Romána Zelkó

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.

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.

The effect of water on the solid state characteristics of pharmaceutical excipients: Molecular mechanisms, measurement techniques, and quality aspects of final dosage form

In this paper we give an overview about the interaction of water molecules with pharmaceutical excipients. Most of these excipients are amorphous or partially amorphous polymers and their characteristics are very sensitive to the water content. In the course of the manufacturing processes water sorption is possible, therefore in some cases it is important to strictly control the residual moisture content of a dosage form. There are several mechanisms of water sorption, like water is able to bind to polar groups of hygroscopic excipients and could also exist in the capillary system of amorphous excipients. Several techniques are available to characterise the states of water inside the materials and the effects of residual water on polymers. For this purpose water sorption measurements, differential scanning calorimetry and the Fourier-transform infrared spectroscopy are reviewed. The importance of water content and storage conditions of pharmaceuticals on the properties of the final dosage forms are also demonstrated with practical examples.

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.

Effect of the Storage Conditions on the Tensile Strength of Tablets in Relation to the Enthalpy Relaxation of the Binder

Stubberud (8) reported on the weakening effect of moisture Effect of the Storage Conditions on the sorption on the tensile strength and the physical stability of Tensile Strength of Tablets in compacts of crystalline and partly amorphous lactose, alone and in binary mixtures with PVP. Alderborn and Ahlneck (9) Relation to the Enthalpy Relaxation of assessed the effect of air humidity on the post compaction the Binder changes in tensile strength of tablets formulated with different pharmaceutical excipients. They found that changes in tablet strength were probably due to a rearrangement of solid material within the tablet that was facilitated by sorbed water. Rees F. Kiekens,1 R. Zelko,2 and J. P. Remon1,3 and Tsardaka (10) examined the effects of moisture on the viscoelastic deformation during compaction of modified starch Received September 8, 1999; accepted January 7, 2000 using creep tests and Heckel plots. They reported that the moisture, by facilitating elastic and plastic deformation, not only

Polymer structure and antimicrobial activity of polyvinylpyrrolidone-based iodine nanofibers prepared with high-speed rotary spinning technique.

Poly(vinylpyrrolidone)/poly(vinylpyrrolidone-vinylacetate)/iodine nanofibers of different polymer ratios were successfully prepared by a high-speed rotary spinning technique. The obtained fiber mats were subjected to detailed morphological analysis using an optical and scanning electron microscope (SEM), while the supramolecular structure of the samples was analyzed by positron annihilation lifetime spectroscopy (PALS). The maximum dissolved iodine of the fiber samples was determined, and microbiological assay was carried out to test their effect on the bacterial growth. SEM images showed that the polymer fibers were linear, homogenous, and contained no beads. The PALS results, both the o-positronium (o-Ps) lifetime values and distributions, revealed the changes of the free volume holes of fibers as a function of their composition and the presence of iodine. The micro- and macrostructural characterisation of polymer fiber mats enabled the selection of the required composition from the point of their applicability as a wound dressing.

Prediction of oral disintegration time of fast disintegrating tablets using texture analyzer and computational optimization

One of the promising approaches to predict in vivo disintegration time of orally disintegrating tablets (ODT) is the use of texture analyzer instrument. Once the method is able to provide good in vitro in vivo correlation (IVIVC) in the case of different tablets, it might be able to predict the oral disintegration time of similar products. However, there are many tablet parameters that influence the in vivo and the in vitro disintegration time of ODT products. Therefore, the measured in vitro and in vivo disintegration times can occasionally differ, even if they coincide in most cases of the investigated products and the in vivo disintegration times may also change if the aimed patient group is suffering from a special illness. If the method is no longer able to provide good IVIVC, then the modification of a single instrumental parameter may not be successful and the in vitro method must be re-set in a complex manner in order to provide satisfactory results. In the present experiment, an optimization process was developed based on texture analysis measurements using five different tablets in order to predict their in vivo disintegration times, and the optimized texture analysis method was evaluated using independent tablets.

Influence of drying temperature and granulation liquid viscosity on the inter- and intragranular drug migration in tray-dried granules and compacts.

The influence of the drying temperature and granulation liquid viscosity on the inter- and intragranular migration of a poorly water-soluble compound in a granulation mass and in a compact was quantitatively assessed. The intergranular migration kinetics were investigated by evaluating the drug distribution at different drying-time intervals. The results were analyzed by use of two-factor, three-level, face-centered, central composite designs. Riboflavin was mixed with α-lactose monohydrate 90 M and granulated with distilled water, except for the viscosity experiments in which an aqueous polyvinylpyrrolidone (PVP) (Kollidon K90) solution was used. The wet granules were dried in a hot-air oven or compacted prior to drying. The drug concentration at different locations inside the granulated mass and the compacts after drying was determined spectrophotometrically and by use of diffuse light reflectance measurements. The riboflavin distribution in the granulation masses and in the compacts was characterized by drug-enriched outer layers and drug-depleted inner regions, indicating a strong migration phenomenon. It was clear that the drying temperature had no influence on the inter- and intragranular drug distribution. The intergranular migration was avoided using the PVP as a binder in the granulation liquid, whereas a minimal granulation liquid viscosity of 100 mPa · sec was necessary to avoid the intragranular migration. The diffuse light reflectance measurements can be used for the in-process control of granule samples containing low drug concentrations without the destruction of the samples.