Indirect Methods For Determination of The Protective Effects of Coating Films on The Surface of Crystals

The extents of the protective effects of coating films on the surface of crystals were determined. Three different samples were made with different quantities of coating fluid (Sepifilm LP 010 in 10% aqueous solution). Since the atomizing rate was constant, the coating time increased in parallel with the volume of coating fluid applied. The direct measurement of film thickness and smoothness is very difficult, and therefore indirect methods were used. Dimenhydrinate was chosen as model drug; this is a heat-sensitive antihistamine with a low melting point. This temperature can be reached during the tableting process. The behaviour of samples on exposure to heat was examined by differential scanning calorimetry. The water uptakes of the samples were determined with an Enslin apparatus. Plasticity was studied with an instrumented tablet machine. These indirect methods (thermal conductivity, water uptake and plasticity measurements) revealed connections between the results of the various experiments. An overlong coating time decreased the protective effect of the coating film. This revised version was published online in August 2006 with corrections to the Cover Date.     

Surface Treatment of Dimenhydrinate Crystals

Dimenhydrinate is a heat-sensitive antihistamine with a low melting point. The heat-sensitive feature is of importance if direct compression is used. Direct measurement of the heat originating in the texture of tablets during compression is very difficult. Thermoanalytical methods were used as indirect methods to describe the changes in material properties at high temperature: differential scanning calorimetry, thermomicroscopy and thermogravimetric analysis. Film coating method is widely used in pharmaceutical technology. A fluidized bed apparatus was applied to coat the crystals. The coating film forming agent was hydroxy-propyl-methylcellulose (HPMC), which is a gastric-soluble polymer. Thermoanalytical measurements reveal that dimenhydrinate crystals are sensitive to heat. Film coating method does not alter the shape of the DSC curve of dimenhydrinate, but increases the melting point. The presence of a macromolecular film reduces the thermal conductivity, because it separates the particles. This revised version was published online in August 2006 with corrections to the Cover Date.     

Pelletization of needle-shaped phenylbutazone crystals

The flowability of needle- or plate-shaped crystals is very poor and the direct compression of these crystals is difficult. Commercial phenylbutazone consists of needle crystals and it has three polymorphs.The aim of this work was to investigate the solid-state thermal stability of phenylbutazone at condition of the pelletization process (40°C; 60 min). The other aim was the preparation of phenylbutazone pellets with centrifugal granulator.Based non the flowability and the other parameters of, the pellets, they are suitable for capsule filling or tabletting. The centrifugal granulation and the conditions were favourable for the preparation of pellets from phenylbutazone in the form of needle crystals.This revised version was published online in November 2005 with corrections to the Cover Date.     

Evaluation of phenomena occurring during the preparation of matrix granules by the hot melt technique

The aim of this study was to evaluate the applicability of hot melt granulation for the formulation of a pH-sensitive intelligent tablet containing heat- and moisture-sensitive components. An appropriate combination of magnesium trisilicate, aluminium hydroxide, sodium bicarbonate, and basic butylated methacrylate copolymer (Eudragit E PO) exhibited a good disintegration profile, but poor processibility. Hot melt granulation was applied with the aid of polyethylene glycol 2000 to increase the tablettability. The effects of the composition and the process on the properties of the granules and tablets formed were assessed with thermoanalytical and conventional testing methods. The heating of mixtures containing basic butylated methacrylate copolymer (Eudragit E PO) below its glass transition caused a relevant change in the wettability of the granules. This was induced by an alteration in the microstructure of the agglomerates. Tablets prepared from the granules containing an appropriate ratio of polymers exhibited an appropriate mechanical and disintegration profile. The thermal behaviour of the mixture of polymers cannot be predicted from the properties of the starting materials. Their interaction, demonstrated by DSC, can cause significant structure-forming problems in the matrices. The parameters of the granules and tablets varied with the quantity of the polymer applied. With an appropriate combination of polymers, hot melt granulation can be a suitable method for the preparation of intermediates for the formulation of controlled-release antacid tablets. Thermal analysis can promote an understanding of the process and determination of its operational parameters.     

The effect of storage on the behaviour of Eudragit NE free film

Eudragit NE 30 D aqueous dispersion is a commonly used coating material, which contains methacrylate copolymers as film-forming agent and nonoxynol 100 as an endogenous emulsifier. The dissolution of the active ingredient from Eudragit NE-coated samples during storage is known to undergo a change. The crystallization of the emulsifier agent can play an important role in this. This polymer is not soluble in the gastrointestinal tract, but is permeable. Various parameters can influence the permeability of this film, e.g. via the tensile properties of the film. Change in the film thickness can cause the stretching of the film on a solid surface. Alterations in this physical parameter of the film were measured and the effects of different storage conditions were evaluated. The free film was prepared by spraying onto teflon. The crystallization of nonoxynol was followed via the changes in the DSC curve of the free film. A relationship was found between the film thickness and the crystallization of nonoxynol. It was established that the different storage conditions influence these changes. The temperature and the air humidity are important in this phenomenon. Lengthening of the storage time increased the difference in film thickness and crystallisation of emulsifier. This revised version was published online in July 2006 with corrections to the Cover Date.     

Study of the Effect of an Antifoaming Agent on the Evaporation of the Components During the Stirring of a Coating Dispersion Containing a Volatile Agent

The main objective of this work was to evaluate the evaporation of coating liquids containing a volatile component (ethanol) and an aqueous polymer dispersion under well‐controlled circumstances. The influence of different concentrations of a polydimethylsiloxane type antifoaming agent was studied. In consequence of to its low interfacial tension, it can form a layer on the surface of a liquid, and the effect of this was studied by determination of the quantity of the stirred liquid that was evaporated. The effects of different operational factors were compared by means of factorial designs. It was conluded that the presence of ethanol in the liquid changed not only the extents of the effects of the factors, but also their relative importance as concerns the evaporation process. The highest difference in effect of a given factor was detected for the stirring rate, while the lowest difference was observed for the duration of stirring. A high concentration of Dimeticon decreased the extent of evaporation, but not significantly. Thus, the alterations in the effects of the operational factors were not very substantial either. It may be stated that this antifoaming agent does not result in a relevant change in the evaporation in these systems containing ethanol as a volatile component. Accordingly, primarily the operational parameters must be considered during the formulation of these compositions. This information helps towards the design of an appropriate stirring device, because our results indicate that open systems are not adequate and it is known that hermetically closed tanks make atomization impossible. Hence, determination of the critical control points of coatings with a liquid containing a volatile component cannot be avoided because the vapour of such materials can be very dangerous.     

Effect of plasticizer on surface of free films prepared from aqueous solutions of salts of cationic polymers with different plasticizers

Acquisition of a more detailed understanding of all technological processes is currently a relevant tendency in pharmaceutical technology and hence in industry. A knowledge of film formation from dispersion of polymers is very important during the coating of solid dosage forms. This process and the structure of the film can be influenced by different additives. In the present study, taste-masking films were prepared from aqueous citric acid solutions of a cationic polymer (Eudragit^® E PO) with various hydrophilic plasticizers (glycerol, propylene glycol and different poly(ethylene glycols)). The mechanical properties, film thickness, wetting properties and surface free energy of the free films were studied. The aim was to evaluate the properties of surface of free films to predict the arrangement of macromolecules in films formed from aqueous solutions of salts of cationic polymers. A high molecular weight of the plasticizer decreased the work of deformation. The surface free energy and the polarity were highest for the film without plasticizer; the hydrophilic additives decreased these parameters. The direction of the change in polarity (a hydrophilic component caused a decrease in the polarity) was unexpected. It can be explained by the change in orientation of the macromolecules, a hydrophobic surface being formed. Examination of the mechanical properties and film thickness can furnish additional results towards a knowledge of film formation by this not frequently applied type of polymer from aqueous solution.