Influence of selected tensides on the hydrocortisone concentration equilibrium balance in micelles and the dispersing center.

The degree of hydrocortisone binding, was investigated by means of equilibrium dialysis in the presence of 1% or 3% micellar solutions of polysorbate 20 and 80. Stabilization of the concentration equilibrium was found in all the cases investigated. The degree of hydrocortisone binding in micelles depends on the concentration and type of tenside used.

Influence of tensides on the release of medical agents from hydrophilic gels, part 2: The influence of selected tensides on hydrocortisone release from xerogels.

With the increase of polysorbates 20 and 21 concentration in xerogels, in the presence of 1,2-propylene glycol and PEG 200, hydrocortisone half-release periods from these preparations become longer while the half-release periods for polysorbate 80 and propylene glycol, and polysorbate 21 and PEG 200 are proportionally shortened. The concentration of tensides has no significant impact on the half-release periods of hydrocortisone with polysorbate 81 added to xerogels in the presence of propylene glycol and polysorbate 20 and 80 with PEG 200.

Studies on gynaecological hydrophilic lactic acid preparations, part 6: use of Eudragit E-100 as lactic acid carrier in intravaginal tablets.

Hydrophilic intravaginal tablets based on methylcellulose and containing lactic acid component with Eudragit E-100 undergo swelling in standard conditions. A high flow-limit of the gel that originates from the tablets as well as its dynamic viscosity should allow for the durable dosage form in the vagina. By choosing a 1:1 ratio of lactic acid to Eudragit E-100, it is possible to obtain tablets disintegrating into a gelform at physiological range of 3.8-4.4. An increase in the amount of lactic acid in the complex in relation to the polymer up to 2:1 and 3:1 ratios results in gels with a lower pH. These gels possess an acid reserve that might be ableto neutralise the excess of alkali present in severe vaginal infections.

Studies on gynaecological hydrophilic lactic acid preparations. Part 5: The use of Eudragit E-100 as lactic acid carrier in intravaginal tablets.

Intravaginal tablets based on hydrophilic methylcellulose and containing lactic acid complexed with Eudragit E-100 undergo deformation under standard conditions. The high flow--limit of gel originating from the tablets as well as its dynamic viscosity should enable durability of this dosage form on the vaginal mucosa. By selecting either 1 : 1 or 2 : 1 ratios of lactic acid to Eudragit E-100 it is possible to obtain tablets that disintegrate into a gelform at pH 3.8-4.4, i.e. the pH remains within the physiological range. Increasing the amount of lactic acid in the complex in relation to the polymer to a 4:1 ratio results in gels with a lower pH while possessing an acid reserve that can neutralize the excess of alkali present in severe vaginal infections.

Influence of some polysorbates on hydrocortisone release from hydrophilic gels considered as two-compartment models.

Hydrocortisone release from hydrogels containing of 1% and 3% polysorbate 20 or polysorbate 80, in the presence of 1,2-propylene glycol or PEG 200 has two stages. In the first one the release rates are higher than those of the second stage. Half-release times in the first stage are in the range 0.31 h to 0.48 h and in the second stage 16.65 h to 23.22 h. Hydrocortisone release from the gels containing of 1% to 3% of polysorbate 21 or 81, in the presence of 1,2-propylene glycol or PEG 200 conform to second order kinetics. Release rates in this stage are in the range from 3.80 x 10(-4)%.h-1 to 5.97 x 10(-4)%.h-1.

Studies on gynaecological hydrophilic lactic acid preparations. Part 4: Effects of polyvinyl pyrrolidone K-90 on properties of methylcellulose gels.

In continuing the investigation of the binding of lactic acid with basic polymers polyvinyl pyrrolidone K-90 (PVP) was used. Use of PVP in mixtures with lactic acid in experimentally determined and calculated proportions allowed the preparation of gels with pH 3.8-4.4, i.e. maintaining the physiological conditions in the vagina. The viscosity of the methylcellulose gels increases proportionally to the amount of the PVP--lactic acid complex added. Examination of the gels in the biopharmaceutical model, which simulated the physiological conditions of the vagina, allowed determination of the mobility of the preparations in patients.

Studies on dressings for oral cavity mucosa. Part 5: Properties of xerogel stomatological dressings with one-side antiadhesive coating.

The adhesion of xerogel dressings based on Eudragit (E), and methylcellulose (Mc) is in within the range of 143-270 g, and dissolution time of xerogel dressings in water is 3.4 h, and in artifical gastric juice 2.8 h. The 50% release time for Kunitz protease inhibitor ranges from 3.2-11.5 h.

Preliminary assessment of selected methacrylic acid--acrylic acid copolymers as factors buffering triethanolamine interacting with artificial skin sebum.

To allow cleaning of sebum ducts for acne prophylaxis the authors suggest use of triethanolamine buffered with anionic polymers of acrylic and methacrylic acid. In these preliminary researches addition of Eudragit L-100, Eudragit L-100-55 or Eudragit S-100 implicates decrease of pH of 1.49% triethahnolamine solution from 10.06 even to 7.20. Triethanolamine penetrates into the artificial skin sebum, gains hydrophylic properties, and reacted sebum increase in volume allowing mechanical remove of lipid bed. The highest triethanolamine penetration and the highest volume increase were observed after application of Eudragit S-100 complexes. Eudragit L-100 and L-100-55 proved milder action. These complexes may be applied for further examinations on acne prevention.

Influencia de los tensides en la liberaciónde las sustancias medicinales de los geleshidrófilos: influencia del polisorbato 20y polisorbato 80 en la liberación delhidrocortisona de los geles hidrófilos / Influence of tensides on liberation of medical agents from hydrophilic gels: effects of polysorbate 20 and polysorbate 80 on liberation of hydrocrotisone from hydrophilic gels

El proceso de liberación de hidrocortisona de los hidrogeles con la adición del 1 por ciento y del 3 por ciento del polisorbato 20 o polisorbato 80, en la presencia de propilenglicol - 1,2 o PEG 200, tiene dos fases. Durante la primera fase las velocidades de liberación son más altas, comparando con la segunda fase. La segunda fase de liberación corresponde a la cinética de primer orden. Los periodos de semiliberación en el transcurso de esta fase oscilan entre 15,67 y 23,50 (AU)

Studies on gynaecological hydrophilic lactic acid preparations. Part 3: Effects of chitosan on the properties of methylcellulose gels.

Methylcellulose gels comprising lactic acid, similarly to its water solutions, have pH values between 2.0 and 2.6, i.e. out of the physiological range. Addition of Chitosan enables preparation of gels with pH values from 2.2 to 4.9 similar to the natural vagina pH range, 3.8-4.4. The absolute viscosity of the gels, ranging from 27 up to 700 mPa.s, depends on chemical composition and on excess of lactic acid used. Measurement of adhesion enabled the selection of gels which remain located at the point of application under simulated biopharmaceutical conditions. The behavior of those preparations in the true environment of the vagina needs to be verified in vivo.

Studies on dressings for mucosa of the oral cavity. Part 4: Influence of technology used in the preparation of dental xerogel dressings in the presence of acetone on their properties.

Adhesion of xerogel dressings prepared on Eudragit-E 100, methylcellulose and glycerol compositions in acetone/water mixtures, remains within the range of 317-967 g, after addition of polyvinylpyrrolidone (PVP), it increases to 633-1200 g. Dissolution time of dressings in water amounts to 6 h, in artificial gastric juice to 3 h. Addition of PVP results in decrease of the elution rate, dissolution time amounts to 2.5 h. The Kunitz protease inhibitor semi-liberation times amount to 3.3-7.6 h.

Studies on dressings for mucosa of the oral cavity. Part 3: Effect of preparation technology on the physical and chemical properties of stomatological xerogel dressings.

Adhesion of xerogel dressings prepared on Eudragit (E), methylcellulose (MC) and glycerol compositions, remaining within the range of 625-650 g, after addition polyvinylpyrolidone (PVP) amounts to 450-1250 g. Dissolution time from xerogel dressings without PVP additive both in water and in an artificial gastric juice amounts to 3 h. Addition of PVP results in reduction of the elution rate. In dependence upon the PVP/E/MC ratio elution time amounts to 3-3.5 h. Pharmaceutical availability of the Kunitz protease inhibitor in particular groups of then dressings depends upon concentration of hydrophilizing agent. The semi-liberation times amounts to 3.65-17.50 h.

Studies on dressings for dental surgery use. Part 3: Effect of gamma-radiation and of formaldehyde on properties of gelatinous dental dressings.

Gelatinous dressings were exposed to gamma-radiation or treated with formaldehyde to improve their resistance to the proteolytic effects of trypsin. After aging of the preparations, both gamma-irradiated and blank samples of gelatinous dressings were etched at a constant rate. Etching rate of the formaldehyde treated dressings decreases during storage.

Studies on dressing for dental surgery use. Part 2. Influence of Kunitz' protease inhibitor on properties of dental gelatinous dressings.

To increase resistance of gelatinous dressings to the etching action of trypsin in vitro, the Kunitz' protease inhibitor has been added. It has been found that the etching rate of the dressings was reduced in proportion to the inhibitor added. Addition of plasticizers in the presence of an inhibitor reduces the etching rate of the dressings and the effect depends on the type and concentration of the plasticizer added. Thermally sterilized dressings have an average of 10% less resistance to the etching action of trypsin. The liberation of the inhibitor from the dressings follows first order kinetics, whereas its liberation rate depends upon the type of the plasticizer used.

Studies on dressings for dental surgery use. Part 1: Effect of plasticizers on gelatin gel etching rate.

For quantitative evaluation of the absorption rate of dental dressings made of gelatin, a biopharmaceutical model of etching of gelatin gels in vitro has been elaborated. For the optimum etching conditions of gelatin gel columns 900 BAEE units per ml trypsin solution was used at a temperature of 25 degrees C. It has been found, that addition of glycerol and propylene glycol insignificantly reduces the etching rate of gelatin gels, whereas the PEG 400, PEG 1500 and PVAL increase resistance of the gels against the etching action of trypsin. In the model provided well repeatable results the coefficient of variation of the average gel etching rate remained within the range of 0.45-0.57%.

Studies on antifungal properties of phenol complexes with secondary amines. 1. The effect of complex formation of nitro- and chlorophenols with dicyclohexylamine on the antifungal activity in vitro.

Inhibitory doses (ID50) of phenols complexed with dicyclohexylamine are lower (21.4-47.7%) than the inhibitory doses of free phenols. This is demonstrated in vitro by experiments with Aspergillus oryzae and Penicillium expansum on solid medium.

Studies on antifungal properties of phenol complexes with secondary amines. 2. Antifungal properties in vitro of the complex of 2,4,5-trichlorophenol with dicyclohexylamine.

In studies in vitro it has been found that 2,4,5-trichlorophenol in the form of a complex with dicyclohexylamine is two times more active an antifungal agent than free chlorophenol.

Studies on antifungal properties of phenol complexes with secondary amines. 3. The antimycotic activity of the complex of 2,4,5-trichlorophenol with dicyclohexylamine in the treatment of experimental mycosis.

2,4,5-trichlorophenol complexed with dicyclohexylamine was used for treatment of experimental mycosis. From the mycological and clinical evaluation the conclusion can be drawn that the effect of phenol in lipophilic ointment is comparable to that of clotrimazole (Canesten-cream "Polfa" licensed by Bayer) with the statistical significance p less than 0.001.

Studies on dressings for treatment of mucous membranes of oral cavity. Part 2: Influence of hydrophilizing substances on properties of hydrogel dressings comprising Kunitz protease inhibitor.

Resistance of the dressings against washing out depends upon concentrations of methylcellulose or sodium salt of carboxymethylcellulose, and upon concentrations of glycerol, 1,2-propylene glycol and polyoxyethylene glycol 400. For the determined group of dressings the ratio of washing out times in 0.9% sodium chloride solution to washing out times in distilled water remains constant. A similar relation has been observed for washing out times of the dressings in vivo compared to those in vitro in 0.9% solution of sodium chloride. The pharmaceutical availability of the Kunitz type protease inhibitor depends upon composition of the gel forming and hydrophylizing substances in the dressings. The rheological characteristics of the dressings comprise a flow limit and thixotropic properties. The initial clinical examinations proved that the dressings alleviated symptoms of paradontopathy.