RESUMEN

Oral solid dosage forms that contain APIs in the amorphous state have become commonplace because of many drug substances exhibiting poor water solubility, which negatively impacts their absorption in the human GI tract. While micronization, solvent spray-drying, and hot-melt extrusion can address solubility issues, spray coating of the APIs onto beads and tablets offers another option for producing amorphous drug products. High-level comparisons between bead and tablet coating technologies have the potential for simpler equipment and operation that can reduce the cost of development and manufacturing. However, spray coating directly onto tablets is not without challenges, especially with respect to meeting uniformity acceptance value (AV) criteria, comprising accuracy (mean) and precision (variance) objectives. The feasibility of meeting AV criteria is examined, based on mathematical models for accuracy and precision. The results indicate that the main difficulty in manufacturing satisfactory drug-layered tablets by spray coating is caused by the practical limitations of achieving the necessary coating precision. Despite this limitation, it is shown that AV criteria can be consistently met by appropriate materials monitoring and control as well as processing equipment setup, operation, and maintenance.

RESUMEN

The relationships between coating uniformity and efficiency were explored for tablet coating processes in pan coaters. The factors affecting the size of the spray zone were modeled using one-dimensional deposition analysis of spray droplets. This model was incorporated into the analytical model developed for coating uniformity by Choi et al. (AAPS PharmSciTech 22(7), 2021) that farther elucidated the effects of tablet shape and bed porosity. The results were compared with literature data on coating efficiency. The variables examined included tablet shape and size, coating time, pan speed, atomizing and pattern air flow rates, bed porosity, spray rate, batch size, coating solution concentration, spray gun-to-bed distance, and pan diameter. It is shown that, except for pan diameter and atomizing air flow rate, variables that improve coating efficiency adversely affected coating uniformity and vice versa. Implications of these relationships are discussed to improve formulation, process, and equipment designs.

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RESUMEN

Novel mathematical models were developed to predict inter-tablet coating uniformity in terms of coefficients of variation (CV) and acceptance values (AV) for cylindrical tablet pan coaters, operating in batch and continuous modes. The models, based on binomial coating spray and tablet movement distribution functions and on bed geometry, yielded equations and results that are in good agreement with previously reported experimental data, most empirical expressions, and more computationally intensive models. The new model equations are readily useable for process analysis, optimization, scale-up, and manufacturing design and control.

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RESUMEN

The primary goal of this research was to determine the potential for denitrification and phosphorus removal of a full-scale sequencing batch reactor (SBR), with and without the use of methanol as an external carbon source. The control SBR, without methanol addition, achieved negligible denitrification. Two denitrification rates were observed in the experimental SBR, with methanol addition, an initial fast rate and a slower second rate. The denitrification rate during the first rate period increased with increasing methanol concentration, until a maximum denitrification rate of approximately 19 mg NOx-N/g MLVSS/day was attained. Following the depletion of the methanol, denitrification reactions probably continued by using the available natural carbon in the influent, resulting in a slower, second denitrification rate. Biological phosphorus uptake and release was significant only in the SBR with methanol addition. Methanol was probably not utilized as the carbon source for the enhanced biological phosphorus removal (EBPR) process. However, methanol addition was critical, since it depleted the available nitrates and thus allowed EBPR to take place.

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