Pellets are basis for multiple unit dosage forms and can be filled into hard capsules or pressed into tablets. They are often film coated with polymer film that can, among other functions, enable modified release of an active ingredient. Pellets do not have exactly the same size, but certain size distribution width. During manufacturing process differences in their size can lead to segregation, which means that pellets are separated into layers. During coating process differences in amount of received coating among pellets of different size can appear. This is especially unwanted, if the purpose of coating is to enable prolonged release of active pharmaceutical ingredient (API). In this case coating thickness and particles specific area have the biggest impact on release rate of API. In this master thesis we studied how the size of initial pellets affects final depth of coating in case of different design and size of fluid-bed coating equipment. We compared two versions of Wurster chamber that create different airflows and pellets movement and two heights of partition column. We evaluated their effect on release profiles of API from pellets with wider size distribution. After coating experiments we separated pellets by their size, determined the amount of incorporated API and carried out dissolution tests. When coating on pilot scale with swirl distribution plate and higher position of partition column, we managed to achieve that all pellet fractions yielded comparable release profiles; in case of lower position smaller pellets received disproportionally more coating than bigger ones, which even slowed down the release profile of the smallest pellets. On laboratory scale the differences in release profiles between classic and swirl distribution plates are small. Because of higher number of smaller pellets in the coating batch they received the same amount of coating compared to bigger pellets in case of classic coating chamber and even a little bit more in case of swirl version. In the second, complementary part of experiments we coated pellets with colouring agent and from particles coloring we extracted the coating thickness of individual pellets. From the slopes in coating thickness vs. pellet diameter diagram we found out that positive size dependent preference coating (bigger pellets receive more coating) is expressed in each series on laboratory scale, with a little bit lower slopes determined in experiments with swirl generator. From the obtained results we can generally conclude, that on both scales of swirl generator equipped coaters and in combination with selected process parameters, amount of pellets and particle size distribution the profile of deposited film coating on pellets of different size will be adequate regarding the compensation of differences in specific area of differently sized pellets, therefore quality of final product will not vary even in the case of potential segregation of pellet mixture.
|
