Drug layering in a perforated pan: impact of up-scaling on coating distribution uniformity

The growing interest in incorporating an active ingredient in the coating formulation requires that both process and equipment ensure uniform distribution of the coating material. Up to date the majority of the papers refers to optimisation of drug layering on cores in pan applied to small or pilot scales. However it is crucial for the pharmaceutical industry to be sure that the coating uniformity is maintained and guaranteed also in the production scale. The aim of this work was to achieve uniformity of coating distribution on both pilot and production equipments; two different pan loading (medium and maximum) were considered on both scales. Placebo oblong tablets (density 0.8 kg/L) providing mean weight of 850 mg were used as substrate for the drug layering. Tablets were coated in both pilot (Perfima Lab 30 litres, IMA) and production scale (Perfima 200 litres, IMA) using a water based coating formula containing Riboflavine as a drug tracer and Methocel E5 and PEG 6000 as polymer and plasticizer respectevely. The target weight gain was 10% by weight. For all batches the coating distribution uniformity was determined calculating the coating Relative Standard Deviation (RSD) that has to be lower than 6% as reported in literature. In addition the coating thickness was assessed by Scanning Electron Microscopy (SEM) and the Riboflavine content was analysed by the HPLC method. Coating losses were also calculated for all batches. In the preliminary part of the study 10 batches were performed on pilot equipment to identify the critical process parameters (process time, pan speed, atomisation pressure, gun distance, pan loading) affecting the uniformity of coating distribution. The results showed that the optimal parameters combination obtained for both medium (12kg) and maximum (25 kg) pan loading allowed to obtain a good coating distribution as demonstrated by the coating RSD values always lower than 6%. Coating losses resulted 10,8% and 11,5% for 12 kg and 25 kg respectively. Up-scaling the drug layering process, two batches of 125 kg (medium pan loading) and 160 kg (maximum pan loading) were produced. The results showed that utilising the atomisation pressure, gun distance and total process time equal to the pilot scale batches and modifing the inlet air temperature, inlet air temperature quantity, pan speed and number of guns, the coating uniformity was mantained.%2