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.

Modeling of subdivision of scored tablets with the application of artificial neural networks.

The subdivision of scored tablets is an important problem for the exact individual therapy of patients. The recent guidelines of the EU require verification of the equal mass of the tablet halves, but this problem has previously never been investigated in papers published on the production technological aspects. Our aim was therefore to study the effects of the physicochemical properties of the raw materials and the effects of the compression process on the breaking parameters of the tablets. Artificial neural networks (ANNs) were applied for data analysis and modeling, which are very useful optimizing systems. The abilities of four different types of ANNs to predict the parameters of the compression process and the tablets were compared. The radial basis function and multilayer perceptron ANNs furnished statistically significant better results than linear or generalized regression neural networks. These ANN models revealed that the subdivision of scored tablets is strongly influenced by the production parameters and the compositions of the powder mixtures.

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.

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.

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.

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.

Influence of Avicel PH-301 on the compressibility of alpha-methyldopa and phenobarbitone in direct compression.

The aim of this work was to investigate the compressibility behavior of alpha-methyldopa and phenobarbitone using a Korsch EK0 instrumented eccentric tablet machine, with force-time and force-displacement curves constructed and applied to calculate different compressional values to study the compressional behavior. The results of this work revealed a difference in compressibility behavior between the two drugs during the compressional process. alpha-Methyldopa gave an abnormal compressional curve with high friction in the pre- and postcompressional phases. A residual force could be seen on the lower punch. Furthermore, capping and sticking were observed visually during tablet pressing, indicating poor compressibility behavior. In the case of phenobarbitone, no friction was observed in the precompressional phase, but there was higher friction in the postcompressional phase, especially in the ejection phase. The compressibility of the drugs was improved by the addition of Avicel PH-301 and magnesium stearate.

[Preparation of pellets with a centrifugal granulator]. / Pelletek elöállítása centrifugál-granulátorban.

It has been investigated how the centrifugal-granulator is applicable to form paracetamol pellets with good mechanical, powder rheological and dissolutional properties. During the preparation process the mechanical parameters were the same only the percentage of the effective material was changed. The authors found that the centrifugal-granulator is well applicable to form good pellet particles which have good dissolution and mechanical parameters to from needle shaped raw materials.

[Water uptake of tablets, their disintegration and dissolution are in close relation]. / A vízfelvétel, a dezintegráció és a hatóanyag-kioldódás kapcsolatának vizsgálata tablettákban.

Authors investigated the factors influencing this connection on phenylbutazone tablets. Tablets were prepared by wet granulation using three binders (gelatine, hydroxypropyl-cellulose, hydroxyethylcellulose) in different concentrations. Three disintegrants were compared (polyvinylpolypyrrolidon, formalin-casein and cyclodextrin polymer) on the basis of their disintegrating and dissolution-enhancing properties. It was found, that the binder having surface activity improves the wetting of phenylbutazone tablets. Increasing the concentration of gelatine solution, tablets became harder, disintegrated very slowly and the active agent hardly dissolved. Among disintegrants the polyvinyl polypyrrolidon was found to be the best. This material increases the hardness and the drug release as well. The use of cyclodextrin polymer is limited because of the slow water uptake of its tablets. The water uptake of nondisintegrating tablets was described with the Washburn equation. Water penetrates into disintegrating tablets according to the Weibull distribution. The penetration rate can be characterized with the "characteristic water penetration time (t63.2%), obtained from the Weibull equation. The difference between nondisintegrating and disintegrating tablets can be observed in the dissolution kinetic, too. The drug dissolves from the nondisintegrating tablets according to Noyes-Whitney equation (Eq. 1.), from disintegrating tablets according to the modified Noyes-Whitney equation (Eq. 2.) or Weibull equation (Eq. 3.). The dissolution rate constant (K) obtained from the modified Noyes-Whitney equation is proportional with water uptake and in inverse.

[Deformation of tablets according to breaking hardness]. / Tabletták deformációjának tanulmányozása nyomási szilárdságvizsgálat alapján.

The authors were the first to test the breaking process of tablets in home respect. In experiments on the breaking of tablets a tablet hardness tester developed by the Chemical and Pharmaceutical Works Ltd. Chinoin (Budapest) was used. With an appropriate program, this permitted not only a qualitative evaluation of the breaking curves (Fig. 2-4.) also an assessment of the breaking work relating to the breaking strength and even the work needed for various deformation processes (Tab. I-II.). The concept of the breaking factor was introduced: this allows a differentiation of tablets even if the breaking strengths are the same (see Tab. III. 1-2 tablets; with two samples analysis; p < 0.05.) It is concluded that such breaking strength examinations contribute to a better understanding of the behaviour of substances during compression. These results can be very useful both in preformulation examinations and in tests on the prepared products.

[Use of galactomannan to produce hydrophilic matrix tablets]. / Galaktomannán felhasználása hidrofil mátrix tabletták elöállításában.

Galactomannan currently seems to be a very promising auxiliary. The aim of the present work was to examine the applicability of this auxiliary in tablet-making. Galactomannan is a polysaccharide composed of galactose and mannose, which is distributed by the Swiss firm Meyhall under the name Meyprogat. The products are numbered according to their molecular weight and polymeric degree. Thus, Meyprogat 7, 30, 60, 90, 120 and 150 can be discriminated. It is used in many areas, for example in the food industry as a stabilizing agent, and in medical therapy to cure diabetes and hyperlipidaemia. In pharmaceutical technology, it is used in low concentration (5-10%) as a disintegrant agent and in high concentration (25%) as binding agent. It is able to form a hydrophilic matrix, which results in sustained release. Theophylline was chosen as model agent. After the preformulation examinations, granulations were made by a wet method, and after this tablets were formed. Examinations were made of the granulations, the physical parameters of the tablets were determined, and the release of the effective agent from the tablets was studied. The following conclusions were drawn: 1. Galactomannan yields tablets with very good hardness. 2. Galactomannan is suitable for the formation of hydrophilic matrix tablets. Through use of this macromolecular agent, the rate of dissolution can be influenced in accordance with the desired purpose.

[Deformation phenomena occurring during compression. III. Changes of maximal compression strength in quasi-static condition]. / Adatok a préselés során bekövetkezö deformációs jelenségek tanulmányozásához. III. A Kvázi-sztatikus állapotban mért maximális préselési eröváltozás vizsgálata.

Four materials of different properties in respect of compressibility, lactose, sodium chloride, microcrystalline cellulose (Avicel PH 101) and so-called simple granulate were investigated. In function of time and that of actual pressing force decrease of axial force on upper punch were measured in quasi-state. Evaluating relations it was established that both pressing time and pressing force had influence on deformation structural changes occurring inside compressed form. Furthermore, summing up of results showed that useful conclusions could be drawn from diagrams--which represented decrease of force--to compressibility properties of materials too.