A new method to evaluate the consolidation behavior of pharmaceutical materials by using the Fraser-Suzuki function.

A new method was developed to evaluate the consolidation behavior of different pharmaceutical materials. A method to evaluate the elastic deformation of the different parts of the tablet machine is described. The used model is based on the Fraser--Suzuki function, which was modified to fit the force-time course. This function has three parameters, which describe the consolidation behaviour of pharmaceutical materials. Parameter A (form of the increasing part of the force-time course) and tr parameter (time of force maximum) give qualitative evaluation of the irreversible deformation during the compression process. Parameter S (form of the decreasing part of the curve) describes the decompression phase and provides information about the elastic behaviour of the compressed material. In this article, the importance of the different parameters is presented. The applicability of this function to different kinds of ethylcellulose is also presented.

The effect of ethylcellulose molecular weight on the properties of theophylline microspheres.

Microspheres of theophylline, with both ethylcellulose of high and low molecular weight and also their mixtures as a coating material, were prepared using the solvent evaporation technique. No permeability through intact isolated polymer films was found. Therefore, this study investigated the drug release dependence of structure and mechanical properties of the polymer matrix. In vitro dissolution studies exhibited the square-root of time (Higuchi model) release characteristics. The size distribution of microspheres was dependent on the ratio of ethylcellulose mixtures with high and low molecular weights.

[The crystallography behavior of carbamazepine under compression pressure]. / Zum kristallografischen Verhalten des Carbamazepins unter Pressdruck.

In the present paper the crystallographic behavior of the carbamazepine modifications I, II and III were studied under various conditions by means of X-ray powder diffraction, IR-spectroscopy and differential-scanning-calorimetry. It was found that the crystal lattice of the carbamazepine modification I is relative stable to the applied pressure forms, whereas modification II under similar conditions undergoes a polymorphic transformation into carbamazepine modification III, the extent of which depends on compression pressure and storage time of the tablets. In the compression samples of carbamazepine modification III neither IR-spectroscopically nor X-ray-diffractionally an influence of the pressure could be found on growing up of the enantiotrophic modification I.

[Phase transformation of carbamazepine by the milling process]. / Modifikationsumwandlungen des Carbamazepins durch Mahlprozesse.

In the present paper the interconversion behavior of the carbamazepine modifications I, II and III under various grinding conditions (variation of milling aggregates, milling times and frequencies) were studied. Mechanical treatment of different crystal forms led to a uniform grinding product, which is characterized crystallographically as modification III. The kinetic of phase transformations were determined by means of various quantitative methods such as a IR-spectral, a X-ray-powder diffractional and a thermoanalytical one. The results obtained by different analytical methods accorded quite well.

[Preparations of matrix tablets from a polyacrylate base]. / Darstellung von Matrixtabletten auf der Basis von Polyacrylaten.

The authors report with the example of the model drug, caffeine, on the preparation and investigation of matrix tablets on the basis of acrylates. The release values obtained were analysed by the equations of Higuchi and also Noyes-Whitney. It was demonstrated, that the polymer composition and the drug content in the tablets have an influence on the release of the drug.

[The control of drug release of heavy-soluble, weak basic drugs in matrix tablets using the example of medazepam]. / Zur Steuerung der Arzneistofffreigabe schwerlöslicher, schwach basischer Arzneistoffe aus Matrixtabletten am Beispiel von Medazepam.

According to ideas about the diffusion layer in the process of dissolving solids the release of medazepam as a model substance for heavy-soluble, weak alkaline substances is modified by incorporation of solid acids of different solubility and dissociation rate into the matrix. The determination of the solubility and a "virtual" pH-value within the matrix tablets leads to the evaluation of the liberation. A relatively continuous release of medazepam following different pH-values in the medium was obtained by microencapsulation of the citrus acid incorporated. Using the ideas of the diffusion layer to explain the conditions within the matrix it becomes possible to control and influence the drug release from the matrix tablet.

[The determination of the Enslin number]. / Zur Bestimmung der Enslin-Zahl.

An apparatus after Ezersky was used for the determination of the Enslin number, thereby some error possibilities mentioned in the literature were investigated and compared with the method after the 2. AB-DDR. The dependence of the Enslin number on the height of the powder bed was proofed also at little layer thickness of some substances. The error possibilities are: tending of the powder bed by burning of the lower wet part, occurring of air bubbles below the powder bed and also the capillary action directed against the incorporation at the tip of a completely filled graduated pipet. The apparatus after the 2. AB-DDR as the apparatus after Ezersky, especially with graduated pipet without tip, produced measuring values with little deviation. The latter apparatus allowes a more rational using.

[Construction, operation and initial experience with a laboratory apparatus for fluid-bed coating of particles]. / Aufbau, Arbeitsweise und erste Erfahrungen mit einem Laborgerät zum Uberziehen von Partikeln in der Wirbelschicht.

Starting from the developmental work of Dittgen and co-workers [1] and of Gröning [2], the authors constructed an air-suspension device which permits to coat crystals, granules and pellets on a laboratory scale. The device developed is a glass apparatus for coating almost 10 g of particles. The motion of the particles to be coated is characterized by a high-speed rotation on a circular orbit associated with a raise by the air current and a fall caused by gravity. This combined motion prevents the development of zones of varying particle sizes. The usefulness of this apparatus is demonstrated by the example of the application of a polyacrylate depot coating to pholedrine sulphate and quinidine sulphate pellets. Scanning electron micrographs are used for the optical assessment of the coating.

[On the production and the characterization of spray embeddings (author's transl)]. / Zur Herstellung und Charakterisierung von Sprüheinbettungen.

Spray drying of phenobarbital-polyvinyl pyrrolidone (PVP), phenobarbital-polyvinyl alcohol (PVA) and digoxin-PVP solutions yielded embeddings in the form of very fine powders. Depending on the drug-adjuvant ratio, the form in which the drug was embedded in the indifferent carriers was microcrystalline to radio-amorphous. In vitro studies showed that the dissolution of all the spray products was more rapid than that of the corresponding physical mixtures, and that the resulting solutions of the respective drugs were always oversaturated. The oversaturated solutions obtained from embeddings containing the amorphous forms of the difficulty soluble drugs were relatively stable. PVP inhibited the crystallization of phenobarbital to a greater extent than PVA, and led to a higher oversaturation of the drug in the resulting solutions. The in vitro release of digoxin was significantly more rapid from PVP embeddings (and tablets made from them) than from products containing digoxin in crystalline form.

[The use of spray drying in pharmacy (author's transl)]. / Anwendung der Spühtrocknung in der Pharmazie.

Owing to the favourable physical conditions of the evaporation process, the technique of spray drying has been used for some time to obtain dried products from solutions, suspensions, emulsions and fluid extracts. In the pharmaceutical industry, it may be utilized as a -drying technique, -micronizing procedure, -procedure for the manufacture of polymorphic or amorphic forms of active substances, -technique for producing microcapsules and spray embeddings, -method for manufacturing direct-tablettable active substances. The technical development which ranges from spray dryers for laboratory experiments to industrial plants, and the continuous operation are favourable prerequisites for research and use on an ever greater scale.