THERMODYNAMIC PARAMETERS OF MEDICINAL GRANULATES

G. M. Kudryavtseva, G. N. Borisov, and V. N. Egorova

UDC 615.453.3.011.3:536

The coefficients of heat and mass transfer of a substance determine the basic laws of processes of drying colloidal capillary-porous materials. They characterize the capacity of the material for absorbing and giving up moisture. Their numerical values are necessary for performing calculations of the kinetics of heat and mass transfer in drying devices.

The motive force of transfer in colloidal capillary-porous materials which include medi- cinal granulates, is the difference in the potentials of mass transfer. In a state of thermodynamic equilibrium of the material being dried and the surrounding medium, the poten- tial of the whole system at any point is the same and there is no transfer of moisture. In the region Of the hygroscopic state the potential of mass transfer is represented by the chemical potential ~, which is defined by the equation [i, 2]:

= RT In r (1)

where R is the universal gas constant (in J/mole.K); T is the temperature of the air (in ~ and ~ is the relative humidity of the air (in %).

The chemical potential of moisture in the form of vapor is a function of the moisture content and the temperature of the granules. Consequently, for its determination the hygro- scopic properties of the granulates being dried must be known. The equilibrium moisture con- tent of the granules depends on the chemical composition of the initial medicinal powders and the relative humidity and the temperature of the air. Its values for various granulates

TABLE i.

Granulate

Amidopyrine Asfen Besalol Dibasol Liquorice root Rhubarb root Sodium p-

amino- salicylat e

Papaverine ffy~rochtoride

Dry extract of tselladonna

Urotropin r o s a l

Phenacetin

Thermodynamic Parameters of Medicinal Granulates

Range of change of the thermodynamic parameters, at relative at- mospheric humi ties from 0.1 o 0.gi_____ _ _ _ _

le ""b " Itrue specific iso- thermo a-- t Irlflol~clmean spe- q mn rtum therm.al rnass gr men " " ' oth

moisture content c o e f f i c i e n t 6 o �9 , ~ n ' a } - r ~ s s e r - W kolk- capaclty C m p �9 i0 4, 1/K { -- I ' ~" ~ 109, mole/J capaclty Crop

I 11o', mote/j

0,003...0,008 0,009...0,020 0,00l...0,016 0,002...0,011 0,030...0,016 0.024...0,180

0.026...0.070

0.007...0,025

0,016...0,041 0,003...0,014 0,002...0,012 0.003,.0,015

0,355...5,800 0,708...19,440 0,425..18,850 0,787..12,800 9,610..80,700

13,100..74,460

3.980..39,583

1.060..25.862

1,560..32,800 0,444..54,000 0,550..25,000 0,464...7,292

0,067...0,109 0,135...0,367 0,081...0,356 0,190...0,242 1,825...1,526 2,490...1,410

0,756...0,748

0,201...0,489

0,291...0,620 0,084...2,132 0,104...0,483 0,088...0,138

1,616 5,310 5,250 4,415

35,839 40,490

15,480

6,400

9,600 8,530 5,600 3,520

Leningrad Institute of Pharmaceutical Chemistry. Translated from Khimiko-Farmatsevti- cheskii Zhurnal, Vol. ii, No. 4, pp. 95-97, April, 1977. Original article submitted July 7, 1976.

This material is protected by copyright registered in the name o f Plenum Publishing Corporation, 227 West 1 7th Street, New York, N. Y. 10011. No part o f this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming, recording or otherwise, wi thout written permission o f the publisher. A copy o f this article is available f rom the publisher for $ Z 50.

532

j~,16SJ/mole

4o!

2O

0 I I 1 t 0,005 0,0',0 0 ,015 0,020 W

Fig. i. Dependence of the chemical poten- tial of mass transfer on the equilibrium moisture content of medicinal granulates in the hygroscopic regions, i) Besalo! [A~ropa belladonna and phenyl salicylate (1:30)]; 2) dibasal [Bendazol hydrochlor~ ide]; 3) urosal [mixture of methenamine and phenyl salicylate]; 5) asfen [acetyl- salicylic acid and aeetophenetidine (5:3)]; 6) papaverine hydrochloride.

determined by the tensimetric method have been taken from the literature [3]. Figure ! gives the relationships between the equilibrium moisture content and the chemical potential of mass transfer for a number of granulates calculated from Eq. (i).

A quantitative characteristic of the bond of moisture in colloidal capillary-porous materials is the true specific isothermal mass capacity Cm~:

where W i s the m o i s t u r e c o n t e n t o f t h e g r a n u l e s ( i n k g / k g ) .

The v a l u e o f t h e t r u e s p e c i f i c i s o t h e r m a l mass c a p a c i t y f o r m e d i c i n a l g r a n u l a t e s was c a l c u l a t e d by t h e g r a p h i c a l d i f f e r e n t i a t i o n of t h e c u r v e s shown in F i g . 1. The t r u e s p e c i f i c i s o t h e r m a l mass c a p a c i t y d e t e r m i n e d t h r o u g h t h e c h e m i c a l p o t e n t i a l o f mass t r a n s f e r i n c r e a s e s w i t h a r i s e in t h e m o i s t u r e c o n t e n t o f t h e g r a n u l e . C o n s e q u e n t l y , i t s mean v a l u e was used i n t h e c a l c u l a t i o n s .

The change i n t h e m o i s t u r e c o n t e n t o f t h e g r a n u l e s under t h e a c t i o n o f t h e t e m p e r a t u r e i s c h a r a c t e r i z e d by t he t h e r m o g r a d i e n t c o e f f i c i e n t 6p:

6n = Cm~ ( 0 ~ (3)

where d~/dT i s t he t e m p e r a t u r e c o e f f i c i e n t o f mass t r a n s f e r ( i n J / m o l e ) .

The t e m p e r a t u r e c o e f f i c i e n t s o f mass t r a n s f e r were o b t a i n e d by t h e g r a p h i c a l d i f f e r e n t i - a t i o n o f t he c u r v e s o f t h e dependence of t h e c h e m i c a l p o t e n t i a l o f mass t r a n s f e r on t h e a i r t e m p e r a t u r e ,

T a b l e 1 g i v e s t h e i n i t i a l and f i n a l v a l u e s o f t he e q u i l i b r i u m m o i s t u r e c o n t e n t and t h e v a l u e s o f t h e t r u e s p e c i f i c i s o t h e r m a l mass c a p a c i t y Cm~, t h e t h e r m o g r a d i e n t c o e f f i c i e n t ~p, and t h e mean s p e c i f i c i s o t h e r m a l mass c a p a c i t y Cm~ c o r r e s p o n d i n g to them f o r a s e r i e s o f m e d i c i n a l g r a n u l a t e s a t t h e r e l a t i v e a t m o s p h e r i c h u m i d i t i e s ~ = 0 .1 and ~ = 0 . 8 . At a c o n - s t a n t temperature, the chemical potential of mass transfer and the true specific isothermal mass capacity rise with an increase in the moisture content of the granules. The mean spe- cific isothermal mass capacity for medicinal granulates changes within wide limits, the high- est values being found for granulates of plant origin.

The nature of the change in the thermogradient coefficient as a function of the equilib- rium moisture of the granules depends on the form of the binding of the moisture of the material and the type of transfer of the substance. In the region of small values of mois- ture contents, the thermogradient coefficient increases for the granulates investigated. At high values of the moisture content for the liquoric root, rhubarb root, sodium p-amino- salicylate, and phenacetin granulates it decreases, and for the other granulates it approxi- mates to constancy or increases somewhat.

The figures given in Table 1 can be used for analyzing drying processes and for calcu- lating processes of heat and mass exchange in layers of medicinal granulates with different

533

moisture contents. More accurate values of the thermodynamic parameters of medicinal gran- ulates at various intermediate values of the relative atmospheric humidity can be obtained in the Leningrad Institute of Pharmaceutical Chemistry.

LITERATURE CITED

i. A.S. Ginzburg, Principles of the Theory and Technique of Drying Food Products [in Russian], Moscow (1973).

2. L.M. Nikitina, in: Tables of Mass Transfer Coefficients of Moist Materials (ed. by A. V. Lykov) [in Russian], Minsk (1964).

3. V.I. Gorodnichev, V. I. Egorova, and G. N. Borisov, Khim. Farm. Zh., No. 7, 47 (1972).

EXPERIMENTAL-STATISTICAL DETERMINATION OF THE VOLATILITY OF

PHARMACEUTICAL CHEMICALS

V. S. Shul'man, I. I. Dozorova, and E. V. Liberman

UDC 615.011.3:536.42

The study of the toxic properties of pharmaceutical chemicals is associated with the analysis of the atmosphere, since the main route for the penetration of harmful substances into the organism is the respiratory route. An important role in the analysis of air is played by the method of sampling, which is determined by the state of aggregation of the sub- stances being analyzed. Many substances are present in the air in the forms both of aero- sols and of vapors. The presence of the latter permits an estimate of the volatility of the substances -- a magnitude characterizing the maximum vapor content at a given temperature in equilibrium with the condensed phase. Volatility is expressed in milligrams per liter or per cubic meter. There is no information in the literature on the volatility of pharmaceut- ical chemicals. Direct determination of volatility experimentally at temperatures of 0-40~ is difficult or completely impossible because of its low values for solid intermediates and final products (of the order of I0-7-I0 -~ mg/liter); it is frequently impossible to determine accurately such concentrations of substances by existing analytical methods.

Methods of determining volatility by calculations based on known relationships of the pressure of saturated vapors over solid or liquid substances on the temperature (the equa- tions of Antoine, Riedel, Miller, and others) [I] require the use of constants which are un- known for the majority of pharmaceutical chemicals.

In the present work, to determine the volatility we have used experimental-statistical prediction, experimentation being performed in the range of elevated temperatures (50-150~ where the volatilities can be measured by existing methods, the range of possible values of volatility at temperatures of 0-40~ then being predicted by extrapolating the results ob- tained.

Let us consider the experimental-statistical prediction of the volatilities of sub- stances in the light of general questions of prediction.

Below we give the structural scheme of the prediction of volatility. In this scheme, dotted arrows denote calculating operations and full arrows experimental operations. As can be seen from the scheme given, the key question for prediction is the model of the predic- tion of volatility. To find the volatility it is first necessary to perform all the experi- mental and calculating operations shown in Fig. i.

Branch of the S. Ordzhonikidze All-Union Scientific-Research Institute of Pharmaceutical Chemistry, Moscow Oblast. Translated from Khimiko-FarmatsevticheskiiZhurnal, Vol. Ii, No. 4, pp. 97-101, April, 1977. Original article submitted August 30, 1976.

This material is protected by copyright registered in the name o f Plenum Publishing Corporation, 227 West 1 7th Street, New York, N. Y. 10011. No part o f thispublication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming, recording or otherwise, wi thout written permission o f the publisher. A copy o f this article is available from the publisher for $7.50.

534