Study of the compressibility of chewing gum and its applicability as an oral drug delivery system.

Medicated chewing gum tablets were prepared and evaluated as an oral drug delivery system. The morphology and surface free energy of the components were characterized, and the tablets were prepared by direct compression with an instrumented eccentric tableting machine. The compressibility, the porosity and the texture of the tablets were investigated and the dissolution of the active pharmaceutical ingredient (caffeine) from them was tested with a specially-developed method. Cafosa gum base is a co-processed product which is compressible. Because of the sticking of the tablets to the punches and the high friction that arises during ejection from the die, the use of lubricants and suitable (e.g. Teflon-coated) punches is necessary on a production scale. For this purpose, magnesium stearate with high specific surface area was applied. The release of caffeine in response to the mechanical effect applied proved to be rapid and quantitative and the profile closely obeyed the Korsmeyer-Peppas equation, which is valid in the case of matrix systems. Medicated chewing gum tablets can be used as matrix tablets for oral pharmaceutical administration.

[Formulation and special investigations of innovative intraoral solid dosage forms.] / Not available.

During our work, we summarized the types of solid dosage forms which were in the focus of attention in the last years because of their innovative pharmaceutical technology solution and simple use. The biopharmaceutics of solid dosage forms for intraoral use and the advantages of the use of these dosages forms were presented in general. However, these dosage forms cannot always be prepared with conventional pharmaceutical processes, therefore the special pharmaceutical solutions which can be applied for their preparation were presented. In addition to testing the European Pharmacopoeia dosage forms, the special tests which can be applied for the characterization of innovative solid dosage forms were highlighted.

Formulation study of directly compressible chewable polymers containing ascorbic acid.

The topic of this article is the compression physics of different gum bases which can be used to prepare chewing gum tablets by direct compression. Three different gum bases, Pharmagum(®) C, M and S, were tested alone and in different combinations. The preparations were compressed with a Korsch EK0 eccentric tableting machine at compression forces of 5, 7.5, 10, 12.5 and 15 kN. The compression and breaking processes and the physical parameters of the tablets were investigated. The results revealed that increase of the compression force did not significantly change the studied parameters of the tablets.

Effects of lecithin on the mechanical properties of hydroxypropylmethylcellulose free films.

The effects of the biocompatible surfactant lecithin (a pigment-stabilizing agent) on the mechanical properties of free hydroxypropylmethylcellulose films were evaluated. The film thickness and the characteristics of the deformation curve were not altered relevantly by the incorporation of lecithin. The deformation force decreased markedly when the lecithin content of the film exceeded 5%.

Comparison of the halving of tablets prepared with eccentric and rotary tablet presses.

The aim of this study was to compare the densification of powder mixtures on eccentric and rotary tablet presses and to establish relationships with the halving properties of the resulting scored tablets. This is an important problem because the recent guidelines of EU require verification of the equal masses of tablet halves. The models of Walker, Heckel, and Kawakita were used to describe the powder densification on the two machines. The calculated parameters revealed that the shorter compression cycle of rotary machines results in poorer densification and lower tablet hardness at a given compression force. This is manifested in poorer halving properties, which are influenced mainly by the hardness. Better densification improves the halving even at lower tablet hardness. This demonstrates that these parameters can be good predictors of tablet halving properties.

Pretreatment of pigments to prepare liquids for enteric coating.

Film coating fluids commonly contain different pigments. The objective of this work was a study of the distribution of these particles in the coating film. Different pretreatment forms (pigment suspension, pigment paste and untreated pigments) were applied. They were incorporated into a Eudragit L 30 D-55 dispersion. The surface roughness and the mechanical properties of the free films indicated, that the most homogeneous film was obtained with the pigment paste. The homogeneity of the film was investigated by mechanical testing. The protective effect of the coating did not vary with the application of pigments in different forms, but the appearance of the coated tablets underwent a considerable change.

Metolose-PEG interaction as seen by positron annihilation spectroscopy.

The plasticizing effects of poly(ethylene glycol) (PEG 400) on methylcellulose (Metolose) cast films were studied by conventional physicochemical methods and positron annihilation spectroscopy. The PEG concentrations relative to the total polymer content were varied within the range 0-75% (w/w). At low concentrations (below 33.3%, w/w), the plasticizer was found to build in into the methylcellulose structure. On the other hand, at higher concentrations (above 50%, w/w), it formed small separate phases in the films. Positron annihilation spectroscopy (PALS) was applied to track the Metolose-PEG interaction. Controlled ageing of Metolose-PEG films at room temperature and at 75% RH revealed a significant difference between the ageing processes of the monophase and those of the separate phase films. The ageing involves two steps in both cases: a fast and a slow one. The PALS measurements demonstrated that the slow process is hindered in the phase-separated samples.

Study of deformation process of stored polymethacrylate free films.

In the present study the effects of the additives and of storage on the deformation of films prepared from methacrylic acid/ethyl acrylate copolymer with and without polysorbate 80 were evaluated. The films containing polysorbate 80 revealed a longer deformation process with a different deformation curve shape and higher force and work of deformation. Storage induced very significant changes in the characteristics of the films. The decrease in the deformation work was more relevant than the reduction in the deformation force. Increase of the storage time increased the changes in these parameters. The presence of polysorbate 80 in the films reduced the change in behaviour of the films at lower relative humidity.

Examination of homogeneity with X-ray beams.

The effects of blending time and rotation speed on the homogeneity of powder blends were examined. The concentrations of the samples were measured with an energy-dispersive X-ray fluorescence analyser, and control measurements were made with a UV spectrophotometer. The paired sample t-test showed that, for a large majority of the samples for which measurements were made to determine the concentrations, there was no essential difference. It may be stated, in accordance with the fitted equation, that the rotation speed and the square of the blending time exert significant effects on the distribution of the active ingredient. The energy-dispersive X-ray fluorescence analyser can be applied well for direct determination of the homogeneity of certain powder blends.

Iron(II) sulfate release from drop-formed lipophilic matrices developed by special hot-melt technology.

Iron(II) sulfate-containing lipophilic matrices were developed by a special hot-melt technology (melt solidification in drops), using stearin, white wax and their mixture as conventional bed materials. The special technology resulted in spherical particles which can be filled directly into capsules; these store iron as a depot and ensure a slow and uniform release, whereby the irritation of the gastric mucosa by the iron can be decreased. The rates of dissolution of the iron(II) sulfate from the various lipophilic matrices were different, but fundamentally low. Kinetic calculations demonstrated that the rate of dissolution of the iron(II) sulfate was of approximately zero kinetic order. The results of in vivo experiments on rabbits correlated well with the in vitro data. The plasma curves for the animals treated with the iron(II) sulfate preparations varied with the excipients in the depot products. The properties and ratio of the bed materials influenced the release of the iron(II) sulfate. In all probability, the release of the active agent can be regulated through the use of a melt of stearin and white wax in different ratios. The development products functioned as a sustained-release system and ensured elimination of the irritation of the gastric mucosa. At the same time, the results justified the applicability of the special hot-melt technology in the development of the solid dosage form.

Study of in vitro and in vivo dissolution of theophylline from film-coated pellets.

Tests were performed on the influence of polymer coating films on the rates and the extents of in vitro and in vivo liberation of theophylline from pellets. Uncoated and coated pellets were used in the experiments. The coating material was Eudragit L; The film thickness was varied. The in vivo liberation of theophylline was studied in rabbits. The serum level of the released drug measured with a TDX Analyser. No appreciable difference was observed between the uncoated and the coated pellets as concern the maximum release data, but a significant shift was found in t(max) for Eudragit L coated pellets.

Drugs affecting brain dopamine interfere with the effect of Z-prolyl-D-leucine on morphine withdrawal.

The dipeptide Z-prolyl-D-leucine (Z-Pro-D-Leu) has been demonstrated to inhibit the development of tolerance to and dependence on morphine in the mouse. Since the dipeptide affects dopamine (DA) utilization in the terminal regions of the mesolimbic and nigrostriatal DA-ergic projections, the question has been studied of whether DA-ergic mechanisms are involved in the action of Z-Pro-D-Leu on morphine withdrawal. Both inhibition of tyrosine hydroxylase by alpha-methyl-p-tyrosine (alpha-MPT) and inhibition of DA receptors by pimozide interfere with the effect of Z-Pro-D-Leu on naloxone-precipitated morphine withdrawal. Inhibition of serotonin (5-HT) synthesis by DL-p-chlorophenylalanine (PCPA), on the other hand, does not modify the effect of the dipeptide. The results argue for a role of DA-ergic mechanisms in the effect of Z-Pro-D-Leu on the development of morphine dependence.

[On the polymorphism of barbiturates in powders and tablets - Part 3: The effect of the pressing power on the modification of barbital (author's transl)]. / Zur Polymorhqie der Barbiturate in Pulvern und Tabletten. 3. Mitteilung: Einfluss des Pressdruckes auf Barbital-Modifikationen.

The authors took X-ray diffraction pictures from two commercial brands of barbital (produced in the GDR and in the Hungarian People's Republic, respectively), the interpretation of which convinced them that these two commercial brands are different modifications. These crystals were brought by pressure (10 and 20 kN) into the shape of tablets. Textural studies showed that both commercial brands are easy to compress. An increase in pressing power caused insignificant changes in the structure of the GDR product; and in the Hungarian commercial product, only slight changes were observed. It could be proved by X-ray diffraction analysis that the form of the barbital crystals is affected by the application of pressure. But this change occurs already under a pressure less than 10 kN. A further increase in pressing power produces no further changes in crystal structure.

[On the Polymorphism of barbiturates in powders and tablets. Part 4: the dissolution of barbital B and barbital A (modifications I and III and their release from tablets (author's transl)]. / Zur Polymorphie der Barbiturate in Pulvern und Tabletten. 4. Mitteilung: Auflösung von Barbital B und A (Modifikation I und III) und deren Freisetzung aus Tabletten.

Two commercial brands of barbital (A: German Democratic Republic, modification III; B: Hungarian Peopl's Republic, modification I) were used to study the solubility and dissolution of the modifications. Crystals of these two substances were brought into the shape of tablets, the physical parameters and textural properties of which were determined. The effect of polymorphism on the release of these substances is discussed in the light of the results obtained from this investigation. The discussion will be continued and summarized in a subsequent paper, including further modifications.

[On the polymorphism of Barbiturates in powers and tablets. Part 5: The dissolution of recrystallized barbital substances and their release from tablet (author's transl)]. / Zur Polymorphie der Barbiturate in Pulvern und Tabletten. 5 Mitteilung: Auflösung umkristallisierter Barbital-Substanzen und Freisetzung aus Tabletten.

The dissolving characteristics of 6 different barbital modifications have been studied. With one exception, the metastable forms dissolved more rapidly than the stable form. The observed differences were not always significant. Substances recrystallized from an acetone-water mixture were less soluble in aqueous solvents than those recrystallized from water. The dissolving characteristics are changed by tabletting, the stable modification being more favourable in this respect. The solubility of barbital A2 was very poor. Consequently, it is not suited for therapeutic use. The dissolution rate was determined by means of the rotating basket method as described in the nineteenth edition of the U.S.P.

[On the polymorphism of barbiturates in powders and tablets. 6: Properties and behaviour of a spray-dried barbital preparation]. / Zur Polymorphie der Barbiturate in Pulvern und Tabletten. 6. Mitteilung: Eigenschaften und Verhalten eines sprühgetrockneten Produktes von Barbital.

The manufacture of a spray-dried barbital preparation is described, the properties, tabletting behaviour and release of which were studied in comparison to the initial substance. Spray-drying led to a compression-resistant mixture of amorphous and crystalline particles. As most of these particles have a spherical shape, the tablets obtained from this mixture were of great compactness, which inhibited the penetration of the medium and, consequently, delayed the release of the drug, too.

[On the polymorphism of barbiturates in powders and tablets. Part 1: Crystal optical studies on, and melting behaviour of barbital (author's transl)]. / Zur Polymorphie der Barbiturate in Pulvern und Tabletten. 1. Mitteilung: Kristalloptische Untersuchungen und Schmelzverhalten von Barbital.

Crystal optical studies showed that barbital brands that conform to the standards of the DAB 7--DDR and the Ph. Hung. VI, respectively, present two different crystalline forms. After recrystallization form water or acetone-water mixture (1:1), the optical crystal picture of the brand conforming to the DAB 7--DDR prevails. The melting points of the commercial products do not differ from each other; both substances melt at 187.5 degrees C, whereas the melting points of the recrystallized products are 1.5 degrees and 2 degrees C, respectively, lower.

[The texture and properties of sulfaethidol tablets]. / Untersuchungen über die Textur und die Eigenschaften von Sulfaethidol-Tabletten.

Scanning-electron-microscopic and X-ray diffractometric studies on the effect of the pressing power on the physical parameters of compressed tablets and on the texture of tablets containing sulfaethidol as the active principle, have shown that the crystal structure remains unchanged. The alterations observed in the physical parameters can be explained on the basis of present knowledge of the texture.

Release kinetics of potassium aspartate in polyvinyl chloride matrix formulation.

The authors prepared potassium aspartate matrix tablets in combination with polyvinyl chloride. The physical parameters were measured and the dissolution rates were determined. During the in vitro release rate experiments, it was determined that the dissolution kinetics obey both zero order and Higuchi diffusion model order kinetics.

[The liberation of phenylbutazone from tablets]. / Untersuchung der Freisetzung von Phenylbutazon aus Tabletten.

The liberation of phenylbutazone from tablets prepared by wet granulation was examined. It was found that the solution process can be described by the equation c = cs (l-e-K.t alpha). The influence of the binder concentration and the disintegrant on the liberation rate was also studied. The increase of the Klucel MF concentration accelerated the liberation of the agents. Among the disintegrants Polyplasdone XL and cyclodextrin block polymer turned out to be very good.