The study of the kinetic of natural zeolite granules growth at different ways of granulation

Abstract

Introduction. Active substances and excipients used in the manufacture of medicines in tablet form, in most cases, have poor technological properties. This fact determines the need for prior granulation of mass before compression. Granulators of various sizes and designs, running on different modes, made the formation, growth and consolidation of the powder particles that lead to obtain pellets of different shapes and sizes. From the literature it is known that granulation leads to two forms of granules: isodiametric and nonisodiametric. The first group of particles forms has globular shape with a smooth surface and the proportion in which the length, thickness and height are about the same. They are usually made by fluidized bed granulation, spray drying, pelletizing and granulation in dragee pan. Granules of nonisodiametric form in which length is several times the width and height are made mostly by extrusion and compacting. The geometrical parameters of obtained granules are affected by the properties of raw materials, the granulation modes, type and amount of added humidifier and so on. The shape and size of granules, from a technological point of view, are the key factors that contribute, except organoleptic characteristics of the product, its technological properties such as particle size distribution, bulk volume, the ability of the material to shrinkage, porosity, fluidity, mechanical strength and so on. Properly selected for specific conditions granulation method is able to provide the finished product with the specified technological parameters depending on the needs. The aim of this work was to study the effect of granulation method and its conditions on the kinetics of growth of the natural zeolite granules and some quality characteristics of obtained granules. Material & methods. As objects of study served the natural zeolite pellets produced using 3%, 5%, 7% and 10% potato starch paste and solution of polyvinylpyrrolidone (PVP). Natural zeolite granules were prepared by wet granulation using a laboratory rotary granulator NG-12, laboratory extruder, laboratory high-speed mixer-granulator and laboratory dragee pan NSD A-0.25. Microstructure and form of granules were established by electron microscope REM-106. Fractional composition and average grain size was determined using a standard set of sieves with the diameter of the holes 2.0; 1.0; 0.5 and 0.25 mm. Porosity determined on the basis of tapped density and the real density, which were defined on the device Pharma Test PTF PT-TD200, Germany by the method. Form factor calculated as the ratio of the share of grains in its width. The hardness of the granules was assessed by their ability to withstand compression. Results & discussion. The resulting granules have heterogeneous porous surface. Granules obtained using rotary granulator and extruder have elongated form of particles with form factor 1,6-1,7 and 2,5-2,8 respectively. Granules obtained in high speed mixer-granulator and dragee pan have nearly round shape with form factor 1.1-1.2. The size of the granules is affected by the concentration of the humidifier and the way of granulation. The increasing of concentrations of potato starch paste from 3% to 10%, lead to an increase of the average size of granules according to the method in average 3-5 times, the last was proved by the increase of fractions with a larger particle size. The largest average size of granules was obtained in the laboratory dragee pan, and the smallest - in the high-speed mixer-granulator. When using PVP solution of different concentrations the average grain size varied depending on the method of granulation within 120-1464 µm. The highest binding capacity showed PVP solutions, as evidenced by higher values of grain size at the same concentrations of humidifiers. Increased concentrations of both humidifiers more than 10% is inappropriate, because results in large particle size of granules. Study of influence of quantities of added humidifier on grain size showed that the granulation process is absent in mixtures containing humidifying substance in quantities of 15-20%. The best concentration of humidifier should be 25-30%, which give granules with an average size of 450-1350 µm, and a further increase of its content results in a viscous mass that is difficult granulated and undesirable. Experimental data of granule porosity indicates that increasing the concentration of binders increases porosity within 50-70%. The influence of granulation mode on porosity of both substances is different. The data of hardness of granules showed that this parameter is in inverse proportion to their porosity. Pellets made with using PVP solution demonstrated greater mechanical strength compared to granules containing starch potato paste. Conclusion. The influence of type and concentration of the humidifier and the method of granulation on the kinetics of growth of the natural zeolite granules were studied and its influence of these variables on the size, porosity and mechanical strength of the pellets were proven. The optimum concentration of potato starch paste and solution of polyvinylpyrrolidone as binders for granulation of natural zeolite at level 5-10% and optimal content of humidifier in the total mass at level 25-30% were established. The results of experimental studies used in the development of technology and composition of  tablets containing natural zeolite as the main active component.