Pharmaceutical tablet coating variability: Variation of tablet residence times and coating optimization.

A successfully coated batch of pharmaceutical tablets will have a prescribed coating thickness on each tablet's surface with little inter- and intra-tablet variability. Variability needs to be minimized for functional coated tablets, since the amount of coating controls the release profile and bioavailability of the drug. Large variations in coating thickness can adversely influence the effectiveness of the tablet. Uncoated tablet batches are placed within horizontal rotating pans with the coating solution sprayed onto the surface of the rolling tablet bed. The coating process is terminated when the prescribed amount of coating is sprayed onto the tablet bed. For minimum inter-tablet coating variability, the variation in tablet-to-tablet spray zone residence time should be reduced, since the amount of coating deposited on the tablets is directly related to the residence times. The current work investigates inter-tablet coating variability of spherical tablets in a horizontal axis pan coater using the discrete element method. Measurements of the fractional residence time, defined as the ratio of time spent by a tablet in the spray zone to the total coating time, are made for five tablet batch sizes and seven pan rotational speeds. The discrete element computer simulations suggest that average fractional residence time is independent of pan speed and total coating time for spherical tablets and is equal to the ratio of the number of tablets exposed to the spray to the total number of tablets, referred to as the coating fraction. Independently deduced analysis and video experiments supports the discrete element computer simulation results. While the average fractional residence time determines the average amount of coating received by a tablet, it is the variability in residence times that controls the amount of variability in the coated batch of tablets. Analytically, coefficient of variation of fractional residence time is proportional to the -1/2 power of the number of coating “trials” in a randomly coated batch of tablets. A coating trial occurs over an interval of time where the tablets in the spray zone and the tablets outside the spray zone appear to be segregated, i.e. not mixed. For extremely small intervals of time the tablet bed appears static and unmixed, as the tablets have not had sufficient time to move into new positions. For very large intervals of time the tablet bed appears to be well mixed and tablet positions appear to be randomly distributed in space with respect to the original reference state. The critical interval of time is the largest time interval where the tablets in the spray zone can be considered to be segregated from the tablets outside the spray zone. Physically this is approximately equal to the time taken for the spray zone to be populated with a new set of tablets that previously lay outside the spray zone and is equal to the time per coating trial. Decreasing the time per coating trial reduces inter-tablet variability as it increases the number of coating trials. The time per coating trial can be decreased by increasing pan speed, increasing the spray zone aspect ratio (spanwise-to-streamwise spray zone dimension), choosing an optimal tablet load that minimizes slumping motion (rigid body motion) in the tablet bed and increasing tablet-pan and tablet-tablet friction coefficients. Analysis independent of the discrete element simulations suggests a ways to optimize inter-tablet coating variability by controlling average fractional residence time, and the time per coating trial, ensuring only an allowable fraction of tablets is over- or undercoated.