DE60021587T2 - SYSTEM FOR CONTROLLING EVAPORATIVE DRYING PROCESSES USING ENVIRONMENTAL EQUIVALENCE - Google Patents

Abstract

Methods and systems for controlling evaporative drying processes using environmental equivalency control process parameters to provide a specified product quality. In an environmental equivalency-based control system, measured values are received by environmental equivalency calculation hardware or software. An environmental equivalency value is calculated based on the measured parameters. One or more of the process parameters may then be varied to maintain the environmental equivalency value for the process within a predetermined range of environmental equivalency values.

Description

technical area

The The present invention relates to an evaporation drying system with a computer / control unit.

Background of the field

Evaporation drying method, for example, tablet film coating, spray drying and fluid bed processing, use evaporation drying to achieve a desired quality of finished To achieve product. For example, in tablet film coating Tablets in a coating pan of a tablet coater arranged. The coating pan is a perforated or semiperforated Cylinder, similar in appearance the drum of a conventional tumble dryer. While the coating pan rotates becomes a coating material, for example a solution or a suspension sprayed on the tablets. To the coating material drying the tablets, heated gas, such as air, over one Gas inlet in the chamber pumped or sucked. The gas leaves liquid from the coating material evaporates and flows over one Gas outlet off.

Some parameters associated with tablet film coating are:
Temperature of the drying gas;
Dew point;
Flow rate of the drying gas;
spray; and
Percentage of solids in the solution / suspension.

Around using conventional methods To achieve a proper coating of tablets must be optimal Values for each of these parameters can be determined empirically. In addition, subsequent processes must careful be controlled to ensure that the optimal parameter values be maintained.

Around optimal values for To determine the parameters of the tablet film coating, many attempts must be made carried out become. For example, a process engineer may start to use tablets in a tablet coater using initial values for the coat the above listed parameters. The quality of the coating The tablets can be analyzed to make the necessary adjustments to determine the parameter. This process is repeated until optimal Values for the parameters are determined. The optimal parameter values will be then in a control device, such as a programmable Logic control, programmed to the subsequent coating of tablets to control.

The empirical method for the determination of optimal parameter values is for several reasons undesirable. If multiple attempts are needed to get optimal parameter values To determine, many hours of operation of the tablet coater are necessary. Consequently, it may be for A drug manufacturing company may be required to stop production to slow down or to maintain a given level of production, to buy several tablet coaters. The empirical determination of the optimal process parameters required increased Time and / or equipment costs elevated the price for the development of evaporation drying processes, for example Tablet film coating.

One other with a conventional one Development of evaporation drying processes related Problem is that the conventional Development of evaporation drying processes product-specific is. In other words, experimental tests have to be done for every new product for optimal process parameters to investigate. This testing increases undesirable the with conventional Evaporation drying processes related work and expense.

One another reason that the conventional empirical Method for determining optimal process parameter values is undesirable, is that results are not scalable. For example, it could be that for a small tablet coaters did not determine parameter values for a larger tablet coater valid are and vice versa. Consequently, could it be that new Parameter values must be determined when the scale of a Process changes. Furthermore could it is that model parameters, the for a process environment are valid, not transferable to another process environment are. For example, could it be that parameter values for one Tablet film coating process, in a geographical area with a high relative humidity is operated, not to another geographical area with a low relative humidity are transferable. Consequently, empirical Attempts are being made in the new geographical area um for that new area to determine optimal parameter values. This one with one usual Tablet film coating process control related lack in terms of scalability and portability has an elevated Labor and expense result.

Another problem associated with tablet film coating is the time required to begin coating tablets NEN. For example, in a conventional tablet coating, minutes or even hours might be required to achieve operating parameter values. This increased start-up time reduces production for a given tablet coater.

One another problem associated with conventional tablet film coating is that, if while In a tablet coating operation, one or more process parameters change this change negative on the quality of the finished product. For example, if the Moisture or the temperature of the inlet air changes during a tablet coating operation, it could be that others Parameters during require an adaptation of the establishment, about the changes to compensate. Such compensation could be a continuous monitoring and manual adjustment by an operator throughout the tablet coating process require. Thus, you can conventional methods For the production of pharmaceutical products very labor intensive be.

"A Thermodynamic Model for Aqueous Film Coating ", Pharmaceutical Technology, April 1987, by Glenn C. Ebey, Thomas Engineering, describes what is known as Environmental Equivalence (EE), dimensionless size, the can be used to specify relationships between process parameters with aqueous film coating related, to model. In the publication an example is given in which environmental equivalency is used to a new intake air temperature for one Tablet coater to determine a desired environmental equivalency value to generate when the intake air humidity changes. The new intake air temperature is determined as follows. First, the example states that "a good coating quality at a Intake air temperature of 149 ° F, one Air flow rate of 2000 effective cubic feet per Minute, a moisture ratio of 25 grains per pound of mass and a spray rate of 400 grams per minute using a solution with 10% solids. "Based on these parameters an EE value of 2.990 is calculated. The humidity of the process environment changes to 125 grains per pound of mass. The inlet air temperature required is to maintain the same EE value is then calculated. In the example, an inlet air temperature of 160 ° F results to the same EE value.

While the publication a method for modeling film coating processes under Use of environmental equivalency in theory, shows the example given above just how to change a variable associated with a film coating process, a sudden change to compensate for another variable while keeping the remaining parameters constant become. In a real tablet coating system can become while a tablet coating operation change several parameters and / or need an adjustment. Such multi-variable changes and adjustments are not addressed in the publication.

A other inadequacy the publication is that no Control system for continuously adapting process parameters is disclosed for maintaining EE values. In the above example will be at a change The moisture of 25 to 125 grains per pound of mass is a new one Intake air temperature calculated so that the EE value is 2.9. Such calculations may be for a sudden change the moisture useful be, for example, one that occurs when a process of one geographical location is relocated to another and to the new one Place the humidity remains constant. However, in real systems, process parameters sinusoidal vary around setpoints around, as by time constants of respective tax systems for process parameters is predetermined. Thus, it is desirable in a real system process parameters continuously measure and use the measured values to a desired Maintain EE value.

A further inadequacy the publication is, that you no preferred ranges of EE values for tablet film coating discussed. After all deals the publication not with an application of environmental equivalency control to others Evaporation drying processes as the aqueous tablet film coating, for example spray drying, Fluid bed processing or other evaporation drying processes.

in view of These difficulties exist in the pharmaceutical industry and in other industries that use evaporative drying an urgent need for improved methods and systems for Control of processes using environmental equivalency.

Summary the invention

According to the present invention as defined in claim 1, control systems based on environmental equivalency are applied to evaporation drying processes such as tablet film coating, spray drying, textile manufacturing, food processing, deposition of materials on substrates in semiconductor manufacturing, painting, chemical and petrochemical isolation or purification, removal of contamina tions and fluid bed processing. Parameters associated with an evaporation drying process are continuously monitored and fed to an environmental equivalency calculator / controller. As used herein, continuous monitoring of process parameters refers to sampling process parameters at fixed or variable time intervals during an evaporative drying process. The environment equivalency calculator / controller calculates an environmental equivalency value for the process and compares the value to a preferred range of values. If the calculated environmental equivalency value is not within the desired range of values, the environment equivalency calculator / controller calculates a value for one or more parameters associated with the evaporative drying process and applies the new parameter value to the process. In this way, the environmental equivalency based control systems according to the present invention are able to maintain the environmental equivalency value for a process within a desired range of values. Consequently, a constant product quality can be achieved even if parameters change during the operation being performed. In addition, since the control systems that use environmental equivalency are product-independent, the overall efficiency of a process is increased.

environmental equivalency can also during the process transfer of evaporation drying processes, for example Tablet coating, fluid bed processing, spray drying, textile manufacturing, Food processing, deposition of materials on substrates in semiconductor manufacturing, painting, chemical and petrochemical Isolation or cleaning and removal of contamination. As As used herein, the term "process transfer" refers to the process of transfer the production of a special product from a manufacturing system to another, e.g. Film coatings of the same drug product on two different models / sizes of tablet coaters. The EE value is a dimensionless value that indicates the rate of the drying process indicates. The EE value may be aqueous or solvent-based Processing for the existing operation are applied. In short, he is used to describe the nature of the environment of the process. The nature of Environment of a process refers to the relative rates, with which heat and mass into the system and out of the system become. The EE value becomes an explicit mathematical expression which is a function of process-dependent variables. The expression that to calculate environmental equivalency is derived from the first principles using of mass and energy balances around the drying system.

Applied on the pharmaceutical industry, environmental equivalency is a very valuable one Tool during process transfer. Evaluation, monitoring and control of the environmental equivalency factor may be used be to the quality of the drug product being processed directly to influence. In the development of a particular product has For example, the tablet coating process has an associated EE value. For the Case, that the Tablet coating process of one Pilot should be raised to a production level, the EE value of the larger scaled plant customized to achieve the same product quality. Equally it is possible This method also on the scaling down for the Apply production of smaller batches. Process parameters can be varied to maintain a constant EE value. A determination of this process parameters in fact creates the scaled "recipe" of the product on the special part of the product used process plant.

The for the calculation of the environmental equivalency value The formula used is derived from mass and energy balances the process streams with application of the first law of thermodynamics on the drying system starting from a "black box" approach. The special model presented here is tailored to aqueous drying processes, for example, aqueous tablet film coating. The formula is as follows:

The variables used are defined as follows:
A _H = heat transfer surface
A _M = mass transfer area
M = molecular weight of water [1b _m / 1b - mol]
p _W = water vapor partial pressure at mass transfer conditions [1b _f / ft ² ]
p _f = water vapor partial pressure in free air flow [1b _f / ft ² ]
R = universal gas constant [[1b _f - ft / 1b _m - mol - ° R]
T _W = temperature at the mass transfer conditions [° R]
T _f = free air flow temperature [° R] h _ig = enthalpy change of water [BTU / 1b _m ]
p = density of air flow [1b _m / ft ³ ]
C _p = specific heat capacity of air [BTU / 1b _m - ° F]
T _B = temperature of the heat transfer surface [° R]

The technical definition of EE is the ratio of the area of heat transfer A _H to the area mass transfer A _M. Low EE values near 1 indicate wet processes. Higher values indicate drier conditions.

Even though the parameters in the equation are an elimination of water from one Show product in air, the present invention is not on limited elimination of water from a product in air. For example can according to the present Invention environmental equivalency also on solvent-based Drying processes and drying processes, in which a Drying in gases other than air. For example, for Tablet film coating, spray drying, Fluid bed processing or any other evaporation drying processes any noble gas may be used to dry the product. Furthermore can organic solvent used to coat a product. If the solvent and / or the drying gas must be modified, the variables in the equation according to the physical and chemical properties of the used solvent and / or drying gas changed become. Furthermore can work for other solvents change the preferred range of environmental equivalence values as water.

Application on tablet film coating

Aqueous film coating is a for the manufacture of the tablet dosing type critical core process. current Coating process transfer processes are often ineffective and involves many expensive experimental trials to achieve the desired end product quality. An implementation of the EE model can eliminate these inefficiencies and ensure the practical development of recipes for larger-scale production.

at the application of an environmental equivalency based control on the tablet coating process there are both constant as well as variable factors along with assumptions. The model is set advance that the Process adiabatic and thermodynamically ideal. Adiabatic processes are those at those of heat transfer to the environment is zero. In this case, the entire heat, the led into the system will, over the Process streams out guided, and not the environment of the coater (air, walls, etc.) around the coater around). The model is described as thermodynamically ideal, as it is the basic fundamental equations for quantifying mass and heat transfer used without consideration non-linear properties of the chemicals involved. These requirements apply to the areas of the operating parameters for evaporation drying processes to.

factors and conditions that are not in the evaluation of environmental equivalency for tablet film coating can be included are pan speed, nozzle shape, Location of the temperature sensors, load size and tablet geometry. These factors have a negligible effect on heat and heat Mass transfer and therefore do not affect the drying process.

The principal Variables of an aqueous tablet coating, the for a calculation of environmental equivalence values are critical, are inlet gas temperature, Gas flow rate, Moisture, Percentage of solids in the coating solution and Spray rate. amendments these variables cause changes the environmental equivalent value. An increase in the Temperature of the inlet gas, the flow rate the inlet gas and the percentage solids cause an increase in the Environmental equivalency value, increase the drying rate. An increase the humidity of the inlet gas and the spray rate cause a lowering of the environmental equivalent value, reduce the Drying rate. The present invention includes methods and systems for continuously measuring and adjusting process parameter values by one desired Range of environmental equivalence values maintain.

Accordingly, a Object of the invention, a system for controlling evaporation drying processes using environmental equivalency provide.

These Task is solved with the features of claim 1.

Short description of drawings

A Description of the invention will now be made with reference to the attached Drawings:

1 Fig. 10 is a block diagram of a tablet film coating system having an EE calculator / control unit according to an embodiment of the present invention;

2 Fig. 10 is a flowchart showing an EE calculator / control unit according to an embodiment of the present invention;

3 Fig. 10 is a flow chart showing a control parameter calculation routine according to an embodiment of the present invention; and

4 Fig. 10 is a flow chart showing a fatal error detection routine according to an embodiment of the present invention.

Detailed description the invention

1 Fig. 10 is a block diagram showing a tablet film coating system having an EE calculator / control unit according to an embodiment of the present invention. In 1 carries a tablet coater 100 a film coating on tablets. The tablet coater 100 may comprise any tablet coater suitable for applying a film layer to pharmaceutical tablets. Exemplary tablet coaters suitable for use with the present invention include HI-COATER Model No. 10 HCF-130, available from Vector Corporation, DRIACOATER, Model No. 500, available from Driam GMBH & Company, GLATTPAN, available from Glatt Air Technologies and ACCELA-COTA, available from Thomas Engineering Inc. As mentioned above, the tablet coater 100 a pan for holding and spinning tablets, one or more spray nozzles for spraying a film layer on the tablets, a pump for discharging the process liquid to the spray nozzles, a gas inlet for flowing a drying gas into the pan, and a gas outlet for Ejecting gas from the pan.

A monitoring and control system 102 includes process parameter sensors and controls that measure and control process parameters. For example, the monitoring and control system 102 temperature sensors, for example, thermocouple pairs or resistance temperature difference (RTD) sensors for measuring the temperature of the inlet gas, moisture sensors for measuring humidity, and gas flow meters for measuring flow rates of inlet and outlet gases. To control the process parameters, the monitoring control 102 a controller, such as a programmable logic controller (PLC) or other hardware combination, software combination or combination of hardware and software that receives the measured process parameter values and outputs control signals to maintain optimal process parameter values. A human machine interface (HMI) 104 allows the user to monitor and manually control process parameters. For example, the man-machine interface 104 a computer interfacing with the programmable logic controller and the sensors. A representative computer for use in the man-machine interface 104 is a T-60 available from Allen-Bradley Corporation.

An EE computer / control unit 106 receives measured process parameter values from the sensors, calculates an environmental equivalency value based on the measured process parameter values, and outputs to the programmable logic controller a control signal based on a desired EE value. The EE computer / control unit may be implemented as hardware, software or as a combination of hardware and software. For example, in a preferred embodiment of the invention, the EE computer / control unit 106 with the programmable logic control of the monitoring control 102 be integrated. However, in the embodiment shown, the EE computer / control unit is 106 separately for monitoring control 102 , In such an embodiment, the EE computer / control unit 106 a program running on a laptop computer that receives measured process parameters via the serial port of the computer and outputs control signals. A suitable laptop computer would be a THINKPAD ^®, available from IBM Corporation.

2 FIG. 10 is a flow chart showing exemplary steps taken by an EE computer / control unit 106 according to an embodiment of the present invention can be performed. In step ST1, the EE computer / control unit receives 106 user input process parameter initial values. The process parameter initial values input by the operator may be via the HMI interface 104 be received. Process parameters that may initially be specified include inlet temperature, dew point, drying gas flow rate, spray rate, and percent solids of the solution or dispersion. In step ST2, the EE calculator / control unit starts 106 the tablet coating process using the process parameter initial values. Step ST1 and ST2 are applicable to a direct control embodiment in which the EE computer / control unit 106 with the monitoring control 102 is integrated. In an embodiment in which the EE computer / control unit is not in the supervisory control 102 can be omitted, the steps ST1 and ST2 can be omitted, as these functions outside the EE computer / control unit 106 would be performed.

In step ST3, the EE computer / control unit receives 106 measured process parameter values. The measured process parameters may include temperature of the inlet gas, dew point, flow rate of the drying gas, spray rate, and percent solids of the solution or dispersion. In a preferred embodiment of the invention, the temperature of the inlet gas, the dew point and the flow rate of the gas are continuously measured. The percent solids of the solution or dispersion can also be measured. However, on the basis of the film layer mixture, this value may be pre-determined be known. In step ST4, the EE calculator / control unit calculates 106 based on the measured parameter values, an environmental equivalency value. In step ST5 and ST6, the EE calculator / control unit determines 106 whether the calculated EE value is within a predetermined range. In a preferred embodiment for aqueous film coating, the EE setpoint is preferably about 4.41. An EE set point of approximately 4.41 results in tablets that meet the Military Standard 105E for an acceptable quality limit (AQL) "(Military Standard 105E for an acceptable quality limit) of 0.65 for aqueous film coating. A range of EE factors that give tablets within a 95% confidence interval for an AQL value of 0.65 is from about 3.74 to not more than about 5.20. Accordingly, for tablet film coating, the preferred range of EE values may advance into the EE computer / controller 106 be programmed.

physical Construction elements of process plants, For example, tablet film coater may deviate from preferred ranges EE values. For example, the location of a measuring element, the pan construction and other parameters deviations from the preferred one Create EE area. Deviations for individual plants can be determined experimentally be by the quality of the finished product is analyzed. However, considered the confidence interval described above the deviations in terms on different coating pans with the same functional principles, but different capacities, e.g. 1 kg to 400 kg.

If in step ST6 the EE computer / control unit 106 determines that the environmental equivalency value is not within the desired range, calculates the EE calculator / control unit 106 new values for one or more process parameters so that the EE value will be within the desired range (step ST7). For example, the EE computer / control unit 106 calculate new values for the temperature of the inlet gas, the dew point, the flow rate of the drying gas and / or the spray rate. In a preferred embodiment, the EE calculator / control unit calculates 106 a new value for the spray rate. A preferred method of calculating a new value for the parameter (s) to be controlled to achieve a desired EE value is discussed in more detail below. In step ST8, the EE computer / control unit uses 106 the newly calculated values on the process.

After changing the process parameter (s), the EE calculator / control unit returns 106 to step ST3 and receives new measured process parameter values. The new process parameter values are used to calculate a new environmental equivalency value. The new environmental equivalence score is checked to see if it is within the desired range. Process parameter values may be changed again if the environmental equivalency value is not within the desired range. The system preferably continuously repeats steps ST3 through ST8 to achieve and maintain the desired environmental equivalency value. As the EE value is continually updated, product quality is maintained even if one or more measured parameter values change.

Control parameter calculation routine

3 FIG. 12 shows a control parameter calculation routine for calculating a control parameter value that yields a calculated environmental equivalent value that is within the desired range of environmental equivalency values. As used herein, the term "control parameter" refers to a process parameter used by the environmental equivalency calculator / control unit 106 is adjusted to control an evaporation drying process.

In the 3 The steps shown correspond to step ST7 of FIG 2 , For example, as noted above, the preferred control parameter for the tablet film coating is the spray rate. Additional or alternative control parameters that may be used include temperature of the inlet gas, inlet gas flow rate, and percent solids of the solution or dispersion.

In Step ST1 calculates the control parameter calculation routine environmental equivalency using a control parameter value. The control parameter initial value can be any value, for example 1. The other parameters used to calculate the environmental equivalency are measured from the tablet coating process. In step ST2 and ST3, the control parameter calculation routine compares the calculated environmental equivalent value with the upper range limit of the desired range of environmental equivalence values. If the calculated environmental equivalent value is above the upper limit, the control parameter calculation routine changes the control parameter value and recalculates an environmental equivalency (ST4) using the new control parameter value. If, for example the control parameter the spray rate is, the control parameter calculation routine can increase the spray rate since Increase the spray rate the calculated environmental equivalent value decreased. For other parameters, such as gas flow rate, which can change directly to environmental equivalency the control parameter calculation routine lowers the control parameter initial value.

The Steps ST1 to ST4 are repeated until the calculated environmental equivalent value no longer above the upper limit. In step ST5 stores the control parameter calculation routine the control parameter value representing the calculated environmental equivalency value which is less than or equal to the upper limit. In step ST6 changes the control parameter calculation routine the control parameter value and recalculates the environmental equivalency. In step ST7 and ST8, the control parameter calculation routine compares the calculated environmental equivalent value with the lower limit of the desired Range. If the calculated environmental equivalent value is below the lower one Range limit, the control parameter value is changed and the environmental equivalency is changed using the Control parameter value recalculated (ST9).

Steps ST7 to ST9 are preferably repeated until the calculated EE value is no longer below the lower range limit. In step ST10, the control parameter calculation routine stores the control parameter value that gives the environmental equivalent value that is no longer below the lower limit. In step ST11, the control parameter calculation routine calculates the control parameter end value by averaging the stored control parameter values. After the control parameter end value has been calculated, control returns to step ST8 of FIG 2 back in which the calculated control parameter value is applied to the film coating process.

In the 3 The control parameter calculation routine shown generates a control parameter value that is designed to give an environmental equivalency value in or near the center of the desired environmental equivalency range in the process to be controlled. In a direct control embodiment, the control parameter value calculated by the control parameter calculation routine may be applied directly to the process to be controlled. In an indirect control embodiment, the control parameter value may be sent to the supervisory controller 102 which then uses the calculated control parameter value to adjust the control parameter in the process.

Application of EE control on spray drying

The The present invention is not a use of environmental equivalency limited to controlling a tablet film coating in a drug production process. The Use of environmental equivalency for controlling any evaporation drying process, both in a drug production process as well as in other production processes should be included within the scope of the invention. For example, includes in an alternative embodiment The present invention Methods and systems for controlling spray drying using environmental equivalency. Spray drying is a process a fluid pumpable medium in a dry powder or particle form transforms. This drying is done by atomizing the fluid into a drying chamber reaches where liquid droplets pass through passed a gas stream become. The purpose is a spray from droplets with high surface area / mass ratio too produce. The droplets have ideally same size. After this the droplets sprayed into the drying chamber Preferably, the water or other liquid becomes fast and evenly evaporated. Spray drying can a process in the drug manufacturing industry as well as one process in another Industries, such as food and confectionery processing, chemical or petrochemical processing, environmental protection, for example wet cleaning, Spray painting, semiconductor manufacturing, textile manufacturing or any other industry using an evaporation drying process. In the spray drying can the feed be a solution a suspension or a paste. The dried product can be powdery, granulated or agglomerated. The properties of the dried Hang products from the feed, the dryer design and the process conditions from. Spray drying gives a powder with a specific particle size and a specific moisture content. Delivered in a continuous operation the spray dryer a very controlled powder quality with a relatively simple Control.

• • Zerstäuben der Beschickung;
• • Sprühgaskontakt;
• • Trocknung; und
• • Trennung des getrockneten Produkts von dem Trocknungsgas.

In its simplest form, spray drying consists of four process steps:

• • atomizing the feed;
• • spray gas contact;
• • drying; and
• Separation of the dried product from the drying gas.

• • eine Einzelfluid- oder -druckdüse;
• • eine Doppelfluiddüse; oder
• • einen Rotationszerstäuber, auch als Drehscheibe oder Rad bekannt.

Atomizing is generally carried out by one of the three basic devices:

• • a single fluid or pressure nozzle;
• • a double fluid nozzle; or
• • a rotary atomizer, also known as a turntable or wheel.

The Einzelfluiddüse allows greater versatility with regard to an arrangement with the spray chamber, the spray angle or the spray direction changed become.

Since the particle size depends in part on the feed rate, nozzles have limits in terms of product properties and operating rates. Once the nozzle is in place The rates can only be changed by pressure. Changing the opening requires removal of the nozzle. In large volume operating processes, many nozzles are within the chamber and are arranged to maintain constant vaporization conditions around each nozzle. For more viscous and abrasive feeds, dual fluid nozzles are used, with one gas, such as air, being the second medium to move the feedstock and effectively atomize it. Air can be mixed inside the nozzle or outside the nozzle. Under conditions where a single fluid nozzle would not allow small particle sizes, the dual fluid nozzle can provide the necessary additional atomization. However, this creates a broader particle size range. Fluid feedstocks may also be dispersed or atomized by centrifugal force on a rotary or centrifugal disc. Liquid feed is accelerated to more than 300 feet / second to produce very fine droplets. The particle size is controlled mainly by the disk speed. In centrifugal systems, the liquid feed material is applied in the center of the disk, moves as a thin layer over the surface and is spun off the edge in the form of small droplets. Wings or a disc with a rough surface can minimize slippage of the fluid as it is thrown to the outside of the disc.

any Number of dryers can be used to make a pharmaceutical or spray-dry other product. Exemplary dryers for use with embodiments of the present invention include cylindric Flat bottom dryers and cone bottom dryers, such as the "HT" and the "Virtis", Model No. SP-04, both available from Niro Incorporated. The drying gas inside the chamber of a Dryer holds a flow pattern upright, creating a deposit of partially dried product is prevented on the wall of the chamber or the atomizer. A Movement of the drying gas may be a flow in the same direction (flowing in the same direction), in opposite direction (countercurrent) or be a mixed flow. Direction of movement of the drying gas and temperature of the inlet gas affect the Type of final product. For a constant rate of drying is a maintenance of surface wetting of the particle important. When the temperature of the drying gas is too is high, a dried layer can form on the surface, which reduces the evaporation. Drying takes place in two phases and To control these phases is a control of the temperature of the Drying gas essential. The first phase is the step with constant Rate at which moisture quickly evaporates from the surface and capillary action draws moisture from within the particle. In the second period or period the rate decreases the diffusion of water to the surface the drying rate. With decreasing moisture content is a single stage dryer for the most part the residence time in the dryer responsible. In general, that is Residence time of the drying gas and that of the particle in one single-stage co-current dryer approximately equal. Because the moisture level always goes towards the end of the process still decreasing, the Outlet temperature sufficient be high to continue the drying process. An add a Fluid bed after the dryer can complete the drying process to ensure.

The Final phase of spray drying is removing the dried product from the drying gas an economical and pollution-free way. Generally, the hangs Economics of the recyclability of the drying gas Thus, the removal of fines from the drying gas very important. Dependent From the dryer construction, the product can be attached to the base, such as for example, in a flat-bottomed dryer, and be separated can Fines can be collected in any type of collection facility. Alternatively you can the product and the drying gas are led together to a plant, the one for that is designed to separate particles from the drying gas. Heavier product is eliminated by gravity, but fines require additional Disposal facilities. The fines can be removed with the help of cyclones, Bag filters, electrostatic precipitators or scrubbers be eliminated. Fines are bagged or recycled to an agglomeration process and the drying gas is returned to the system.

In accordance with conventional spray drying processes, maintaining optimum process parameters for spray drying is similar to the conventional methods described above for maintaining optimal parameters for tablet film coating. In other words, optimal process parameters are determined empirically and then applied to produce a production quality product. If one or more parameters change during processing of a given batch of material, the quality of the final product is reduced. In addition, the same problems of lack of scalability and adaptability to process changes that apply to tablet film coating also apply to spray drying. For example, spray dryers are generally designed to maintain constant flow rates of the drying gas receive. The temperature of the inlet gas is preferably adjusted so that the solution can be sprayed into the dryer with as high a feed rate as possible. Once the temperature of the inlet gas and gas flow rate have been adjusted, then the feed rate is adjusted according to the desired product quality. If the humidity, temperature or flow rate of the drying gas changes, it may be that the feed rate needs adjustment.

Environmental equivalency can be used to maintain product quality when one or more parameters change during a process. In the 2 and 3 ge showed process steps can be applied to spray drying. First, for a spray-drying process, a desired range of equivalence values can be determined. The desired range can be determined empirically by examining the product quality and calculating a range of environmental equivalency values that give the desired product properties. Since spray drying processes are typically drier than tablet film coating processes, the preferred range of environmental equivalents for spray drying may be higher than the preferred range for tablet film coating noted above.

After the desired range of environmental equivalency values has been determined, the range can be used to provide a similar control system to that in FIG 1 realized control system to control one or more parameters, for example, an optimal feed rate. The process steps of 2 can be used to control a film coating process. In the 3 The process steps shown may be used to calculate a feed rate that gives an environmental equivalency that is within the desired range of values.

Control of fluid bed processing using environmental equivalency

According to one another embodiment may The present invention relates to methods and systems for controlling Fluid bed processing using environmental equivalency include. As with the other embodiments set forth herein The invention relates to the methods and systems for controlling Fluid bed processing not limited to the pharmaceutical industry, but other industries, such as food and beverage and confectionery processing, chemical or petrochemical processes, environmental protection, for example Wet cleaning, spray painting, Semiconductor manufacturing, textile manufacturing or any other industry, uses the evaporation drying processes. Fluid bed processing is used to granulate, coat or disperse particles to agglomerate. In fluid bed processing there is a bed a material to be granulated or agglomerated as in one closed chamber. By passing a heated gas, for example, air, through a distributor plate, through the bed and the bed is "fluidized" in the chamber. If powder in the Material is suitably mixed and fluidized, becomes a liquid, which may or may not contain other functional components typically added above the bed arranged spray nozzle. For other processes, the Nozzle below be arranged of the bed. If the desired granular properties are achieved, the spraying the liquid interrupted, but the fluidization is maintained until by drying the desired product moisture content has been achieved. While the spraying process the controllers have a thermodynamic balance between the rate of adding and the rate of taking out liquid from the system Episode.

During the Drying dictates the removal of liquid from the granules Process. conventional Fluid bed processing in the pharmaceutical industry and the equipment used is described in "Air Suspension Technique of Coating Drug Particles "by Dale E. Wurster, D.E. J. Am. Pharm. Assoc. Sci. Ed. 1959, 48 (8), 451-454, and "Preparation of Tablet Granulations by the Air Suspension Technique "by Dale E. Wurster, D. E. J. Am. Pharm. Assoc. Sci. Ed. 1960, 49 (2), 82-84, whose Revelations are incorporated herein by reference.

• • Strömungsrate des Fluidisierungsgases (typisch Kubikfuß pro Minute, cfm, oder Kubikmeter pro Stunde, cmh) durch das Produktbett (Fluidisierungsgas);
• • Taupunkt des Fluidisierungsgases;
• • Temperatur des Fluidisierungsgases;
• • Gelöste Feststoffe in der Granulierungsflüssigkeit;
• • Anwendungsrate der Granulierungsflüssigkeit (Sprührate);
• • Temperatur des aus der Anlage ausströmenden Fluidisierungsgases (Auslaßgastemperatur); und
• • Temperatur des Produkts während des Prozesses.

In fluid processing, the typical parameters used for control are:

• Flow rate of the fluidizing gas (typically cubic feet per minute, cfm, or cubic meters per hour, cmh) through the product bed (fluidizing gas);
• Dew point of the fluidizing gas;
• • temperature of the fluidizing gas;
• • dissolved solids in the granulation fluid;
• Application rate of the granulation fluid (spray rate);
• The temperature of the fluidizing gas flowing out of the system (outlet gas temperature); and
• • Temperature of the product during the process.

Only by combining suitable values of these factors can suitable granules be produced. Since thermodynamics determines process flow, environmental equivalency can be used to monitor gas flow rate, dew point, temperatures, and spray rate by making the appropriate adjustments, as any of these parameters change during the process, to design and control that process.

In In this process, the flow rate of the Fluidizing gas sufficient to the bed adequately fluidize. Therefore, it is necessary to increase the flow rate of the fluidizing gas measure to calculate an EE value. The flow rate of the fluidizing gas, the dew point of the fluidizing gas, the temperature of the fluidizing gas and the spray rate are possible parameters, the measured and changed can be to a desired EE value or a desired Range of EE values.

at Fluid bed processing can become the method of characterization the desired EE value different from those used in tablet film coating is applied. For example, in tablet film coating AQL (acceptable quality limit) used to measure product quality and to match the product quality a desired one Range of EE values. For fluid bed granulation, particle size distribution, Moisture content or a drug release profile (if a release delay material applied to the powder) can be used to measure product quality and a desired area of EE values.

After a desired range of environmental equivalency values has been selected, the area preferably becomes an EE calculator / control unit 106 programmed as related to 1 has been described. The controller can work in a similar way as the one in 2 shown routine. For example, the spray rate, the gas flow rate, and the gas temperature may each be set to an initial value. The fluid bed processing operation may then be started using the initial values. As more particles are agglomerated, new values for the spray rate can be calculated and applied to the process to maintain the desired range of environmental equivalency values. Alternatively, new gas flow rate and temperature values may be calculated and applied to maintain a desired environmental equivalency value. The spray rate, gas flow rate or gas temperature can be applied to with reference to 3 be calculated manner described. Thus, the environmental equivalency based control systems of the present invention can be used to maintain product quality in fluid bed processing of pharmaceutical compositions in the drug manufacturing industry or other industries.

Capture fatal errors using environmental equivalency

According to one In another aspect, the present invention has a routine for Detecting fatal errors. The fatal error detection routine detected, that due a fatal error, such as a device malfunction or a natural one unhappiness one or more process parameters associated with an evaporation drying process exceed acceptable workspaces. For example, if in a film coating process the pump, the nozzle the process fluid supplies, fails, a fatal error has occurred and the process should be stopped and / or an operator should be alerted. In conventional Evaporation drying processes, there was no mechanism, the one automatic shutdown of a process based on environmental equivalency allowed. Therefore needed conventional Evaporation drying processes a constant monitoring by technicians, who decide if there is a fatal error. The present Invention reduces these difficulties in that on the Basis of environmental equivalency It is decided whether a fatal error has occurred.

4 FIG. 10 is a flow chart showing an exemplary fatal error detection routine according to the present invention. FIG. In the 4 The steps shown may be performed by a controller, such as a programmable logic controller, a computer, or any other hardware combination, software combination, or combination of hardware and software used to control an evaporation process.

In step ST1, the fatal error detection routine calculates an EE value based on measured process parameters. The process parameters may be spray rate, dew point, inlet gas temperature, inlet gas flow rate, and percent solids of the solution / dispersion. The EE value can be calculated using the equation described above. In step ST2, the fatal error detection routine compares the EE value with a safe operating range of EE values. The safe work area can be determined experimentally based on product quality analysis or previous machine failures. The safe working area is preferably wider than the area for which EE values are controlled, as in 3 is shown. In step ST3, the fatal error detection routine determines whether the safe work area has been exceeded. If the calculated EE value is greater than the upper range limit or less than the lower range limit, the fatal error detection routine takes appropriate actions for fatal errors (step ST4). For example, the fatal error detection routine may trigger an audible or visual alarm and / or disable the currently running process. Because the fatal error detection fatal error detection routine detects environmental fatality, multiple process parameters can be monitored simultaneously with reduced human intervention.

Manual calculation of Environmental equivalency and / or Adaptation of control parameters

Although the present invention is preferably implemented as an automatic control system for controlling an evaporation drying process using environmental equivalency, the present invention is not limited to such an embodiment. For example, in an alternative embodiment, process parameters may be manually adjusted by a technician based on environmental equivalency. For example, a technician may take steps similar to those in 2 to manually adjust process parameters to maintain a desired range of environmental equivalency values. The technician can monitor process parameters via a man-machine interface. Based on the process parameters, the technician can calculate the environmental equivalency value for the process. The calculation of the environmental equivalency value can be done manually or automatically. For example, the technician may calculate the environmental equivalency value using a spreadsheet (electronic worksheet) or other computer program suitable for calculating environmental equivalency, using a computing device or using pencil and paper. The technician may then manually adjust one or more process parameters to maintain the environmental equivalency value within the desired range of environmental equivalency values. In accordance with the process to be monitored, the technician can recalculate environmental equivalency at regular intervals and readjust process parameters. Any combination of manual and automatic adjustment of control parameters and calculation of environmental equivalency is within the scope of the invention.

Application of an environmental equivalency based control on other industries

As mentioned above, are the methods and systems for controlling evaporation drying processes using environmental equivalency not limited to drug production processes. An application of one environmental equivalency based control, as described above, on any industry, which has evaporation drying processes is in the field of Invention. The following sections describe other industries, have the evaporation drying processes, and how environmental equivalency can be used to process efficiency in any of the industries to increase.

Food- and confectionery processing

The Food and confectionery processing industries and the pharmaceutical industry have many processes in common.

For example Milk powder is produced using spray drying. Therefore, the methods and systems for applying a method described above environmental equivalency based control on spray drying used to be spray dried Produce food products, such as milk powder.

Confectionery production, such as candy manufacturing, may also have common processes with the drug manufacturing industry. For example, m & m ^{® are} film-coated. The methods and systems for applying environmental equivalency based control as described above for tablet film coating can therefore be applied to confectionery production.

Chemical and petrochemical processing

Synthetic or isolation techniques, for example, those that isolate or purify organic solvent extractions, use evaporation processes to isolate desired components. Examples of chemical or petrochemical products that utilize evaporation processes include, but are not limited to, polymers, peptides, organic hydrocarbons, fossil fuels. These products can be produced using a fractional distillation system. A fractional distillation system comprises, in series, a still, a fractionation column, a condenser, and a receiver. A material whose purification is desired, for example crude oil, is heated in the still. The heated material generates a gas. The gas rises up the fractionation column. From the fractionation column, the gas enters the condenser where the material is cooled to form a liquid. Part of the liquid is returned to the fractionating column and the remaining liquid is collected in a collecting tank collected. The distillation process may be continuous or intermittent. In a continuous process, the distillation flask is continuously charged with material to be cleaned. In an intermittent process, material is cleaned batchwise.

A on environmental equivalency based control can be applied to a system for fractional distillation be applied to optimal process parameters, for example Steam flow rate, Temperature and feed rate to determine. For example, can by monitoring the product quality, e.g. by measuring the purity, a desired environmental equivalency value for one continuous distillation process can be determined experimentally. After the desired Environmental equivalency value can be determined, one or more process parameters using the EE computer / control unit described above be controlled to this value or a predetermined range of values, even if another or change several other process parameters.

Textiles and foil goods

Environmental Equivalence can be used to control the application of liquids or suspensions to woven or nonwoven fabrics or other materials in a free air stream. Examples of liquids or suspensions that may be applied in this manner include polytetrafluoroethylene (PTFE), liquid crystals, water-repellent single-surface material. Since these processes involve spraying from one material to another material in a free air stream, these processes can be controlled in a manner similar to a tablet film coating as described above. Thus, with reference to 1 to 3 described, based on environmental equivalency control system on textile and sheet goods manufacturing processes that have spray applied.

Semiconductor manufacturing

In semiconductor fabrication, thin layers of dielectric, such as SiO ₂ , Si ₃ N ₄ , etc., polysilicon and metallic conductors are deposited on a wafer surface to fabricate devices and circuits. The techniques used to apply these layers are chemical vapor deposition (CVD) and physical vapor deposition (PVD). One method of performing a PVD deposition is to heat the coating material in a vacuum so that the coating material evaporates. The wafer or substrate is disposed in a holder near the source of the coating material to facilitate deposition of the vaporized particles on the substrate. An environmental equivalency value for PVD can be determined by analyzing the quality of the finished coating, for example density or uniformity. After a desired EE value has been determined, one or more process parameters may be controlled to maintain the desired EE value or range of EE values. For example, because the evaporation rate controls the amount of coating material in the atmosphere around the substrate, the evaporation rate and / or exposure time may be changed to maintain the desired EE value or range of EE values. The calculator / control unit described above may be used to maintain the calculated environmental equivalency value within the predetermined range. The control parameter calculation routine described above may be used to calculate the desired evaporation rate.

at CVD deposition, layers are deposited on a substrate, wherein reactive gases and an energy source are used to form a to generate chemical vapor phase reaction. The growth rate of the material on the surface of the Substrate can be controlled by controlling the substrate temperature become. As with a PVD deposition, a desired EE value by monitoring the quality of the finished product. The EE computer / control unit described above Can be used to provide values for temperature and / or exposure time to change, to a desired Environmental equivalent value or Range of environmental equivalence values maintain.

Lacquer layers, photographic Films and adhesive application

The Application of spray coatings, For example, painting or metallizing, in a free air flow is based on similar Principles such as a tablet film coating as described above. Thus, you can on environmental equivalency based systems are used to process parameters, for example the spray rate, to similar ones To control the manner as above for tablet film coating is described. examples for Coating processes using environmental equivalency can to a desired quality of the finished product include varnishing, photographic Film layers, polymer coatings and manufacture of building materials, for example However, oriented sheets of oriented fibers (OSB) are produced not limited to this.

environmental applications

environmental equivalency Can be used to bring in liquids in gas streams to control and / or eliminate special contaminants clarification to increase. examples for Applications of one on environmental equivalency include chimney gas cleaners, cooling towers, steam boiler feed air flow, but are not limited to this. For example, in Spray Scrub a liquid, For example, water, sprayed into a tower, in which a gas up which contains the contaminants whose elimination is desired. The contaminants are moistened by the water and fall to the bottom of the chamber, where they are eliminated. A desired one Environmental equivalent value or Range of values can be for the gas purification process through Measuring the quality of the dispensed product, e.g. the percentage of contaminations in the air flowing out of the tower, be determined. After a desired value or range of Values have been determined, the spray rate can be controlled to the wished EE value or range of EE values in the same way as above with respect to spray-drying described, uphold.

Claims (21)

Evaporation drying system with a computer / control unit, which has: (a) means for continuously receiving measured values for the temperature of the inlet gas, the dew point, the gas flow rate and the spray rate in an evaporation drying process; (b) a device for calculating an environmental equivalency value for the evaporation drying process on the Base of measured values; and (c) an output device a control signal to change one or more parameters related to the evaporation drying process the environmental equivalency value within a given range. An evaporation drying system according to claim 1, wherein the device is adapted to output a control signal, to a control signal to change the spray rate in the evaporation drying process. An evaporation drying system according to claim 2, comprising means for calculating a spray rate value by the environmental equivalency value within a given range. An evaporation drying system according to claim 1, wherein the device is adapted to output a control signal, to a control signal to change the temperature of the inlet gas in the evaporation drying process. An evaporation drying system according to claim 1, wherein the device is adapted to output a control signal, to a control signal to change the flow rate the inlet gas issue. An evaporation drying system according to claim 1, wherein the device is adapted to output a control signal, to a control signal to change of the dew point. An evaporation drying system according to claim 1, wherein the device is adapted to output a control signal, to a control signal to change percent solution / dispersion solids to spend a material to be sprayed in the evaporation drying process. An evaporation drying system according to claim 1, wherein the device for receiving continuously, the device for calculating and the means for outputting a programmable logic controller (PLC). An evaporation drying system according to claim 1, wherein the device for receiving continuously, the device for calculating and the means for outputting comprise a computer. An evaporation drying system according to claim 1, wherein the evaporation drying process aqueous film coating process is and wherein the means is adapted to output a control signal, to issue control signals to the environmental equivalency value within a Area of about 3.7 to no more than about 5.2 for the aqueous film coating process. An evaporation drying system according to claim 1, wherein the evaporation drying process aqueous film coating process is and wherein the means is adapted to output a control signal, to output control signals to maintain an environmental equivalency value of about 4.4 for the aqueous film coating process. An evaporation drying system according to claim 1, wherein the evaporation drying process Tablet film coating process is. An evaporation drying system according to claim 1, wherein the evaporation drying process Spray drying process is. Evaporation Drying System to An claim 1, wherein the evaporation drying process is a fluid bed granulation or agglomeration process. An evaporation drying system according to claim 1, wherein the evaporation drying process is pharmaceutical manufacturing process. An evaporation drying system according to claim 1, wherein the evaporation drying process Food or confectionery manufacturing process is. An evaporation drying system according to claim 1, wherein the evaporation drying process chemical or petrochemical isolation or purification process. An evaporation drying system according to claim 1, wherein the evaporation drying process Coating process for textiles or foil goods. An evaporation drying system according to claim 1, wherein the evaporation drying process Deposition process in a semiconductor manufacturing process. An evaporation drying system according to claim 1, wherein the evaporation drying process Coating process is. An evaporation drying system according to claim 1, wherein the evaporation drying process Contamination elimination process is.