hydrogel the beta-(1,3)-glucan presence increased the apparent viscosity of assessed preparations by approximately 10-20%. In the case of hydrocreams it was observed that the triplicate freeze-thaw cycling process increased the apparent viscosity of beta-(1,3)-glucan preparations by about 20-30%.

[Effect of humectants on pharmaceutical availability and rheological properties of cetirizine-containing hydrogels]. / Vplyv humektantov na farmaceutickú dostupnost a reologické vlastnosti hydrogélov s cetirizínom.

The paper is concerned with the formulation of the antihistamine cetirizine into hydrogels. The cellulose derivatives hydroxyethylcellulose (HEC) and methylcellulose (MC) were employed to prepare hydrogels. As auxiliary substances from the group of humectants are indispensable components of hydrogels, the paper examines their effect (glycerol--GL, propylene glycol--PG, and sorbitol--SO) on the rheological properties and pharmaceutical availability of cetirizine in its formulation into hyrogel. The obtained results show that from the viewpoint of dermal administration for cetirizine at this stage of research hydrogels of the following composition are optimal: 3% HEC + 15% GL and 2.5% MC + 10% SO.

[Effect of humectants on pharmaceutical availability and rheological properties of loratadine-containing hydrogels]. / Vplyv humektantov na farmaceutickú dostupnost a reologické vlastnosti hydrogélov s loratadínom.

The paper examines the formulation of the antihistamine loratadine into hydrogels, the polymers under evaluation being Carbopol 980 and Vivastar P 5000. As other pharmaceutical auxiliary substances from the group of humectants are an indispensable component of hydrogels, the paper evaluates their influence (glycerol--GL, propylene glycol--PG, and sorbitol--SO) on the structural viscosity and pH of hydrogels as well as pharmaceutical availability of loratadine. On the basis of the results of the study it can be concluded that from the viewpoint of dermal administration of loratadine the hydrogels of the following composition are optimal: 0.5% Carbopol 980 + 5% SO and 1.5% Vivastar P 5000 + 5% PG.

[Pre-formulation studies of the H1-antihistamine loratadine for a topical dosage form]. / Predformulacné stúdie H1--antihistaminika loratadínu do topickej liekovej formy.

The paper focuses on the formulation of the antihistamine loratadine for hydrogels. In the first stage of this study, the evaluated polymer for the preparation of hydrogels was Carbopol 980 of concentrations of 0.5, 0.8, and 1.0%. The paper aimed to determine the optimal concentration of Carbopol 980 in hydrogel formulation on the basis of the evaluation of the rheological properties and biological availability of loratadine from prepared hydrogels. The results of the study show 0.5% hydrogel of Carbopol 980 to be optimal for loratadine from the standpoint of topical administration.

[Preformulation studies of potential drug XIX M: partition coefficient]. / Predformulacné stúdie potenciálneho lieciva XIX M--rozdel'ovací koeficient.

The factors which markedly influence availability of the drug from the dosage form include also auxiliary substances, which are an inevitable component in the formulation of the drug. In the selection of auxiliary substances for a newly formulated drug, it is necessary to know that the drug is never a simple mixture of mutually independent ingredients, but a dynamic system in which various physical and chemical processes take place. The present paper aims to study the effect of auxiliary substances from the group of humectants with graded concentrations and the effect of the preservative on the partition coefficient of potential drug XIX M. Partition coefficient (P') was estimated in the system n-octanol/aqueous solution with graded concentrations of polyols. In these estimations, n-octanol simulated the horny layer, and the aqueous solution the base of the topical preparation. The auxiliary substances employed were polyols - glycerol, propylene glycol, and sorbitol in 5, 10, 15, and 20% concentrations and an antimicrobially effective solution of Ajatin (Solution benzododecinii bromati) in two concentrations of 0.01 and 0.1 wt %. It follows from the obtained results that the values of partition coefficient of potential drug XIX M are greatly influenced by auxiliary substances. The value of this parameter, and therefore also biological availability, depend not only on the sort of the polyol used and its concentration, but also on the concentration of the preservative employed, in this case Ajatin.

[Effect of polymer concentration on rheological properties of Carbopol 980 hydrogels containing trimecainium chloride]. / Vplyv koncentrácie polyméru na reologické vlastnosti hydrogélov Carbopolu 980 s obsahom trimekaíniumchloridu.

Rheological properties exert influence on the manufacturing processes, stability and usability of a dosage form as well as the biological availability of an active ingredient. The present paper examines the effect of Carbopol 980 concentration on rheological properties of hydrogels with and without trimecainium chloride for a period of 2, 7, and 14 days after their preparation. On the basis of an evaluation of the changes in structural viscosity in dependence on the period of measurement, it has been concluded that for formulation of trimecainium chloride to a dermal dosage form, Carbopol 980 concentrations of 0.5 and 1.2 % are suitable.

[The present and future of controlled transport of the drug into the organism]. / Súcasnost a budúcnost riadeného transportu lieciva do organizmu.

The problems of the systems of controlled (and thus also targeted) transport of the drug into the organism is one of the burning questions of contemporary biogalenics. Various more or less successful solutions were elaborated and applied, beginning with the retardette via the so-called intelligent hydrogels to various automatically controlled implants. Modem microfluidic intelligent biomicrosystems, composed of mutually interconnected microtanks, microjets, micropumps, or microcylinders, are very promising. A natural component of the complex biomicrosystem is a sensory subsystem for the collection of information from the bio-environment and a processor for the control of the process of drug supply to the organism. The present technologies of such Bio-Micro-Electro-Mechanical Systems (BioMEMSs) make it possible to revolutionize drug transport not only by facilitating precise dosing and long-term control of the immediate amount of the supplied drug on the basis of the current condition of the patient, but also to target the drug to the site of its pharmacological effect. Though at present there are still many unsolved problems, transition from laboratory conditions to clinical practice has started, and it is only a matter of five to ten years that intelligent BioMEMSs will gradually become a routinely used dosage microform. The paper briefly surveys the present state and the next development of intelligent systems of drug supply into the body of the patient, termed Intelligent Drug Delivery Systems, Intelligent DDSs, or briefly IDDSs.

[Examination of the stability of hydrogen peroxide solutions]. / Sledovanie stability roztokov peroxidu vodíka.

Reliable stabilization of the pharmaceutical preparation and the active ingredient remains one of the most important problems of world pharmacy because pharmaceutical preparations are not systems which are stable without limitation. The patient must receive a quality drug and that is why the question of stability is paid grest attention to not only in research and development, industrial manufacture, but also in distribution. The measure of stability is the expiration period. Diluted solution of hydrogen peroxide (3% solution) still belongs to the most widely used and at the same time the most easily accessible disinfectants. In practice it is common both in Slovakia and abroad. It is used in several concentrations. One of its most important disadvantages is its limited stability, which markedly decreases its expiration period. The present paper investigates the stability of hydrogen peroxide solutions of routinely used concentrations (3%, 6%, and 10%) without and with a stabilizing additive (phenacetin) prepared in the pharmacy and stored under different conditions for the period of their expected usability. The content of hydrogen peroxide was assayed by the pharmacopoeial method in 7-day time intervals. All concentrations of 3%, 6%, and 10% hydrogen peroxide were found to fulfil the conditions for stability in the period of time under study. Their concentration did not fall below the limit od 90% of the content of the active ingredient, and storage under decreased temperature proved to be more suitable. Storage of hydrogen peroxide in the light is inadmissible. When the conditions of storage are observed, the required therapeutic effect of hydrogen peroxide solution can be expected for the period of three months.

[A study of the stability of dioxopromethazine in aqueous solutions and ophthalmic instillation]. / Stúdium stability dioxoprometazínu vo vodných roztokoch a v ocnej instilácii metódou HPLC.

Dioxopromethazine began to be used in therapy as a modern antihistamine agent in the 1970s. A dioxopromethazine-containing ophthalmic instillation and a gel were employed until the end of the 1990s. The paper deals with the examination of the stability of the drug dioxopromethazine in aqueous solutions and the ophthalmic instillation Promefrin stored under different conditions. High-performance liquid chromatography with spectrophotometrical and electrochemical detection and HPLC connected on-line with mass spectrometry were employed for analysis. Dioxopromethazine in aqueous solutions and in ophthalmic instillations stored in direct sunlight was found not to be stable. However, the cover of the ophthalmic instillation, a brown-glass prescription bottle, and observation of storing conditions sufficiently protect the active ingredient from decomposition processes.

[Effect of pharmaceutical aids on physico-chemical indicators in solutions of substance XXII B]. / Vplyv pomocných látok na fyzikálno-chemické ukazovatele roztokov látky XXII B.

Within a study of optimization of auxiliary substances in the formulation of a hydrogel containing a potential local anaesthetic agent, substance XXII B, the paper evaluated the effect of a preservative (Ajatin) and humectants (glycerol, propylene glycol, sorbitol) on selected physicochemical indices, which included the partition coefficient, surface tension, and viscosity of the solutions of potential drug XXII B. On the basis of the statistical evaluation of the results, the optimal combination of auxiliary substances in this case seems to be Ajatin + glycerol.

[Rheologic properties of Vivastar P 5000 hydrogel]. / Stúdium reologických vlastností hydrogélov VIVASTARU P 5000.

Within the framework of pre-formulation studies, the paper evaluates the rheological properties of hydrogels whose gel-forming substance is a polymer supplied by the firm J. Rettenmaier & SöhneGMBH + CO. It is VIVASTAR P 5000, a modified derivate of carboxymethyl starch. The evaluation of rheological properties included hydrogels with 1.5, 2.0 and 2.5 w % of VIVASTAR P 5000. The highest viscosity was shown by the hydrogel with 2.0% concentration of the polymer. The system without and with the model drug with a local anaesthetic effect was thixotropic. From the viewpoint of topical administration, VIVASTAR P 5000 in 2.0% is optimal for hydrogel formulation.

[Liberation of potential local anesthetics from colloidal dispersions]. / Uvolnovanie potenciálnych lokálnych anestetík z koloidných disperzií.

Evaluation of pharmaceutical availability of drugs from topical preparations is usually aimed to evaluate the capability of the dosage form to release the drug for its therapeutic action. Permeation cells have been used for this purpose, employing solid membranes including cellophane. Within a study of phenylcarbamic acid derivatives with local anaesthetic effect, the present paper evaluates the dosage form for topical administration containing potential drug XIX M, the chemical name N-[2-(2-heptyloxyphenylcarbamoyloxy)-ethyl]-morpholinium chloride and potential drug XXII B, the chemical name N-[2-(2-octyloxyphenylcarbamoyloxy)-ethyl]-dimethylammonium chloride. The selected auxiliary substance in the formulation of the dosage form was a cellulose derivative--methylcellulose in increasing concentrations from 0.5 to 1.5%. On the basis of the obtained results it can be stated that the examined polymer methylcellulose with increasing concentration decelerated the release of both potential drugs approximately in the same way and that it can be used in practice to prolong the local anaesthetic effect.

Influence of hydrogel bases on liberation rate and structural viscosity of potential drug XX Z.

Influences of cellulose derivatives (with and without additives of humectants) on two parameters, namely the liberation of the potential local anaesthetic XX Z and the structural viscosity of preparations were compared. The aim was to select a suitable base for topic application of the substance XX Z, chemically pyrrolidinoethylester of 3-heptyloxyphenylcarbamic acid. The rate of release of the substance XX Z from 2.5% methylcellulose base was higher then from 2% hydroxyethylcellulose base, and in both cases it was reduced after addition of humectants. It is concluded that among bases with additives of humectants is, for topic applications, more suitable the hydroxyethylcellulose base then methylcellulose base.

A study of local anaesthetics. Part 148. Influence of auxiliary substances on the surface tension, distribution coefficient and pharmaceutical availability from solutions of the potential drug VII.

The influence of auxiliary substances of the polyol group (glycerol, propylene glycol, sorbitol) and of their concentration (5, 10, 15 and 20% by weight) upon surface tension, distribution coefficient and pharmaceutical availability from solutions of the potential drug VII, viz., N-[2-(2-propoxyphenylcarbamoyloxy)-ethyl] piperidinium chloride was studied. The substances were applied as hydrogel humectants. It was found that their influence on the surface tension, distribution coefficient and pharmaceutical availability from solutions of the potential drug VII depended on the type as well as concentration of the auxiliary substance. From the viewpoints of use in formulations of the drug form, sorbitol used at 5 and 10% concentrations represented the optimum.