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Pulmonary drug delivery (PDD) has potential for both local and systemic therapy. Our research group is focus- ing on the development of dry powder inhalation (DPI) systems for PDD due to their beneficial properties. Although there is not yet a marketed inhalation product for non-steroidal anti-inflammatory drugs (NSAIDs), their therapeutic use in sev- eral lung diseases is well established and successful DPI developments have been performed with them. Sodium stearate (NaSt) is a promising excipient for DPI development, but its role in NSAIDs has not yet been investigated. Thus, the aim was to study DPI samples produced by co-spray-drying, applying meloxicam potassium (MXP) as an NSAID drug, and different concentrations (0-2 w/w%) of NaSt. Physicochemical investigations, in vitro lung deposition, and in vitro drug release measurements were performed. It can be stated that co-spray-drying of MXP with NaSt resulted in remarkable morphological differences by increasing the concentration of NaSt, which had a positive effect on cohesive work. Further- more, applying of NaSt accelerates the dissolution in simulated lung fluid (SLF). NaSt as excipient has a future for the formulation of the DPI systems because there are in the development focus the attaintment of the higher FPF values and improvement of dissolution in SLF.

Drug administration through the nose offers great possibilities which have been discovered in the past few decades. Besides the most known local effect, systemic and central nervous system effect is also available, the administration is non-painful and the degradation effect of the gastrointestinal tract can be avoided. Amongst the nasal formulations, powders have become more popular as their stability is favorable compared to the liquid formulations and a higher dose can be administered in powder form. The quality insurance and stability of the products in the pharmaceutical field have gained considerable attention in the last decades. Due to this fact, the aim was to execute a long-term stability study of a previously developed, nanosized lamotrigine (LAM) containing nasal powder (NP) formulation. The results of the stability test showed that the NP formulation preserved its key properties (particle size, morphology, structure and in vitro drug release) after 6 months of storage.

Nowadays the nasal route has received a great attention as a reliable administration for the systemic administration. In the Department of Pharmaceutical Technology, University of Szeged, the main research work is the design and development of innovative nasal formulations, which can open new possibilities for some well-known agents and may also help some drug-candidates delivery problems. The aim of this work was to present some reliable models for investigation of permeability, such as Spectra/Por Dialisys Membran, ZelluTrans/Roth Mini Dialyzer, μFLUX diffusion Cell, Navicyte Vertical and Horizontal Diffusion Chamber System and In-line Cell. In addition, the horizontal membrane diffusion model (Side-Bi-Side) was used to investigate in vitro and ex vivo studies of permeability of meloxicam in comparison with the vertical diffusion cell (Franz). The present study investigated the meloxicam in different dosage forms (powder, spray, gel). It was found that the Side-Bi-Side cell is suitable to test the nasal formulations, but the uniform distribution of the active substance cannot be ensured in donor place by increasing the viscosity of the compositions, therefore the Franz cell is recommended for investigation of nasal gel. Previous measurement cannot be found related to this topic.

In our work, the effect of crystallization methods and their parameters on the particle size, particle size-distribution and roundness were investigated in case of glycine crystallization. Three types of crystallization methods were applied according to the solubility results of the substance. In case of cooling crystallization, the effect of cooling and stirring rates were investigated. The feeding and stirring rates were changed in the feeding crystallization. In the antisolvent technique, the effect of cycle and amplitude of the sonification were studied on the particle size. A 3(2) full factorial design was applied for investigation of the effect of crystallization parameters. The results were analyzed by statistical software. The particle size distribution and roundness were measured by laser diffraction and light microscopic image analysis systems. The polymorph type of products was investigated by XRPD. The crystallized product morphology was examined using scanning electron microscopy. We found that the crystallization methods and certain parameters have significant effect on the particle size, particle size distribution. In spite of the modified particle size, morphology, roundness, the polymorph type of the product was the same with the original material.

The main aspect in the field of pharmaceutical technology is the preformulation of the poorly water soluble drugs. The habit of particles can effect the physico-chemical properties which are important factors by drug administration. In the past years the role of the procedures by acustic cavitation increased in the field of particle engineering. Application of high power ultrasound by integration and dezintegration can lead to particle size decreasing. Meloxicam as a nonsteroid anti-inflammatory model drug was used to study the effect of power ultrasound on the particle size decreasing. During our work technological parameters, as amplitude, temperature, time, excipients and concentration were optimized based on particle size distribution. Physico-chemical stability tests were also performed (XRPD, DSC, SEM, particle size). With optimized parameters (70% amplitude, 20 min, 47 0C) using excipients, crystalline micronized product was produced.

Nowadays, one of the most important task of the pharmaceutical technology is to optimize the dissolution of active ingredients, because most of the drug candidates have a poorly water solubility and hence a slow absorption. According to the latest examinations, the bioavailability of poorly water soluble drugs can be increased significantly by using surfactants or the mixture of surfactants and polymers. Nowadays, surfactants (like polysorbates) are generally used in the production of solid dispersions, so the use of surface-active sucrose esters can be resulted an innovative solution in the pharmaceutical technology. The aim of our investigation was to examine the applicability of sucrose laurate in hot-melt technology in order to influence the crystalline structure and dissolution rate of a poorly water soluble drug (gemfibrosil) having low-melting point. The results of the X-ray powder diffractometry have showed that the sucrose laurate had no significant effect on the crystallization degree of the drug which is important in case of the stability. On the bases of the results of in-vitro dissolution studies, it can be concluded that the sucrose laurate (using minimum 5%) can be well applied in hot-melt technology with carriers having characteristic melting point (e.g. Macrogol) to increase the dissolution rate of poorly soluble drugs.

Present work provides a short review concerning the importance of particle size decreasing in the drug formulation. The presented theoretical introduction collects the must important factors which influence the dezintegration and integration mechanisms. Modification of particle size and morphology could overcome the formulation problems, resulted improved drug release. Wet milling and solvent diffusion, as a novel methods to complete with drying will be presented applying the poorly water-soluble niflumic acid. Differences in particle sizes were found according to the used processing. The specific surface area of the drug was increased following particle size reduction and the dissolution rate was therefore significantly improved. During structural characterizations (DSC and XRPD), strong interactions were detected between the drug and stabilizer.

One of the most important task of the pharmaceutical technology is to reach a possible high gastrointestinal absorbtion of the active ingredient. Therefore, it is necessary to have a good solubility in the gastric/intestinal medium. In this way the applied drug quantity and unwanted side effects can be reduced with solubility increasing. The water-insoluble drug's solubility and bioavailability can be increased by the alteration of their physicochemical properties. Nifluminic acid is a frequently used anti-inflammatory drug with low aqueous solubility. Inclusion complexation with cyclodextrins is an efficacious method to improve the solubility, stability and bioavailability. Ternary systems were prepared and investigated to use nifluminic acid, hydoxypropyl-beta-cyclodextrin and polyvidone. The aims of the study were to investigate the solubility rate, the in vitro diffusion ability, to determine the n-octanol/water partition coefficient, and to study the thermoanalitycal properties of products. The results suggested that complexation with cyclodextrin and the use of polyvidone is better method than to prepare binary systems. Inclusion complexation was presumed in the event of the ternary composition to improve the bioavailability of nifluminic acid.