title: Modeling of pan coating processes: Prediction of tablet content uniformity and determination of critical process parameters.
abstract: We developed an engineering model for predicting the active pharmaceutical ingredient (API) content uniformity (CU) for a drug product in which the active is coated onto a core. The model is based on a two-zone mechanistic description of the spray coating process in a perforated coating pan. The relative standard deviation (RSD) of the API CU of the coated tablets was found to be inversely proportional to the square root of the total number of cycles between the spray zone and drying zone that the tablets undergo. The total number of cycles is a function of the number of tablets in the drying zone, the spray zone width, the tablet velocity, the tablet number density, and the total coating time. The sensitivity of the RSD to various critical coating process parameters, such as pan speed, pan load, spray zone width, as well as tablet size and shape was evaluated. Consequently, the critical coating process parameters needed to achieve the desired API CU were determined. Several active film coating experiments at 50, 200, and 400 kg using various pan coaters demonstrated that good correlation between the model predictions and the experimental results for the API CU was achieved.
authors.affiliation: Engineering Technologies, Process R&D, Bristol-Myers Squibb Co, New Brunswick, New Jersey, USA. wei.chen1@bms.com
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Shih-Ying
authors.initials: SY
authors.lastname: Chang
authors.forename: San
authors.initials: S
authors.lastname: Kiang
authors.forename: Alexander
authors.initials: A
authors.lastname: Marchut
authors.forename: Olav
authors.initials: O
authors.lastname: Lyngberg
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wang
authors.forename: Venkatramana
authors.initials: V
authors.lastname: Rao
authors.forename: Divyakant
authors.initials: D
authors.lastname: Desai
authors.forename: Howard
authors.initials: H
authors.lastname: Stamato
authors.forename: William
authors.initials: W
authors.lastname: Early
mesh_terms: D004339:Drug Compounding / Q000379:methods; D008956:Models, Chemical; D013608:Tablets, Enteric-Coated / Q000737:chemistry*
chemical_list: D013608:Tablets, Enteric-Coated