Abstract
In the present study the possibility of producing highly porous pellets of microcrystalline cellulose (MCC) was examined. High porosity is expected to reduce the density of pellets and affect the gastric emptying. Furthermore, it is expected to improve the loading ability. Initially were examined the effects of MCC type, of wetting liquid and drying method on the micromeritic, mechanical and disintegration properties of MCC pellets. Extrusion/spheronization was applied by using three types of MCC powder (Avicel®, Prosolv® and modified Avicel®) and two wetting liquids (water or water-isopropanol 60:40 w/w). Also, highly porous Avicel® pellets were prepared by the incorporation and extraction of pore former (NaCl). All the wet pellets were dried by employing three methods (fluidized bed, microwaves and freeze drying). It was found that the drying method has the greatest effect on the pellet size and porosity followed by the wetting liquid. Combination of water-isopropanol, freeze drying ...
In the present study the possibility of producing highly porous pellets of microcrystalline cellulose (MCC) was examined. High porosity is expected to reduce the density of pellets and affect the gastric emptying. Furthermore, it is expected to improve the loading ability. Initially were examined the effects of MCC type, of wetting liquid and drying method on the micromeritic, mechanical and disintegration properties of MCC pellets. Extrusion/spheronization was applied by using three types of MCC powder (Avicel®, Prosolv® and modified Avicel®) and two wetting liquids (water or water-isopropanol 60:40 w/w). Also, highly porous Avicel® pellets were prepared by the incorporation and extraction of pore former (NaCl). All the wet pellets were dried by employing three methods (fluidized bed, microwaves and freeze drying). It was found that the drying method has the greatest effect on the pellet size and porosity followed by the wetting liquid. Combination of water-isopropanol, freeze drying and modified MCC gave the greatest increase in pellet size and porosity. The increase in pellet porosity caused reduction in the resistance to deformation, tensile strength and disintegration time. Since the freeze drying caused the greatest increase on pellet porosity, the effects of initial freezing conditions (before the sublimation) on the pore volume and pore size distribution were evaluated. Freeze drying was applied after initial freezing under three different conditions (-30, -80 and -197 oC). Pellet porosity was found to increase with decreasing initial freezing temperature. The mean pore diameter was greater for the extracted pellets, followed by non extracted pellets made with water and water-isopropanol. Also, the pore diameter was greater for freezing at -80 o C while it was smaller at -197 o C. It was also noticed that the size of the pores formed by extraction of pore former is much smaller than that of pore former particles. This may be caused by the presence of “ink-bottle” pores. Therefore, pore shape of pellets was estimated by repeated mercury porosimetry and evaluation of mercury entrapment. From the mercury reintrusion it was found that the volumes of the second intrusion are considerably lower compared to the volumes of the first intrusion. Freeze-dried non-extracted pellets show lower formation of “ink-bottle” pores than fluidized bed dried pellets. Furthermore, water-isopropanol as wetting liquid results in higher “ink-bottle” percentage than water. The decrease of initial freezing temperature reduces the “ink-bottle” formation only when water is used as the granulating liquid. For the evaluation of drug loading ability as well as the release properties of porous pellets, MCC pellets with small pores or large pores were used. The pellets after loading by immersion in aqueous solution of riboflavin under vacuum and drying were coated with enteric and colonic coatings using methacrylic polymers. The requirements for effective gastroresistant coating and the release before and after coating were also evaluated. It was found that: a) The drug loading ability was higher for the pellets with large pores. b) The drug release from the non coated pellets was immediate, controlled by diffusion and faster for pellets with large pores. c) The required polymer dispersion for the effective gastro-resistance was higher for the case of pellets with large pores and the profile of drug release was delayed and reduced with the increase of the coating applied.
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