SU1744649A1 - Method for measuring moisture of biosynthesis products and medical preparations in vacuum and device - Google Patents

Abstract

Purpose: The method for measuring the moisture content of biosynthesis products is used for dehydration in the volume of semi-industrial and industrial freeze drying plants. The purpose of the invention: improving the accuracy and expanding the range of moisture measurement. SUMMARY OF THE INVENTION: A method for measuring the moisture content of biosynthesis products consists in measuring the temperature difference between a coolant and a coolant supplied to a product placed in a vacuum chamber that is pre-evacuated, and determining the total amount of heat released during freezing and the total amount of heat spent on moisture sublimation, taking into account the difference of their phase transformations, and the current humidity is determined from the relation: W (t) Q s - Q s (g) - / 0 s, where gs C is the phase transformation heat freezing liquid during freezing, kJ / kg; gf — heat of the phase-hog transformation of ice-water into vapor during suolimation, kJ / kg; OS (g) is the total current value of the heat spent on the sublimation of moisture of the frozen product, kJ; Oz, the amount of heat released during the freezing of moisture and transferred to the coolant, kJ. 2 sec. f-ly, 4 ill. sl C

Description

The invention relates to medicobiological equipment.

At present, there are no fairly simple and reliable methods for obtaining generalized continuous information on the course of the dewatering process in the volume of semi-industrial and industrial freeze-drying plants.

There is a known method for measuring the moisture content of biosynthesis products and medical preparations in vacuum by changing the capacitance of the dehydrated product. The receipt of a given humidity in a product is judged by the magnitude of the ohmic resistance that has reached a given value.

The device carrying out this method contains two electrodes placed at a fixed distance from each other, between which the dried product is placed. The electrodes are included in the shoulder of the bridge circuit, and the sensor is connected to the secondary device (recorder).

The disadvantages of the method and device for its implementation are low measurement accuracy, since they can be used at a residual moisture content of not less than 10%, while the humidity of medical preparations upon completion of dehydration in most cases should not exceed 1-3%; when using this method, the error in 15-20% is considered quite

vi

i

J o

normal; there are cases of product detachment from the electrode surface, which excludes the possibility of further measuring the moisture content of the product being dried, the quality, nature of the product, as well as possible chemical and other impurities in it, have an important measurement accuracy; a narrow range of measurements, since they cannot be used in determining the humidity of the frozen (frozen) product; the method is not integral, since it is impossible to measure the current average humidity in the volume of the product being dried, and it is possible to measure only local, i.e. at the location of the resistance sensor; the presence of electrical wires connected to the electrodes creates additional heat influxes, which leads to a lower moisture content of the product between the electrodes.

A barometric method for measuring the moisture content of a product in vacuum is also known. The method is based on the periodic shut-off of the valve in the evacuation path of vapor and non-condensable gases, which allows judging by the rate of pressure change in the sublimator about the value of the residual moisture of the dried product.

A device implementing this method contains a residual pressure sensor electrically connected to a vacuum gauge (or recorder) and a timer.

The disadvantages of these methods and devices for its implementation are low measurement accuracy, since they do not allow to determine the residual moisture of the product with its value less than 10%. The accuracy of measuring the humidity of 15-25% is considered good. A slight violation of the tightness of the installation leads to a decrease in the quality of the finished product (its drying) or a significant increase in the duration of the process, as well as measurement error; narrowness (limitation) of the range of use, since the method cannot be used in installations with sublimator and desublimator combined in one case (for example, the Friger plant, CSFR), and in all types of installations during the freezing process, significantly affects the quality of the product (reduces its quality), since a cyclic change in the residual pressure in the sublimator leads to a corresponding increase in the pressure in the sublimator, thawing of the product and, as a consequence, the release of the product into the volume of the sublimator and lowering NIJ activity of the final product.

It is also known a device for measuring the humidity during freezing in vacuum of medicinal solutions and products of microbial synthesis,

There is a known method for measuring the moisture content of biosynthesis products and medical preparations during freezing in terms of heat flux, which forms the basis of the prototype device,

The device comprises a freezing chamber with a control unit inside which a plate with an integrated measuring cell fitted with a heat flow sensor and a temperature sensor are installed through a multiplier unit connected to the recorder. This device further comprises a reference cuvette with a second heat flux sensor inversely connected with the first heat flux sensor and

connected to a null-organically connected, polarized relay, second multiplication unit, integrator and divider, output connected to the second recorder input, resistance sensor, through a third multiplication unit connected to the third recorder input, differentiator, output connected to the second polarized relay input and the entrance to the exit of the zero-body, the fourth entrance

the recorder is connected to the output of the second multiplication unit.

The disadvantages of this device include a narrow measuring range, since moisture can only be measured during the freezing process.

The purpose of the invention is to improve the accuracy and expand the range of moisture measurement.

The goal is achieved by the fact that

In the method for measuring the moisture content of biosynthesis products and medical preparations in vacuum, the temperature difference between the incoming and outgoing coolant and heat carrier fluxes is measured by the magnitude of the heat flux,

determine the total amount of heat released during freezing, and the total amount of heat from the onset of dehydration, which went into sublimation, taking into account the difference in their phase transformations, and the current moisture content of the product W (r) is determined from the ratio

Q3-Qc (T) -p

W (r)

where gz is the heat of phase transformation of the liquid during freezing, kJ / kg;

rc is the heat of ice-water phase transformation into vapor upon sublimation, kJ / kg;

Qo (f) is the total current value of heat, which went to the phase transformation during the sublimation of moisture from the frozen product, kJ;

Oz is the amount of heat released during the freezing of moisture in the product and transferred to the coolant, KJ.

In an apparatus for carrying out this method, comprising a sublimation chamber connected to a vacuum source, inside which are placed plates with product tanks mounted on them, equipped with circulation channels for heat and coolant and forming a circulation loop, a heat flow sensor electrically connected with the first multiplication unit, equipped with a setting device and an output through a polarized relay, an integrator and a first divider input connected to the recorder, a capacitive sensor installed in the product and through a differentiator connected to the second input of a polarized relay, as well as containing a second integrator, a second and third multipliers with set points. The device additionally contains a two-position switch, the input through the second multiplication unit connected to the output of the first multiplication unit, one of the outputs connected to the input of a polarized relay, and the second output through the second integrator and the third multiplication unit connected to the second input of the divider, and the memory unit installed between the first integrator and the divider, with the first output of the memory block additionally connected via a differential circuit to the second input of the divider, and its second output to the second input of the recorder At the same time, a heat flow sensor is integrated into a thermal gradient meter, made in the form of a thermally insulated chamber, included in the heat and coolant circulation circuit in a sublimation chamber with two closed sections of high heat conducting material, coupled with a heat flow sensor, one of the sections being connected to the inlet and the other with the outlet connections of the heat and coolant circulation loop in the sublimation chamber.

Figure 1 shows a diagram of a device for measuring the humidity of biosynthesis products and medical preparations in vacuum; FIG. 2 shows calibration values of the dependence of the thermopower of a thermal gradient meter with a heat flux sensor built into it on the temperature difference between heat and coolant; Fig. 3 is a sequence diagram of the operation of the elements of the device circuit during freezing and sublimation; 4 shows freezing curves and

drying ginseng, obtained in accordance with the proposed method (using the proposed device) and in accordance with the barometric measurement method

humidity.

The method for measuring the moisture content of biosynthesis products and medications in vacuum is carried out as follows.

It is known that the process of sublimation dehydration consists of two independent interrelated processes: freezing of the product and its sublimation dehydration in vacuum. It is known that during freezing of moisture in the product, for each kilogram of moisture, 80 kJ of heat is released, i.e. kJ / kg At the same time, for the sublimation of ice-water to vapor in vacuum, it is necessary to bring 716.4 kJ / g of

warmth.

When the product is frozen in vacuum due to its heat capacity, a part of the moisture evaporates and sublimates into the volume of the sublimation chamber. This part of the moisture is

from 10 to 20% and further when measuring the current humidity is not taken into account, since the thermogradiometer passes with the refrigerant only that amount of moisture that remained in the product in the frozen

the form, i.e. Oz

From this it follows that the amount of heat released during freezing of moisture in the volume of the sublimation chamber will be less than the amount of heat required

on sublimation of the same amount of moisture in 716,, 955 times.

Taking into account that the mass of frozen moisture is equal to the initial mass of moisture that is subject to sublimation in the product, the definition

the specific humidity (i.e., reduced to a mass of 1 kg) does not make sense and only complicates the general scheme of the device.

Thus, when the coolant is circulated through the channels of the plates installed in the sublimation chamber, the heat of phase transformation is released from the product being frozen, which, having passed through the plates, is transferred to the coolant and heats it. Gradient formed

temperature is fixed by thermogradientomer. Knowing the temperature gradient At (r) and its consumption, determine the specific heat release p3 (t) phase transformation (crystallization of moisture, i.e.)

dz (t) stz At (r), (1)

During the freezing of the product, the total amount of heat Oz released during the crystallization of moisture during the Ats TK-TH time is

TЈrЈ

 q3 (t) dr cm3k / U3 (r) dr. (2)

THTH

During sublimation dehydration, the product is continuously supplied with heat, the amount of which is different at different stages of drying. When removing free moisture (drying), the amount of freeze-dried moisture is proportional to the amount of heat added.

The amount of heat supplied to the product QC (T), and therefore the amount of freeze-dried moisture, is determined by the total amount of specific heat release QC (T) from the start of the dewatering process

R | t;

 qc (T) dr: cmck / Uc (t) dr.

Toto

Since freezing a certain amount of moisture releases 8.955 times less heat than the same amount of moisture is required to sublimate, the current moisture of the dehydrated product is found from the expression taking into account the difference between the heats of sublimation and crystallization, i.e.

Q, -o,

IVifJsc-

tS 1 /, r /,. iviciTJi

7H7, r

, / 4 ft c;

(h)

j

hh

m, J and, H) s / 1

Expression (3) is an algorithm for the operation of a device implementing the proposed method.

A device for measuring the moisture content of biosynthesis products and medical preparations in vacuum (Fig. 1) contains a sublimation chamber 1 connected to a source 2 of a dilution, inside which are placed plates 3 with containers installed on them with product 4.

The plates 3 are provided with circulation channels 5 for heat and coolant and, together with a peristaltic fluid pump 6, form a circuit 7 for the circulation of heat and coolant.

The device is equipped with a thermogradient meter 8, made in the form of a thermally insulated chamber, divided into two isolated sections 9 and 10. Section 9 is connected to the inlet 11 of the inlet part of the sublimator circulation circuit, and section 10 is connected to the outlet of the 12 sublimation circuit. cameras 1.

Between sections 9 and 10, a heat flow sensor 13 is electrically connected to them, electrically connected through a first multiplication unit 14 to a control unit 15,

5, a second multiplication unit 16 with a setting point 17; the first output of the on-off switch 18, the polarized relay 19, the integrator 20, the memory block 21 and the first input of the divider 22 are connected to the first input

10 registrars 23.

The second output of the on-off switch 18 through the second integrator 24 and the multiplication unit 25 with the setting device 26 is connected to the second input of the divider 22. To the same

Input 15 is additionally connected to the first output from the memory block 21.

The device is equipped with a capacitive sensor 25 installed in the product 4, which through the differentiator 28 is connected to

20 to the second input of the polarized relay 19 (control input).

In determining the temperature gradient, the device uses a heat flux sensor designed by the Institute.

25 Technical Thermal Physics Academy of Sciences of the Ukrainian SSR. In such a sensor, up to 4-10 pieces of consecutively connected copper-constantan thermocouples are found per 1 cm2. The sensitivity of such a sensor (when using conventional measuring devices) is 1-1 - 6 ° C.

As a pump 6 for circulating refrigerant and coolant in the secondary circuit circulation system, it is better to use na35 soy with a fixed performance (for example, peristaltic), with several fixed costs (for example, five - from maximum to minimum) periodically in

40 of the drying process, taking into account the periods of dehydration of the product using a switch (not shown). Establish the required performance, thereby changing the power supply to the dried product.

45 Simultaneously with switching the pump capacity, the input to the multiplication unit 14 with the setting unit 15 receives a signal proportional to the flow rate of the heat carrier m in the circulation system. Such an organization

50 changes eliminate the need to install and use a flow meter in the secondary circuit, which greatly simplifies the overall design of the device. When freezing, the flow rate of refrigerant 55 in the circulation system should be maximized. In addition, in the world practice, when using electric heaters, when heat is supplied to the shelves, only three fixed powers are used, while we have five and not

it is difficult to increase their number if necessary.

The device works as follows.

Since the heat capacities of the coolant and coolant due to the temperature difference are different in the fourth character (for example, for liquid R-100), its change can be neglected (when liquid is taken into account when adjusting the setting unit of the corresponding multiplication unit) and the value c is considered a constant value for a given flow rate liquids in the circulation circuit.

The obtained values of m are entered into the appropriate unit and, during operation of the plant, are occasionally checked and, if necessary, adjusted.

In addition, the measurement is preceded by the calibration of the measurement system (Figure 2). Calibration is carried out using an electric heater connected to the power meter and installed by any of the methods in the coolant circulation line in a fully assembled circuit, eliminating heat removal from the heater to the environment and providing conditions for the circulating flow, similar to the working flow.

Before measuring, before installing the pallets with the product on the shelves of the sublimation chamber 1, an experimental zero is measured, which differs somewhat from the zero value of the thermoelectric power C from the heat flux sensor 13 (friction in the channels of the plate 3, radiation heat supply, etc.). The resulting discrepancy is compensated or taken into account when determining the final result.

In the same tray with product 4, a capacitive sensor 27 is installed, the door of the sublimation chamber 1 is closed.

Freeze the product. In the process of determining the amount of frozen moisture, Oz in product 4 includes a peristaltic pump 6 of the secondary refrigerant circuit (the primary circuit forms a compressor) or two series-connected compressors that cool the intermediate between the primary and secondary circuits (in the heat exchanger). At the same time, a low-temperature coolant with a given flow rate, passes through section 9 of a thermogradiometer 5 with an inlet 11 of the inlet circulation circuit of the sublimation chamber 1 and cools one of the working surfaces of the heat flux sensor 13, enters the circulation channels 5 of the plate 3 and cools them.

In turn, due to the thermal conductivity of the plates, they are cooled to a negative temperature of the container with product 4, which leads to its freezing (phase transformation).

During the freezing process, each kilogram of moisture releases 80 kJ of heat, which is removed through the base of the pallet to the plates and then to the cold carrier. At the same time, the temperature of the coolant increases slightly.

Having passed through the circulation channels 5 of the working plates 3, the coolant enters section 10c with the outlet nozzle 12 of the output circulation circuit of the sublimator and heats its working surface coupled to the heat flux sensor 13. Due to the temperature difference in section 9 and 10 of the thermogradiometer 8, thermo-emf occurs, the value of which is proportional to their difference (Fig. 2), i.e. (At).

In the process of freezing, the signal from the heat flow sensor 13, having passed through the position s of the switch 18, is fed to the input of a polarized relay. The contacts are normally open. Simultaneously, from the resistance sensor 27, the signal is continuously fed to the differentiator 28 and then to the control input of the polarized relay 19.

It is known that at a constant product temperature its resistance is constant, and therefore the signal from differentiator 28 is O and the control input of the polarized relay 19 is not received, which prevents the signal from the heat flux sensor 13 to the input of the integrator 20.

In the case of heating the frozen product, the value of the ohmic resistance of the product falls. The value of the differentiated signal arriving at the control input of the polarized relay is negative, which also excludes the passage of the signal from the heat flow sensor 13 to the integrator 20.

When the product 4 is frozen, the resistance of the product increases. The signal from the output of the differentiator becomes positive. The signal goes to the second input of the polarized relay 19 (control input). The relay is activated and its working contacts are closed, which facilitates the passage of a signal from the heat flow sensor 13.

Passing through the polarized relay 19, the signal from the heat flow sensor 13, proportional to the intensity of the phase transformation (freezing), enters

integrator 20, where it is summed up, and its maximum value is stored by memory unit 21.

It is also known that if a wet product is completely frozen and then cooled, the value of its ohmic resistance remains almost constant (Fig. 3, p. 27). Therefore, after the product has been completely frozen, the signal value from the differentiator takes a zero value and the polarized relay 19 opens its contacts (operating).

The maximum signal from integrator 20, recorded by memory unit 21, will be directly proportional to the amount of frozen moisture in product 4 and corresponds to the value Oz. At this point, the freezing process of the product is completed and the sublimation process begins.

Sublimation product. Before the beginning of the sublimation of the product 4 in the setting device 26, a signal value is set that is proportional to the value (gs / gf) (80: 716.4) 0.1116694.

The two-position switch 18 is switched to position C and the circulation circuit 7 begins to deliver coolant with a predetermined temperature in the plate 3. When the coolant passes through section 9 of the thermal gradient 8, the corresponding working surface of the heat flux sensor 13 assumes the appropriate temperature. Then the coolant enters the circulation channels 3 and heats the latter. The heat from the plates 3 is spent on the sublimation of the material 4 mounted on the plates. The coolant is cooled. Passing through the second section 10 of the thermal gradient 8, the coolant is pumped by the pump 6 to the heat exchanger, where it is heated to a predetermined temperature, etc. during the entire period of freeze-drying.

Due to the temperature difference between the coolant entering the thermogradiometer 8 (section 9) and the temperature leaving it (section 10), thermoEMF occurs in the sensor 13, which is proportional to the temperature gradient. The signal passed through the blocks 14 and 16 with the control devices 15 and 17, is fed to the switch 18 in the form of dependence

qc (T) cmc At (r)

and further to integrator 24, where its value is summed by Oc (t). At the same time, the continuously increasing value of Oc (t) enters multiplication unit 25 and then into divider 22 as a dependence

wrt) V ° c

YU

L b

Value obtained after divider 22

(4) is the residual moisture content of the product being dried, which is continuously recorded by the recorder 22.

The dehydration of the product 4 ends when the signal reaches 22 in the recorder that corresponds to the specified humidity WL. At the operator’s command, the pump 6 is turned off. The volume of the sublimation chamber 1 is filled

gaseous nitrogen to equalize pressure with atmospheric. The containers with the product are sealed. The sublimator door is opened and pallets with the product are extracted from it.

PRI me R. When testing the method of measuring the moisture content of biosynthesis products and medical preparations in vacuum, ginseng biomass was used as the test product.

The control (initial, after freezing and after drying) humidity of ginseng was determined by thermogravimetric method, in accordance with which weighed weights of the total mass of the product

about 3,000 g (see tab., etc. 1.1), poured into calcined cups and dried to equilibrium moisture in a dry-air cabinet at 105 ° C. The initial moisture content of this product was determined by the formula, based on the weight of the released moisture from the product cooled in a desiccator.

(t 1 -t 9) 100 t 1 - t0

where mi is the weight of the sample before drying;

that is the weight of the sample after drying; t0 is the mass of the product without a product. Humidity of the product in all cases was taken as the average of 5 control measurements.

The resulting product was placed in 140 containers with a capacity of 40 ml. The containers were installed on the shelves of the freeze-drying chamber with a productivity of 6 kg / cycle on the initial product and frozen to -55 ° C, which is 1 ° C below the lower boundary of the eutectic zone. During the cooling process, the heat of crystallization of the moisture Oz in the product was determined using the proposed device. The data obtained are listed in a table (Section 2.2).

As follows from the analysis of the table, the error of the proposed method for determining the humidity differs from the method according to

GOST24061-80, does not exceed 3%, which is 1.5-3 times and more accurately known methods.

The method was tested on alcohol-related enzymes Pectofoetidine POh and Amylorizine POh (Rasskazovsky BHZ, contract 158–9.9D) and gave positive results.

Thus, the method for measuring the moisture content of biosynthesis products and medical preparations in vacuum and the device for its implementation can improve the measurement accuracy of products subjected to freezing and sublimation dehydration in semi-industrial and industrial plants by 1.5–2 times or more, expanding the range of use , account of the possibility of determining the humidity of both frozen and dehydrated products, as well as due to the possibility of determining moisture up to 0.5% instead of 3-10%.

Claims (3)

1. A method for measuring the moisture content of biosynthesis products and medical preparations in vacuum, including placing the product in a vacuum chamber, evacuating it, creating a heat flow through the product using coolant and heat carrier and measuring it, determining the heat released during freezing, which differs from in order to improve accuracy and range, measure the temperature difference between the coolant and the coolant, determine the total amount of heat released during freezing, and the total amount of heat rafts spent on the sublimation of moisture, taking into account the difference in their phase transformations, and the current humidity W (t) is determined from the ratio W (r) Q3-Qe -7 f GL where gs is the heat of phase transformation of the liquid during freezing. kJ / kg; rc is the heat of ice-water phase transformation into vapor upon sublimation, kJ / kg; Qc (f) is the total current value of the heat spent on the sublimation of the moisture of the frozen product, kJ; Oz - the amount of heat released during the freezing of moisture and transferred to the coolant, kJ. 2. A device for measuring the moisture content of biosynthesis products and medical preparations in vacuum, which contains a sublimation chamber connected to a source of discharge, inside of which plates are placed with these tanks, provided with circulation channels for heat and coolant and forming a circulation loop, a heat flow sensor electrically connected to the first multiplication unit, equipped with a setting device, and an output through a polarized relay, an integrator and the first input of a divider connected to the recorder, a capacitive sensor mounted to the second input of a polarized relay, and also comprising a second integrator, a second and a third multipliers with control knobs, characterized in that it additionally contains a two-position switch, the input through the second a multiplication unit connected to the output of the first multiplication unit, one of the outputs connected to the input of a polarized relay, and another output through a second integrator and a third multiplication unit connected to the second input of the divider, and a memory unit installed between the first integrator and the divider, the first output the memory unit is additionally connected via a differential circuit to the second input of the divider, and its second output is connected to the second input of the recorder, while the heat flux sensor is built into the thermal gradient meter, made in the form of a sealed chamber included in the circulation circuit of the heat and coolant in the sublimation chamber with two closed sections of high thermal conductivity material, coupled with a heat flux sensor, one of the sections is connected to the inlet, and the other is connected to the outlet of the circuit of the heat and coolant in the sublimation chamber. W cf 2. Frozen product 2.1.The amount of heat during the freezing is alive and pin L. L. EXTRACTLY make up ijrj CL (, 32%) QTi "0.020 8 2.2, The amount of heat released during the crystallization of moisture 8 product, determined from the proposed device, Q3, “Ls109, 2 3. The heat difference ( -0MSl8, t) 2., Humidity of the frozen pro LU "ta (calorimetric method) D (2.9 2.5. Humidity of the frozen product Jrocr Uol-HQ), 42.82 2.83 2.8 3, Dried product 3.1. Kolitsrgtgso heat of sublimation, k / Зж (with , k1zh / kg) 920, 3.2, Humidity of the dried product (calorimetric method),% 7.21 $ 34. Humidity of the final product (according to GOST 2 06180)% 7, FROM 3 .. Value moisture differences (points 3-2 and 3.3-) 0.22 3.5. % moisture difference when determining the proposed (calorimetric) method and according to GOST 2 061-802.96 gldadm iAAAMI If i KG SECOND I G TuPCHSh 1 j compressor Phie.1 //, /:  - -1 | 4 eight Fig 2. } - about CM from chCO sf rr) / / / 7 d) (.V n Schg  V  About ,, kJ / (kg.h) Stopping product R.JOM I G I (kg-h) 1 Sublympzioinoo ooozpozhivanis i I m & FIG.