Interrelationships Between Coating Uniformity and Efficiency in Pan Coating Processes.

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.

Optimization of Critical Quality Attributes in Tablet Film Coating and Design Space Determination Using Pilot-Scale Experimental Data.

In this study, the novel high-speed tablet film coating process in the continuous manufacturing was investigated. The influence of key process variables (inlet air flow rate, inlet air temperature, and suspension spray rate) were investigated using a Box-Behnken experimental design method. Statistical regression models were developed to predict the outlet air temperature and relative humidity, the coating efficiency, the tablet moisture content, and coating uniformity. The effects of the three key process variables were comprehensively investigated based on mathematical analysis, contour plots, and interaction plots. The results indicate that all the process responses are affected by changing the inlet air flow rate, temperature, and suspension spray rate. A design space (DS) in terms of failure probability was determined based on specifications for tablet moisture content (< 3.5%) and coating uniformity (tablet weight standard deviation < 4 mg for tablet weight of 200 mg) using Monte Carlo simulations. Independent experiments were carried out and successfully validated the robustness and accuracy of the determined DS for the investigated tablet film coating process. All the data were generated using an industrial pilot-scale novel high-speed tablet coating unit from a continuous manufacturing line. The work facilitates the quality by design implementation of continuous pharmaceutical manufacturing.

Novel Coating Uniformity Models for Tablet Pan Coaters.

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.

Application of Mathematical Models to Determine the Feasibility of Amorphous Drug Layering in Pan Coaters.

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.

Modeling the coating layer thickness in a pharmaceutical coating process.

Although mechanistic numerical simulations can offer great insights into a process, they are limited with respect to resolved process time. While statistical models provide long-term predictability, determining the underlying probability distributions is often challenging. In this work, detailed CFD-DEM simulations of a pharmaceutical Wurster coating process for microspheres are used to evaluate the input parameters for a novel Monte-Carlo simulation approach. The combined strengths of both modeling approaches make it possible to predict the coating mass and thickness distributions over the entire process time. It was observed that smaller beads receive a thicker coating layer since they pass the spray zone closer to the nozzle. Moreover, it was established that, in contrast to the airflow rate, the spray rate has a great impact on the inter-particle coating variability. A stochastic model was developed to investigate the relative contribution of coating layer variability and fill weight variability to the product non-uniformity in a capsule filling process of Multiple Unit Pellet Systems (MUPS).

Pharmaceutical Application of Tablet Film Coating.

Tablet film coating is a common but critical process providing various functionalities to tablets, thereby meeting diverse clinical needs and increasing the value of oral solid dosage forms. Tablet film coating is a technology-driven process and the evolution of coated dosage forms relies on advancements in coating technology, equipment, analytical techniques, and coating materials. Although multiple coating techniques are developed for solvent-based or solvent-free coating processes, each method has advantages and disadvantages that may require continuous technical refinement. In the film coating process, intra- and inter-batch coating uniformity of tablets is critical to ensure the quality of the final product, especially for active film coating containing active pharmaceutical ingredients in the coating layer. In addition to experimental evaluation, computational modeling is also actively pursued to predict the influence of operation parameters on the quality of the final product and optimize process variables of tablet film coating. The concerted efforts of experiments and computational modeling can save time and cost in optimizing the tablet coating process. This review provides a brief overview of tablet film coating technology and modeling approaches with a focus on recent advancements in pharmaceutical applications.

Passive Anti-Flooding Superhydrophobic Surfaces.

Superhydrophobic (SHPo) surfaces can provide high condensation heat transfer due to facilitated droplet removal. However, such high performance has been limited to low supersaturation conditions due to surface flooding. Here, we quantify flooding resistance defined as the rate of increase in the fraction of water-filled cavities with respect to the supersaturation level. Based on the quantitative understanding of surface flooding, we suggest effective anti-flooding strategies through tailoring the nanoscale coating heterogeneity and structure length scale. Experimental verification is conducted using CuO nanostructures having different length scales combined with hydrophobic coatings with different nanoscale heterogeneities. The proposed anti-flooding SHPo can provide a ∼130% enhanced average heat transfer coefficient with ∼14% larger supersaturation range for droplet jumping compared to a previous CuO SHPo. The proposed anti-flooding parameter and the scalable SHPo will help develop high-performance condensers for real-world applications operating in a wide range of supersaturation levels.

Effect of coating time on inter- and intra-tablet coating uniformity.

Film tablets are a common oral dosage from. For many of the functions film layers can have on pharmaceutical tablets, a high degree of coating uniformity is required. In studies on coating uniformity the coefficient of variation is commonly used as a marker. Previous studies regarding the trend were mostly extrapolations from simulations of short coating times. Based on these it was stated that the inter tablet coefficient of variation decreases proportionally to one over the square root of coating time and hence diverge asymptotically towards zero. Extrapolations of experimental data suggested however a decrease converging to a residual value. Based on these results it can be hypothesized that the coefficient of variation decreases proportionally to one over time towards a residual value. Regarding intra-tablet coating homogeneity, no data on time dependency has been published so far. In this study, three long time coating experiments were performed to test the described hypotheses. The inter-tablet uniformity was derived gravimetrically, while the intra-tablet data was derived using micro-computed tomography and confocal chromatic thickness determination. Towards the end of the coating experiments, a non-zero plateau of inter-tablet uniformity was reached. Furthermore, the data showed non-random deviations from the hypothesized one-over-square-root-of-time-model. The data for intra-tablet uniformity showed a non-linear decrease as well, but did not allow falsification of either hypothesis. It was additionally found that the cap-to-band ratio was below one at short coating times and increased to values above 1 during the process, which implies that existing declarations from literature might be limited to certain process durations.

The Development of a Uniform Alginate-Based Coating for Cantaloupe and Strawberries and the Characterization of Water Barrier Properties.

Water loss, gain or transfer results in a decline in the overall quality of food. The aim of this study was to form a uniform layer of sodium alginate-based edible coating (1.25% sodium alginate, 2% glycerol, 0.2% sunflower oil, 1% span 80, 0.2% tween 80, (w/w)) and investigate the effects on the water barrier characteristics of fresh-cut cantaloupe and strawberries. To this end, a uniform and continuous edible film formation was achieved (0.187 ± 0.076 mm and 0.235 ± 0.077 mm for cantaloupe and strawberries, respectively) with an additional immersion step into a calcium solution at the very beginning of the coating process. The coating application was effective in significantly reducing the water loss (%) of the cantaloupe pieces. However, no significant effect was observed in water vapor resistance results and weight change measurements in a climate chamber (80%→60% relative humidity (RH) at 10 °C). External packaging conditions (i.e., closed, perforated, and open) were not significantly effective on water activity (aw) values of cantaloupe, but were effective for strawberry values. In general, the coating application promoted the water loss of strawberry samples. Additionally, the water vapor transmission rate of stand-alone films was determined (2131 g·100 µm/(m2·d·bar) under constant environmental conditions (23 °C, 100%→50% RH) due to the ability to also evaluate the efficacy in ideal conditions.

Measurement of the Intertablet Coating Uniformity of a Pharmaceutical Pan Coating Process With Combined Terahertz and Optical Coherence Tomography In-Line Sensing.

We present in-line coating thickness measurements acquired simultaneously using 2 independent sensing modalities: terahertz pulsed imaging (TPI) and optical coherence tomography (OCT). Both techniques are sufficiently fast to resolve the coating thickness of individual pharmaceutical tablets in situ during the film coating operation, and both techniques are direct structural imaging techniques that do not require multivariate calibration. The TPI sensor is suitable to measure coatings greater than 50 µm and can penetrate through thick coatings even in the presence of pigments over a wide range of excipients. Due to the long wavelength, terahertz radiation is not affected by scattering from dust within the coater. In contrast, OCT can resolve coating layers as thin as 20 µm and is capable of measuring the intratablet coating uniformity and the intertablet coating thickness distribution within the coating pan. However, the OCT technique is less robust when it comes to the compatibility with excipients, dust, and potentially the maximum coating thickness that can be resolved. Using a custom-built laboratory scale coating unit, the coating thickness measurements were acquired independently by the TPI and OCT sensors throughout a film coating operation. Results of the in-line TPI and OCT measurements were compared against one another and validated with off-line TPI and weight gain measurements. Compared with other process analytical technology sensors, such as near-infrared and Raman spectroscopy, the TPI and OCT sensors can resolve the intertablet thickness distribution based on sampling a significant fraction of the tablet populations in the process. By combining 2 complementary sensing modalities, it was possible to seamlessly monitor the coating process over the range of film thickness from 20 µm to greater than 250 µm.