I. Rácz

The effect of liquid crystalline structure on chlorhexidine diacetate release.

The aim of this study was to examine different liquid crystalline preparations containing chlorhexidine diacetate and to find connection between their structure and the kinetic of drug release. Nonionic surfactant, Synperonic A7 (PEG(7)-C(13-15)) was selected for the preparation of the examined liquid crystalline systems. Mixtures of different ratios of Synperonic A7 and water were produced. By increasing the water content of the systems, lamellar and hexagonal liquid crystal structures were observed. For the analysis of the prepared liquid crystalline systems polarising microscopy, rheology study, differential scanning calorimetry and dynamic swelling tests were carried out. The chlorhexidine diacetate release was examined by Franz-type vertical diffusion cell apparatus. The chlorhexidine diacetate release from hexagonal liquid crystalline preparations was characterised by zero-order release kinetics, while the drug release from lamellar liquid crystalline systems was described by anomalous (non-Fickian) transport. The results indicate that the drug release kinetic is strongly dependent on the liquid crystalline structure.

Evaluation of mathematical models describing drug release from lipophilic matrices

Potassium chloride, as a highly watersoluble model drug was embedded into wax to produce sustained release dosage form. Samples were coated with different core:wall ratios to control the dissolution profile. The drug release from coated samples was tested by the rotating paddle method of USP and the dissolution data were analyzed assuming different kinetic models. Increasing the quantity of coating material may modify the drug liberation which was demonstrated by the correlation between proportion of the embedding material and mean dissolution time. It can be concluded that changing the quantity of embedding material both the dissolution rate and kinetic profile can be controlled.

Dissolution and diffuse reflectance characteristics of coated theophylline particles

The aim of the present study was to investigate how the dissolution and diffuse reflectance characteristics of theophylline microcapsules were influenced by the changes in the thickness and by the plasticizer content of coating. Microencapsulation was carried out in laboratory fluidized-bed system using water dispersable Eudragit-type film coating polymer. United States Pharmacopeia rotating paddle method was applied for the in vitro dissolution study. The dissolution profile of the produced microcapsules was evaluated by Weibull distribution. The effect of the thickness of coating and that of the plasticizer content on the dissolution kinetics was modelled by a second-order polynomial equation fitted to the data gathered by a face-centered central composite statistical design. It was found that both of the examined coating parameters influenced the drug release kinetics. The diffuse reflectance spectra of the coated particles indicated the changes in coating parameters without destructive analysis of samples.

Effect of plasticizer on the dynamic surface tension and the free volume of Eudragit systems.

The purpose of the present study was to determine the changes of dynamic surface tension of aqueous Eudragit dispersions quantitatively and compare these data with the free volume of the free films formed from several dispersions of different dibutyl sebacate (DBS) concentrations. Eudragit L 30D and Eudragit RL 30D aqueous colloidal polymer dispersions and their cast free films were examined. The concentration of DBS varied in the dispersions from 0 to 20%. The dynamic surface tension of the dispersions were measured by the Du Nouy ring method while the free volume of cast films were determined by positron annihilation spectroscopy. The obtained results show that dynamic surface tension measurements indicate the white point (WP) of Eudragit dispersions by a significant standard deviation increase. This may suggest the applicability of dynamic surface tension measurements for the determination of the WP of polymeric dispersions. A decrease in the WP temperature of Eudragit dispersions with an increasing plasticizer concentration was observed up to the DBS concentration of 10% w/w. Above this concentration neither the WP of the polymer dispersion nor the free volume of the free films of the polymer were changed remarkably.

Effect of the formulation parameters on the characteristics of pellets

Pelletization is increasingly applied currently for the preparation of solid oral controlled-release dosage forms. The production of the particles, which are regular in shape and size, can be achieved with the application of the proper polymer auxiliary materials and new pharmaceutical technological methods (extrusion, spheronization). Regularity in shape and size, attained by the optimization of several production parameters, can promote the coating procedure. Under optimal conditions, particles were prepared for coating in a high-shear mixer, which is used to produce uniform particles. The effect of the rotating speed of the applied chopper and the amount of microcrystalline cellulose in the composition on the physical characteristics of the pellets was modeled by a second-order polynomial equation fitted to the data gathered by a face-centered central composite statistical design.

Influence of chlorhexidine species on the liquid crystalline structure of vehicle

The aim of this study was to investigate the influence of three chlorhexidine species, chlorhexidine base and its salts (diacetate and digluconate), on the physico-chemical features of liquid crystalline systems and on drug transport through lipophilic membranes. Nonionic surfactant, Synperonic A7 (PEG(7)-C(13--15)) was selected for the preparation of the liquid crystalline systems. Mixtures of different ratios of Synperonic A7 and water were prepared. The liquid crystalline systems were characterized using polarizing microscopy, small-angle neutron scattering and transmission electron microscopy. Membrane transport was also examined. The addition of chlorhexidine species to the liquid crystalline system modified the structure of the liquid crystalline system. As a result of liquid crystal--drug interaction, the solubility of chlorhexidine base and its diffusion through lipophilic membranes increased in comparison with those of the chlorhexidine salts.

Effects of Storage Conditions on the Free Volume of Polyvinylpyrrolidone: Comparison of Positron Lifetime Data with the Tensile Strength of Tablets

9 batches of 300 tablets were produced using a wet granulation procedure beginning with the mixing of 100 g Anhydrous Received February 17, 2000; accepted May 4, 2000 theophylline (Ph.Hg. VII., Hungaropharma, Budapest, Batch No. B-16263.95) and 10 ml of a 15% (w/v) Kollidon 25 aqueous

Effect of chemical properties on drug release from hydrophobic matrices

The drug release of modified release matrix systems is often governed by erosion as well as by diffusion through the matrix. The purpose of the present work was to study the release kinetic parameters of inorganic and organic water soluble drugs from hydrophobic wax matrix systems, produced by melt coating. The drug release process was investigated both experimentally and by means of mathematical models. Different models (first order, cube root, square root, two-third root) and the Weibull distribution were applied for the evaluation of the drug release data. On the basis of our results, it can be concluded that not only the ratio but the chemical characteristic of the drug and the matrix base material as well determine the rate of drug release.

Coating Polymer-plasticizer Interaction in Relation to the Enthalpy Relaxation of Polymer

In the course of the formulation of coated dosage forms, the selection of the suitable composition of the coating system is of great importance in respect of the final dosage form. Since the applied coating systems are multicomponent, the possible interactions between the components determine the physico-chemical stability of the formulated dosage form, the drug release process, as well as the formulation parameters. In the present study, the influence of the applied plasticizer, dibutyl sebacate on the enthalpy relaxation of casted Eudragit L 30D films was determined as a function of the plasticizer concentration. The enthalpy relaxation was recorded by DSC during the applied isothermal recovery process of Eudragit films. The obtained results indicate that enthalpy relaxation can be measured by DSC at 20 mass/mass% dibutyl sebacate concentration, which refers to the increased molecular mobility consequently to the effect of the interaction between the polymer and plasticizer.

Effect of Polysorbates on Drug Release from Wax Matrices

The purpose of this study was to investigate the effect of various types and amounts of polysorbates on potassium chloride release. Potassium chloride, which is a highly water-soluble model drug, was embedded into wax (containing surfactants) to produce a sustained-release dosage form. Various kinds of polysorbates were chosen as surfactants to control the dissolution profile. The release of the model drug was tested by rotating paddle method of USP 23 and the dissolution process was characterized by the Weibull distribution. The surface tension of the aqueous solutions of polysorbates was determined by a computer-controlled Sigma 70 tensiometer. The application of polysorbates in more than 2% concentration did not alter either the release rate of the embedded potassium chloride, or the surface tension values of the aqueous solutions. The results of this study allow the determination of the optimal concentration of polysorbates in the case of the potassium chloride release.