Authors:P. Sipos, A. Szabó, I. Erős, and Piroska Szabó-Révész
A study was made of the possibilities of gradually decreasing the concentration of the toxic organic solvent in the process
of microsphere preparation. Ammonio methacrylate copolymer-based microspheres were prepared by spray drying or conventional
solvent evaporation techniques, and compared. The formulations were designed by varying the preparation methods and the concentrations
of four polar cosolvents as independent variables.
DSC was used to study the relationship between the changes in the independent variables and three of the main thermal events
of the microspheres. Raman spectroscopy was used to investigate and confirm the possible interactions between drug and copolymer.
Appropriate choice of the independent variables led to the molecularly dispersed drug in the polymer matrix. It was demonstrated
that only the nature of the preparation method caused significant variations in the structure and thermal behaviour of the
Authors:G. Sohár, E. Pallagi, P. Szabó-Révész, and K. Tóth
Osteoarthritis, although classically conceived of as a degenerative consequence of aging, is a disease with an increasingly
well-characterized molecular pathophysiology. Pathologic changes in cartilage composition and molecular organization, as well
as elevated water content, alter the exquisite balance of biomechanical properties. Much of what is known about changes in
the extracellular matrix in osteoarthritis comes from animal models.
Previously, thermogravimetric methods have not been used for compositional thermoanalytical study of normal and degenerative
human hyaline cartilage. For this reason the research group established a sufficient new thermogravimetric protocol, which
proved water content elevation contributing to disease progression.
Authors:Á. Gombás, P. Szabó-Révész, G. Regdon, and I. Erős
Mannitol and sorbitol are widely used in the pharmaceutical and food industry. There are some technological procedures such
as spray-drying, freeze-drying, tablet compression, during which there is a possibility of heat effect. The purpose of this
work was to study the thermal properties of sorbitol, mannitol and their mixtures. Furthermore, these materials and their
tablet pressing were studied after melting and solidification. The results of the study prove that the use of sorbitol or
mannitol alone is disadvantageous in melt technology. The use of mannitol is limited because of its high melting point (165C)
and the polymorph transition after melting. Sorbitol (melting point: 96.8C) vitrifies from melt, therefore it is hard to
handle during further processing. The melting point of the eutectic mixture (1.8% mannitol and 98.2% sorbitol) was 93.6C.
This mixture was unsuited for pressing because of its glassy property. Our results showed that the most favourable composition
was the mixture of 30% mannitol and 70% sorbitol (melting point: 131.8C) for tablet formulation. This mixture can be recommended
for the formulation of such lozenge and hard candy tablets, where the active ingredient decomposes at higher temperature (>131.8C).
Authors:Á. Beretzky, P. Kása, K. Pintye-Hódi, J. Bajdik, P. Szabó-Révész, and I. Erős
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.
Authors:J. Bajdik, K. Pintye-Hódi, G. Regdon, P. Fazekas, P. Szabó-Révész, and I. Erős
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.
Authors:J. Bajdik, K. Pintye-Hódi, Cs. Novák, P. Szabó-Révész, G. Regdon, I. Erős, and G. Pokol
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.
Authors:Á. GombÁs, P. Szabó-Révész, M. Kata, G. Regdon, and I. Erős
In pharmaceutical practice it is important and useful to know the crystallinity of materials and to monitor it during formulation
development, production processes and storage. The purpose of this study was to assess the quantitative capability of DSC
for determining crystallinity in crystalline/amorphous powder mixtures and to compare the accuracy of the DSC method with
that of conventional powder X-ray diffraction. Alpha-lactose monohydrate was chosen as the model material. On the basis of
this study it can be concluded, that DSC method can be applied safely for semiquantitative evaluation of the crystallinity
of lactose samples consisting of an amorphous content higher than 20%.
Authors:R. Ambrus, Z. Aigner, L. Catenacci, G. Bettinetti, P. Szabó-Révész, and M. Sorrenti
In view of the poor aqueous solubility of nifluminic acid (NIF), the aim of this article was to improve its solubility and dissolution rate through the preparation of formulations based on hydroxypropyl β-cyclodextrin (HPβCD) and polyvinylpyrrolidone K25 (PVP K25), a combination of carriers which has been advantageously used for a similar purpose with various hydrophobic drugs. Ternary systems of NIF, HPβCD, and PVP K25 were prepared in different drug to CD to PVP ratios by physical mixing, kneading, microwave irradiation, and co-evaporation. Differential scanning calorimetry, thermogravimetric analysis, hot stage microscopy, Fourier transform infrared spectroscopy, and X-ray powder diffractometry were used to investigate the resulting solid-state interactions. The results showed that the solid state of the drug in the amorphous or crystalline ternary combinations influenced both the solubility and the dissolution rate of NIF.
Authors:Z. Aigner, R. Heinrich, E. Sipos, G. Farkas, A. Ciurba, O. Berkesi, and P. Szabó-Révész
The compatibility of aceclofenac with various tableting excipients was investigated by means of differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). The excipients applied in the direct pressing retard tablets were Carbopol 940, hydroxypropyl-methyl-cellulose, microcrystalline cellulose, Aerosil 200 and magnesium stearate. The ingredients alone and their 1:1 (w/w) binary mixtures were investigated before and after accelerated storage. An interaction was observed only between aceclofenac and magnesium stearate. The DSC and FT-IR examinations indicated formation of the magnesium salt of aceclofenac. For the other mixtures, there was no incompatibility between the components.