[Real-time monitoring of drug crystallization with and without additives]. / Gyógyszerhatóanyag-kristályosodás valós ideju vizsgálata és módosítása segédanyaggal.

Crystallization processes can be evaluated from both kinetic and thermodinamic point of view with real-time analitical methods, effects of production parameters on the final quality can be estimated as well. Consequently there is an increasing emphasis on analytical devices being applicable for real-time detection. Among these techniques Raman spectrometry is advantageously utilizable for real-time monitoring of crystallizations. Impurities can dramatically change the nucleation and crystal growth, thus they can alter the physical and chemical properties of the final product. The use of different additives (polymers;surface active ingredients) in the crystallization step in order to modify the product morphology methodically is a new direction in the scientific literature. This study provides an overview of crystallization processes in the presence of additives as well as a summary concerning the monitoring of the drug crystallizations by real-time Raman spectrometry. Furthermore the effect of polyvinyl-pyrrolidone was examined in the course of cooling crystallization of Donepezil HCl, while the process was monitored by in-line Raman spectrometry.

Characterisation of the large-scale production process of oyster mushroom (Pleurotus ostreatus) with the analysis of succession and spatial heterogeneity of lignocellulolytic enzyme activities.

Oyster mushroom (Pleurotus ostreatus) lignocellulolytic enzyme activity pattern and variation was investigated in a large-scale facility from spawning until the end of the second flush. In the first cultivation cycle laccase production reached its peak during vegetative growth stage, while manganese-peroxidase showed the highest activity during fruiting body induction. Cellulose and hemicellulose degrading enzymes had maximal activity at the beginning of flush and harvest stage. The enzyme activities showed similar tendencies among five different mushroom substrate blocks representing a production house. The spatial variability analysis of enzyme activities pointed out the within substrate block heterogeneity as the main source if variation. This result was confirmed by Combined Cluster and Discriminant Analysis (CCDA) method showing minimal among block heterogeneity considering the whole investigation period; furthermore in the first cultivation cycle all blocks were grouped into one cluster.

Predicting final product properties of melt extruded solid dispersions from process parameters using Raman spectrometry.

Raman spectrometry was utilized to estimate degraded drug percentage, residual drug crystallinity and glass-transition temperature in the case of melt-extruded pharmaceutical products. Tight correlation was shown between the results obtained by confocal Raman mapping and transmission Raman spectrometry, a PAT-compatible potential in-line analytical tool. Immediate-release spironolactone-Eudragit E solid dispersions were the model system, owing to the achievable amorphization and the heat-sensitivity of the drug compound. The deep investigation of the relationship between process parameters, residual drug crystallinity and degradation was performed using statistical tools and a factorial experimental design defining 54 different circumstances for the preparation of solid dispersions. From the examined factors, drug content (10, 20 and 30%), temperature (110, 130 and 150°C) and residence time (2.75, 11.00 and 24.75min) were found to have significant and considerable effect. By forming physically stable homogeneous dispersions, the originally very slow dissolution of the lipophilic and poorly water-soluble spironolactone was reasonably improved, making 3minute release possible in acidic medium.

Comparison of electrospun and extruded Soluplus®-based solid dosage forms of improved dissolution.

Electrospinning (ES) and extrusion of a poorly water-soluble active pharmaceutical ingredient were used to improve its dissolution, which is a major challenge in the field of pharmaceutical technology. Spironolactone was applied as model drug and recently developed polyvinyl caprolactame-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®) was used as carrier matrix and solubilizer. ES of the polymer matrix from ethanol solution was optimized at first without spironolactone and then the cosolution of the drug and the carrier was used for forming electrospun fibers. It resulted in real solid solution due to its very efficient amorphization effect. On the contrary, a low amount of crystalline spironolactone appeared in the extrudates according to Raman microscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy-dispersive spectrometry (EDS). Raman microspectrometry had the lowest detection limit of spironolactone crystals compared with XRD and differential scanning calorimetry. Both ES and extrusion techniques resulted in significantly improved dissolution. Electrospun ultrafine fibers increased the dissolution more effectively, owing to the formed solid solution and huge surface. The developed continuous technologies demonstrate great potential to tackle the challenge of inadequate dissolution of poorly water-soluble drugs in several cases.