POWDER LAYERING IN SOLID WALL PAN FOR FAST PREPARATION OF SUGAR SPHERES

Sugar spheres (also called neutral pellets, nonpareil seeds, microgranules or sugar beads) are inert cores mainly based on sucrose and starch, used as excipients for sustained-release oral solid dose formulations. Sugar spheres are aimed to be coated by active ingredient up to 75% of drug layering; the properties that have been identified as critical to successful drug loading are surface roughness and sphericity, particle size and its distribution, density, friability and hardness. As reported in the USP and EP harmonised monographs, sugar spheres mainly consist of sucrose and starch and may contain colours additives permitted by the FDA for use in drugs. Two technologies are mainly used for the preparation of sugar spheres both starting from raw sugar crystals: sucrose layering as liquid syrup (liquid layering) and sugar powder layering (powder layering). In the first case the process is longer but the use of syrup enables the surface smoothness and spherical shape. By using the powder layering method, process time can be more cost effective however great attention must be paid to the parameters in order to obtain regular shape. Aim of the study was to evaluate the possibility of manufacturing sugar spheres in pilot solid wall pan (IMA GS HP 25 litres) by using the powder layering method and at the same time to obtain spheres with good technological properties. For comparison purpose in terms of process time and particle size two batches of sugar spheres were manufactured by liquid layering in the same equipment. Sugar crystals (10 kg, particle size corresponding to 90% lower than 200 micron) was used as starting material in all trials. Liquid layering was performed by repeating several times a cycle of spray, pause and drying; during the spray step a syrup made of sucrose 52,3%, corn starch 22% and water 25,7% was employed. The syrup was kept at 65°C for the entire process. Powder layering provided several repetition of spray, pause, powder, pause and drying; the same syrup composition as the liquid layering (same T°) was sprayed as binder while micronized sugar powder was applied using a screw feeder without the need of any flowability enhancer excipients. For both methodologies the end of the process was individuated when reaching the target sugar spheres particle size and a loss on drying lower than 4%. Morphology, flowability and friability were tested. The liquid layering trials provided, as expected, spherical sugar spheres with good technological characteristics but the process time to pass from raw sugar to a final product having d90 between 300 and 800 microns was approximately 16 hours. The first trials by applying sucrose in powder allowed to obtain sugar spheres having the same size as for the liquid layering process shorten the process time up to 3 hours; however the process did not lead to sugar spheres with acceptable sphericity and smooth surface. The subsequent experiments focused on optimising the process parameters (in particular spray quantity, pause time, powder quantity, cores temperature and pan speed) in order to improve sugar spheres morphology. The best result was obtained by using the following parameters: inlet air 180 m3/h at 70°C, pan negative pressure – 10 Pa, cores temperature in the range 35 - 38°C, pan speed 22 rpm, spray pressure 1 bar, recycling pressure 0,8 bar, spray time gradually increasing from 7 to 21 seconds (spray rate 8 g/sec), powder addition time time gradually increasing from 7 to 36 seconds (powder delivery rate 16 g/sec using screw feeder at 120 rpm), pause time after spray and powder between 30 and 60 seconds, drying time 60 – 90 seconds. The product obtained resulted in consistent technological properties. In conclusion, the results presented in the study evidenced that sugar powder layering in solid wall pan is a suitable technology to manufacture sugar spheres having morphology and technological properties ideal for the following drug layering in a short pro...