Pan Speed Research Articles

Effect of speed, loading and spray pattern on coating variability in a pan coater

A computational study using the discrete element method was performed to study the effect of pan speed, fill level and the design of the spray pattern on the coating variability of tablets coated in a rotating pan. The method simulates the movement of tablets in the pan and calculates the residence time of each tablet inside the spray zone, which is directly related to the amount of coating received by the tablet. The computational method was experimentally validated using a Laser Induced Breakdown Spectroscopy based analytical method. The simulations showed that the axial mixing was the most critical parameter affecting the coating variability. Although axial mixing was found to be better at higher pan speed, it did not affect the coating variability significantly. Lower variability was obtained when a 100% fill level was used as compared to 67% fill. Four spray patterns were used, two idealized (full surface spray and a symmetric band spray) and two realistic (5-ellipse and 5-circular spray guns). The full and band spray showed similar results while the ellipse and circular patterns were similar to each other (and much worse than the other two patterns) at all speeds and fill levels.

Experiments and numerical modeling to estimate the coating variability in a pan coater

The purpose of this work is to investigate the effect of the coating process parameters on coating performance and coating variability, and hence determine the optimal operating conditions. Coating of particles is done to mask the unpleasant taste or odor of the drug, to control the bioavailability of the API, and to increase shelf-life. The coating solution is sprayed in specific locations of the granular bed and coating uniformity is achieved by interparticle collisions and overall mixing behavior in the coater. Thus, good understanding of particle flow and granular mixing in a pan coater is vital to optimize the process parameters to reduce coating variability. Coating experiments are performed at previously determined optimal mixing conditions using Lactose nonpareils. The coating fluid (aqueous solution of Opadry II) is sprayed intermittently at different flow rates and concentration. Vernier Caliper is used to measure the change in diameter and the coating of the particles. Moreover, DEM based numerical modeling of spray coating is also performed for same operational parameter set and spray characteristic (center and the radius of the spray zone) used in the experiments. DEM simulation provides the residence time distribution of all the particles passing through the spray zone. The coating variability in the experiments is estimated at different pan and spray variables. The coating variability decreases with the increase inpan tilt, coating time and an optimum speed. The spray characteristics does not seem to have much effect on the variability although better coating is observed under better mixing conditions of high tilt and pan speed for the same spray parameters. The mass distribution of coated particles is quantified in the numerical model by the total number of particles passing through the spray zone and also by the frequency distribution of the residence time of the coated particles. It is observed that the simulations are in good agreement with the experiments for the effect of orientation (tilt) of the pan coater on coating variability. However simulations over predicted the effect of speed as compared to the experiments to reach the minimum coating variability. In the current study, the experimental setup did not reflect the typical bead coating setup used in the industry; rather depict a simplified setup to validate the numerical model.

Intra-tablet coating variability for several pharmaceutical tablet shapes

A combined discrete element method (DEM)–Monte Carlo simulation algorithm is used to investigate intra-tablet coating thickness variability for six pharmaceutical tablet shapes. The DEM simulations are used to collect tablet orientations when the tablets enter a specified spray zone. The Monte Carlo simulations are used to “coat” the tablets assuming a uniform spray and orientations chosen randomly from the distribution generated by the DEM simulations. The simulations demonstrate that for the non-spherical tablet shapes investigated here, the coating thickness variability, defined using a coefficient of variation, decreases with the square root of the number of coating trials, then approaches an asymptotic value. The greater the degree of a tablet's preferred orientation, the larger the asymptotic coefficient of variation. In addition, the number of trials required to reach this asymptote decreases for larger asymptotic values. These findings are consistent with theoretical analyses. For the range of parameters investigated, increasing the pan speed decreases the asymptotic coefficient of variation, but increasing the fill level had no consistent effect. The asymptotic coefficients of variation did not correlate with tablet sphericity, aspect ratio, or band-to-tablet area ratio, but the results suggest that a measure of a tablet's symmetry may provide better results. Modifying the angle of the coating spray so that a larger portion of the band is coated during each coating trial results in smaller asymptotic coefficients of variation than when the spray is oriented normal to the tablet bed surface. In addition, the relative order of the tablets with the smallest asymptotic coefficients of variation changes when the spray orientation is changed.

Modeling the motion and orientation of various pharmaceutical tablet shapes in a film coating pan using DEM

Film coating uniformity is an important quality attribute of pharmaceutical tablets. Large variability in coating thickness can limit process efficiency or cause significant variation in the amount or delivery rate of the active pharmaceutical ingredient to the patient. In this work, the discrete element method (DEM) is used to computationally model the motion and orientation of several novel pharmaceutical tablet shapes in a film coating pan in order to predict coating uniformity. The model predictions are first confirmed with experimental data obtained from an equivalent film coating pan using a machine vision system. The model is then applied to predict coating uniformity for various tablet shapes, pan speeds, and pan loadings. The relative effects of these parameters on both inter- and intra-tablet film coating uniformity are assessed. The DEM results show intra-tablet coating uniformity is strongly influenced by tablet shape, and the extent of this can be predicted by a measure of the tablet shape. The tablet shape is shown to have little effect on the mixing of tablets, and thus, the inter-tablet coating uniformity. The pan rotation speed and pan loading are shown to have a small effect on intra-tablet coating uniformity but a more significant impact on inter-tablet uniformity. These results demonstrate the usefulness of modeling in guiding drug product development decisions such as selection of tablet shape and process operating conditions.

Study of tablet-coating parameters for a pan coater through video imaging and Monte Carlo simulation

The movement of tablets in a pan coater and the exposure of different surfaces of tablets for deposition of coatings by spray-coating have been studied by video imaging and Monte Carlo simulation techniques. A representative variety of tablets of different shapes and sizes were used at different pan loads and at various pan speeds. A single “tracer” tablet was used to track the motion of tablets and coating variables such as circulation time, surface time, projected surface area and surface velocity of a tablet were determined from the video imaging experiments. The coating uniformity is described in terms of the coating variation from tablet to tablet CV(tt) and a new parameter CV(st) the coating variation on a single tablet. The effect of shape of tablets on coating uniformity was analyzed by introducing a “sphericity” of tablet ( φ s ) into the CV models. The methodology, new models and the analysis developed here incorporating the additional parameters will help users to optimize the coating process in pan-coating operations.

Modeling of Pan Coating Processes: Prediction of Tablet Content Uniformity and Determination of Critical Process Parameters

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.

Monitoring the Film Coating Unit Operation and Predicting Drug Dissolution Using Terahertz Pulsed Imaging

Understanding the coating unit operation is imperative to improve product quality and reduce output risks for coated solid dosage forms. Three batches of sustained-release tablets coated with the same process parameters (pan speed, spray rate, etc.) were subjected to terahertz pulsed imaging (TPI) analysis followed by dissolution testing. Mean dissolution times (MDT) from conventional dissolution testing were correlated with terahertz waveforms, which yielded a multivariate, partial least squares regression (PLS) model with an R2 of 0.92 for the calibration set and 0.91 for the validation set. This two-component, PLS model was built from batch I that was coated in the same environmental conditions (air temperature, humidity, etc.) to that of batch II but at different environmental conditions from batch III. The MDTs of batch II was predicted in a nondestructive manner with the developed PLS model and the accuracy of the predicted values were subsequently validated with conventional dissolution testing and found to be in good agreement. The terahertz PLS model was also shown to be sensitive to changes in the coating conditions, successfully identifying the larger coating variability in batch III. In this study, we demonstrated that TPI in conjunction with PLS analysis could be employed to assist with film coating process understanding and provide predictions on drug dissolution. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4866–4876, 2009

Studies in Optimization of Aqueous Film Coating Parameters

The purpose of this research was to study the aqueous-based film coating of tablets utilizing a laboratory-scale side-vented perforated pan-coating apparatus. The process parameters of potential importance with respect to the final film quality were evaluated by using trial and error method. Tablets were evaluated for coating uniformity (mg), coating process efficiency (%), surface roughness, and %LOD (loss on drying). Spray rate and inlet air temperature both affect the all characteristic of coated tablets. Rotating speed of pan mainly affect the coating uniformity of tablets. % Solid content affects the surface of coated tablets and also creates a problem in spray flow. The process parameters relevant to a side-vented perforated pan coating process can be identified and, consequently, optimized.

종자피복기의 피복통 회전속도가 피복종자의 물리적 특성에 미치는 영향

본 실험은 표준화된 피복종자를 생산하기 위하여 피복통의 회전속도를 20, 30, 40, 45, 55, 60 rpm으로 하여 소형 피복통으로 레드클로버와 톨페스큐 종자를 피복하였다. 고형물질로는 vermiculite를 사용하였고 접착제는 polyvinyl alcohol을 사용하였다. 피복 후 통에서 회수된 단립 피복종자 무게, 서로 달라붙어 덩어리진 피복종자 무게, 피복되지 않고 회수된 미 피복물질 무게, 충격에 의한 피복층 탈락성 및 피복종자의 백립중 등을 조사하여 피복종자의 물리적 특성을 평가하였으며, 이 자료를 근거로 피복효과를 종합적으로 표현하는 피복지수를 산출하였다. 레드클로버 종자는 통의 회전속도 45 rpm에서 회수된 단립 종자 무게가 제일 높았으며(p<0.01), 덩어리진 종자 수가 적고 피복물질의 탈락율이 적었으며, 피복종자의 백립중도 가장 무거웠다. 톨페스큐 종자는 피복통 회전속도 40 rpm에서 회수된 단립 종자 무게가 제일 높았으며(p<0.01), 덩어리진 종자 수가 적고 피복물질의 탈락율이 적었으며, 피복종자의 백립중도 가장 무거웠다. 통의 회전속도별 피복지수는 레드클로버는 45 rpm에서(p<0.01), 톨페스큐는 40 rpm에서 제일 높았다(p<0.01). 피복통의 회전속도는 피복종자의 물리적 성질에 크게 영향을 미치기 때문에 종자피복 전에 종자나 피복제에 따른 피복통 회전속도의 표준화가 필수적이라 하겠다. Using a small pilot coating pan, red clover and tall fescue seeds were coated under different rotating speed of pan(20, 30, 40, 45, 55, 60 rpm) for standardization of seed coating. Vermiculite was used as particulate matter and polyvinyl alcohol as adhesive for the coating of seeds. Coating index was calculated based on the percent singles out, percent agglomerates out, weight of particulate matter fine, percent friability, and average weight per 100 seeds to evaluate the physical characteristics of coated seeds. The coated seed of red clover under 45 rpm rotating speed of pan, was best in terms of percent singles out, percent agglomerates out, weight of fines, and average 100 seed weight. The coated seed of tall fescue under 40 rpm rotating speed of pan, showed highest percent singles out, lowest percent agglomerates out, lowest weight of fines, and heaviest average 100 seed weight. Excellent coating results were obtained with the pan speed of 45rpm for red clover and 40 rpm for tall fescue seeds. As rotatory speed of coating pan affected much to the physical characteristics of coated seeds, standardization of the speed is required before seed coating.

Inter-tablet coating variability: Residence times in a horizontal pan coater

This paper investigates inter-tablet coating variability, specifically, tablet residence times within the spray zone. Discrete element method computer simulations, experiments, and analytical investigations are performed to measure the residence time per pass, the circulation time, and appearance frequency of spherical shaped tablets for a range of pan speeds and tablet loads. In addition, the fractional residence time, defined as the ratio of time spent by a tablet in the spray zone to the total coating time, is measured. The average fractional residence time (averaged over all the tablets in the bed) is found to be equal to the ratio of the time-averaged number of tablets exposed to the spray to the total number of tablets in the pan, a result that is consistent with analyses. The average fractional residence time is observed to be independent of pan speed and total coating time. Furthermore, the fractional residence time is shown to be related to the residence time per pass and circulation time per pass. Appearance frequency is defined as the number of appearances a tablet makes in the spray zone per pan rotation. Simulations and analyses show that appearance frequency decreases with increasing pan speed. Circulation time per pass for a tablet is defined as the average time between successive appearances in the spray zone and residence time per pass is defined as the average time spent in the spray zone per pass. These various measures are all related, but from the standpoint of developing an analytical model for coating variability, fractional residence time is a more useful and intuitive parameter as it determines the fraction of total run time that a tablet spends in the spray. This paper concentrates on determining average fractional residence times and residence time per pass, while the inter-tablet variability is more closely related to the standard deviation of the fractional residence time.

Scale-up of a pan-coating process

The purpose of this work was to develop a practical scale-up model for a solvent-based pan-coating process. Practical scale-up rules to determine the key parameters (pan load, pan speed, spray rate, air flow) required to control the process are proposed. The proposed scale-up rules are based on a macroscopic evaluation of the coating process. Implementation of these rules does not require complex experimentation or prediction of model parameters. The proposed scale-up rules were tested by conducting coating scale-up and scale-down experiments on 24-inch and 52-inch Vector Hi-coaters. The data demonstrate that using these rules led to similar cumulative drug release profiles (f2 >> 50; and P Analysis of Variance [PANOVA] >> 0.05 for cumulative percentage of drug released after 12 hours [Cum12]) from tablets made at 24- and 52-inch scales. Membrane characteristics such as opacity and roughness were also similar across the 2 scales. The effects of the key process variables on coat weight uniformity and membrane characteristics were also studied. Pan speed was found to be the most significant factor related to coating uniformity. Spray droplet size was found to affect the membrane roughness significantly, whereas opacity was affected by the drying capacity.

Modeling weight variability in a pan coating process using Monte Carlo simulations

The primary objective of the current study was to investigate process variables affecting weight gain mass coating variability (CV(m) ) in pan coating devices using novel video-imaging techniques and Monte Carlo simulations. Experimental information such as the tablet location, circulation time distribution, velocity distribution, projected surface area, and spray dynamics was the main input to the simulations. The data on the dynamics of tablet movement were obtained using novel video-imaging methods. The effects of pan speed, pan loading, tablet size, coating time, spray flux distribution, and spray area and shape were investigated. CV(m) was found to be inversely proportional to the square root of coating time. The spray shape was not found to affect the CV(m) of the process significantly, but an increase in the spray area led to lower CV(m) s. Coating experiments were conducted to verify the predictions from the Monte Carlo simulations, and the trends predicted from the model were in good agreement. It was observed that the Monte Carlo simulations underpredicted CV(m) s in comparison to the experiments. The model developed can provide a basis for adjustments in process parameters required during scale-up operations and can be useful in predicting the process changes that are needed to achieve the same CV(m) when a variable is altered.

Prediction of tablet velocity in pan coaters for scale-up

The purpose of this study was to investigate the influence of scale-up on the tablet velocity and surface time of tablets (oblong and biconvex) in the spray zone of different perforated pan coaters. A Bohle Film Coater (BFC) 5 and 10 for the laboratory scale, a BFC 40 for the pilot scale and a BFC 200 for the production scale were used. The pan speeds were scaled-up using the same peripheral speeds. The tablet velocities for 5 peripheral speeds were determined using video imaging of blue tracer tablets. An increasing pan size resulted in a higher tablet velocity and lower surface time in the spray zone for same peripheral speeds. A mathematical model in the literature was proved to predict the tablet velocities in scale-up in the BFCs. The tablet velocities in the pilot or production scale can be predicted based on the measured tablet velocities in the laboratory scale. Furthermore, depending on the pan size, the increase in tablet velocity ( R V-value) can be predicted for the scale-up process using BFCs. The R V-values were validated for three pan sizes, different pan speeds and three different tablet types. The R V-value can be used as a correction factor to calculate the scaled-up spray rate based on the same spray rate per spray width ratios.

Influence of scale-up on the abrasion of tablets in a pan coater

The purpose of this study was to examine the influence of batch size during scale-up on the abrasion and edge splitting of flat faced lactose tablets. The weight loss of white tracer tablets in a batch of blue coated tablets was investigated in a laboratory scale pan coater and a pilot scale pan coater as a function of different pan speeds and mixing times. It was observed that increasing batch size resulted in a decreased weight loss due to less edge damaging. The higher number of tablet impacts at the pan wall in the laboratory scale compared to the pilot scale might be the reason for this phenomenon. The common assertion that an increase in batch size in scale-up leads to a higher abrasion or tablet damaging was not supported in the current study.

Simulation of particle movement in a pan coating device using discrete element modeling and its comparison with video-imaging experiments

A MATLAB™-based DEM (discrete element method) code was developed to study the particle motion in a pan coating device. The code was developed as a stand-alone program and provides simulation, visualization (GUI interface), and post-processing statistical analysis of particle movement. Results of DEM simulations are compared with those obtained from video-imaging experiments for 9 mm spherical polystyrene balls in a 58 cm diameter pan. The parameters compared are dynamic angle of repose and particle velocities in the x- (axial) and y- (parallel to cascading layer) directions within the spray zone in the cascading layer. The effects of pan loading and pan speed (6, 9, 12 rpm) on particle motion are compared and discussed. Good agreement was obtained between the DEM simulation and experimental results. The dynamic angle was found to increase with increasing pan speed and pan loading. The average cascading velocity was found to increase linearly with pan speed for both DEM and experiments. The velocity distributions both in the x- and y-direction were compared from simulation and experiments and found to be in good agreement. Velocity profiles along the entire top cascading layer of particles were also obtained using DEM. The particles in the cascading layer were found to reach their maximum velocity at positions close to the mid-point of the cascading surface. Comparison of simulated velocity profiles showed good agreement with published scaling laws for rotating drums, and a new correlation for scaling with respect to the pan loading is proposed.

Movement of different-shaped particles in a pan-coating device using novel video-imaging techniques

The purpose of this study was to investigate the effects of particle shape on the movement of particles in a pan-coating device using novel video-imaging techniques. An area scan CCD camera was installed inside a 24-in pan coater at the same location as that of a spray nozzle, and the movement of particles was tracked using machine vision. A white tracer particle was introduced inside a bed of black-coated particles. The effects of pan loading, pan speed, and particle shape on the movement of particles was studied. The response variables were circulation time, surface time, projected area of particle per pass, dynamic angle of repose, cascading velocity, and dispersion coefficient. Experiments were conducted at 3 different pan speeds, 6, 9, and 12 rpm, and 2 fill levels (ratio of bed depth to pan diameter), one eighth and one quarter, and data were collected over a 30-minute time period. The differences in circulation times of spheres and tablets, with similar volume equivalent diameter as that of the sphere, were found to be insignificant at the 95% confidence interval. The circulation time ranged from 2.8 to 10.8 seconds depending on the operating condition and increased with increasing pan load and decreasing pan speed. The distributions of circulation time, surface time, and projected surface area were found to be nonnormal. The dynamic angle of repose for tablets was higher than for spheres. Also, the bed surface for spheres was much flatter in comparison with tablets where the bed shape attained a "wave-like" form. The average velocity of tablets in the cascading layer was found to be significantly higher than spheres. A linear model (R(2) > 0.98) best described the variation of velocity as a function of pan speed for all of the operating conditions.

Use of experimental design for identifying the most important formulation and technological variables in pelletization by powder layering

The objective of this work was to identify, using a statistical experimental design, the critical process parameters that influence the pellets production by powder layering technique. A fractional factorial experimental design was used with five variables and two levels for screening the following parameters that can influence preparation of pellets: pan speed, powder application frequency, binder (polyvinylpyrrolidone) solution concentration, anti-sticking agent (talcum), wetting agent (sodium lauryl sulphate). Pellets containing indomethacin, chosen as the model drug, were prepared using a conventional coating pan. The results show that the most important variables in pellets production with the powder layering technique were: binder solution concentration, powder application frequency and pan speed. Anti-sticking agent (talcum) and wetting agent (sodium lauryl sulphate) had little influence on pellets proprieties obtained by the pan powder layering technique. Pellets with very good pharmaceutical quality (low proportion of sticked pellets, low friability and good flow properties) can be obtained in conventional coating pan via the powder layering technique with a good layering powder efficiency by using a relatively high pan speed and a high concentration of binder solution.

Process and Formulation Variables Affecting the Performance of a Rupturable Capsule‐Based Drug Delivery System with Pulsatile Drug Release

The objective of this study was to optimize several process and formulation parameters, which influence the performance of a rupturable, pulsatile drug delivery system. The system consisted of a drug‐containing hard gelatin capsule, a swelling layer of croscarmellose (Ac‐Di‐Sol®) and a binder, and an outer ethylcellulose coating. Polyvinyl pyrrolidone (Kollidon 90F) was superior to HPMC and HPC as a binder for the swelling layer with regard to binding (adherence to capsule) and disintegration properties of the swelling layer. The capsule‐to‐capsule uniformity in the amount of swelling layer and outer ethylcellulose coating, which significantly affected the lag time prior to rupture of the capsule, was optimized by decreasing the batch size, and by increasing the rotational pan speed and the distance between the spray nozzle and the product bed. The type of baffles used in the coating pan also affected the layering uniformity. Fully‐filled hard gelatin capsules had a shorter lag time with a higher reproducibility compared to only half‐filled capsules, because the swelling pressure was directed primarily to the outer ethylcellulose coating and not to the inner capsule core. Stability studies revealed that the lag time of the capsules was stable over a 240‐day period when the moisture content was kept unchanged.

Coating uniformity and coating efficiency in a Bohle Lab-Coaterusing oval tablets

The aim of this study was the examination of the influence of tablet size (two different sized oval tablets), batch size, pan speed and inclination of the rotation axis on the coating uniformity and efficiency in a Bohle Lab-Coater BLC 5. The coating uniformity was appraised using the mass variance, the dissolved amount of acetaminophen after 2 h in hydrochloric acid pH 1.0 at a polymer loading of 3 mg/cm 2 and the minimum amount of polymer for an enteric coating. The mass variance of the final tablets decreased with increasing pan speed. There was a linear and quadratic effect in the case of small oval tablets and a linear effect for the large tablets. The minimum amount of polymer required for gastric resistance depends on the pan speed for both tablet sizes. The dissolved amount of acetaminophen after 2 h in simulated gastric fluid was influenced linearly by the batch size for both kind of tablets. In the case of the large oval tablets it was also influenced by the pan speed, the batch size and the inclination of the rotation axis. The dissolved amount of acetaminophen increased with increasing pan speed and batch size. A relation between the coating process efficiency and the investigated influence variables could not be established.

Identification of critical process variables for coating actives onto tablets via statistically designed experiments

The objective of this work was to identify, using a statistical experimental design, the critical processing variables that affect content uniformity and loading of active agent coated on tablets in a 24″ Accela-Cota. United States Pharmacopeia (USP) specifies that the % relative standard deviation (RSD) of drug content within a batch should be less than 6%. A Plackett–Burman experimental design was used to identify the process variables that influence the content uniformity and loading efficiency of the drug in the aqueous-based film coat of the tablets. The process variables investigated were inlet airflow, pan speed, inlet air temperature, coating time, atomization pressure, and fan pressure. Atomization pressure was identified as a major variable with respect to content uniformity ( P<0.01). Pan speed and coating duration were also identified as variables significantly affecting content uniformity ( P<0.05). Fan pressure was identified as a critical variable affecting recovery ( P≪0.01). Temperature also significantly affected recovery ( P<0.05). A good correlation was obtained between observed and predicted values for content uniformity ( r 2=0.85) and recovery ( r 2=0.95). It was possible to achieve % RSD less than 6% while maintaining the recovery at 80% or higher.