You are on page 1of 5

Pharmaceutical Chemistry Journal

Vol. 36, No. 5, 2002

A POTENTIOMETRIC STUDY OF THE DISTRIBUTION OF CATIONIC SURFACTANT ANTISEPTICS IN WATER PHYTOSORBENT SYSTEMS
A. P. Podterob,1 V. V. Egorov,1 and E. I. Yankovskii1
Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 36, No. 5, pp. 33 36, May, 2002.
Original article submitted October 1, 2001.

Sorption technologies are finding increasing application in various fields, including chemistry, biochemistry, medicine, etc., owing to the reversibility, selectivity, and many other advantageous features of these technological processes. Sorbents of plant origin (phytosorbents) exhibit certain advantages over zeolites, activated coals, ion-exchange resins, and other materials. In particular, both fabrication and utilization of phytosorbents employ ecologically safe processes, which is especially important at present. Phytosorbents are relatively cheap: these materials can be obtained from various wastes of the agriculture and wood-processing industries. Many such phytosorbents (cellulose and its oxidized forms, lignin, peat, bog and peat musci, etc.) are widely used in medicine as absorbing and wound-healing materials in surgery, enterosorbents, and polymeric matrices for new drugs. Cationic surfactant antiseptics (SASs), representing for the most part higher quaternary ammonium salts of nonsymmetric structure, are referred to in pharmacy as inverted soaps and used for the preparation of antiseptic solutions [1]. An example is offered by 0.5% aqueous solution of chlorohexidine bigluconate a highly effective antiseptic preparation. However, a common disadvantage of surfactants such as chlorohexidine salts is their rather high toxicity. In connection with this, some recent investigations were devoted to the synthesis of new controlled-release preparations in which the acting substance is immobilized by molecular or exchange adsorption interactions in a polymeric matrix (carrier) and then gradually released so as to ensure a prolonged therapeutic action [2]. Typical carriers for SAS cations and other biologically active substances are cellulose and related modified products, such as monocarboxycellulose (MCC), carboxymethyl cellulose, and phosphate cellulose [2, 3]. Phytosorbents, being sorption-active materials with weak acidic properties (related to the presence of carboxy
1

and phenol groups) possess more or less pronounced detoxicant properties. An example of a highly effective detoxicant is offered by polyphepan a substance produced from lignin. The sorption activity of polyphepan with respect to heavy metal cations was reported in [4]. In this context, it was also of interest to study the sorption activity of polyphepan with respect to some other highly toxic agents: sorbed by polyphepan, such poisons could be eliminated from the organism. Cationic SASs, which can accidentally enter the stomach in the course of gargling of the oral cavity and throat with antiseptic solutions (e.g., 0.5% aqueous chlorohexidine bigluconate solution, Eludril preparation, etc.), also present a danger. The purpose of this study was to obtain new data on the distribution of cationic SASs in the water phytosorbent system, with the sorbent being represented by MCC, polyphepan, and musci(sphagnum). EXPERIMENTAL PART The experiments were performed with a series of sorbents including (i) MCC based on a commercial medicinal gauze with an exchange capacity of EC = 1.25 mg-eq/g, (ii) green parts of musci Sph. cuspidatum and Sph. fallax with EC = 0.74 and 1.02 mg-eq/g, respectively, (iii) sphacelated parts of Sph. cuspidatum with EC = 0.42 mg/eq/g, and (iv) medicinal enterosorbent polyphepan with EC = 0.13 mg-eq/g. The samples of sphagnum were collected at the Berezinskii State Biosphere Reserve (Belarus), identified by examination under a microscope [5], and dried to constant weight. The green (upper) and sphacelated (lower) parts were separated and ground in a ball mill to a powdered state. The experiments were performed with samples of sphagnum in the H-form, for which purpose the natural musci were pretreated in a column with diluted nitric acid in order to remove metal ions. The wash water was checked for the com255
0091-150X/02/3605-0255$27.00 2002 Plenum Publishing Corporation

Belarussian State University, Minsk, Belarus.

256
, % eC 1 450 2

A. P. Podterob et al. to four days, depending on the nature of the surfactant). Then the aqueous phases were separated, characterized by pH (EV-74 ionometr), and analyzed for cationic SASs by direct potentiometry (using ion-selective electrodes reversible with respect to the cations studied) and potentiometric titration (using a sodium tetraphenylborate solution as the titrant). The results of measurements were compared to the pH and SAS cation concentrations of the initial solutions. The experimental data were used to calculate the following values: (i) The total sorption of SAS cations [mg-eq/g] C =
2 4 6 8 10 12 14 16 18 20 DE, mV

350

250

3 4

150

50 0

V ( C 0 - C ), m

(1)

Fig. 1. Plots of the relative error of the calculated total sorption e C versus ISE potential difference DE in the initial and equilibrium solutions for various slopes of the calibration plot q and various absolute errors dE of the ISE potential measurements: q = 58 (1, 3 ) and 29 mV/pC (2, 4 ); dE = 5 (1, 2 ) and 2.5 mV (3, 4 ).

where V is the solution volume [ml], m is the sorbent mass [g], and C0 and C are the initial and final (equilibrium) solution concentrations [mg-eq/ml]. (ii) The exchange sorption of SAS cations [mg-eq/g] CH = V 10 - pH . m (2)

plete absence of divalent metal ions by the reaction with a chromogen in a buffer ammonia solution [6]. The EC values with respect to carboxy groups were determined by the barium acetate technique [7]. The humidity of sorbents was determined from the weight loss upon drying at 105C. The cationic SASs were represented by trimethyloctadecylammonium chloride, cetylpyridinium chloride, and chlorohexidine bigluconate; all compounds were of a pharmacopoeial quality. According to [3], the concentrations of SAS cations in solutions (e.g., of ethonium, decamethoxine, septonex, and N-cetylpyridinium) can be determined by a photometric technique based on the formation of a color complex with Erythrosine dye. However, this technique (as well as other chemical and microbiological methods) is rather complex and laborious, which stimulated the development of a potentiometric method [8] applicable to the analysis of cationic SASs allowed for use in medicine (cetylpyridinium chloride, chlorohexidine bigluconate, decamethoxine chloride, and ethonium chloride). Subsequent investigations [9 11] proved the potentiometric method to be a rapid and convenient means of studying the distribution of SAS cations between the aqueous phase and various objects, including natural sorption-active materials and living tissues. We have studied the sorption of cationic SASs under static conditions at 20 2C. The amount of sorption was determined by measuring a change in the external solution composition. Weighed aliquots of each sorbent were poured with equal volumes of solutions of variable concentration, stirred, and allowed to stand (with periodic stirring) until attaining the equilibrium sorption state (this stage required one

(iii) The degree of filling of the ion-exchange phase (percentage of EC) qH = CH 100. EC (3)

(iv) The limiting interphase distribution coefficient C K d = tan a = lim , C 0 C (4)

where a is the slope of the tangent to the initial potion of the sorption isotherm. (v) The degree of SAS cation isolation from solution on the initial portion of the sorption isotherm (in a single interaction cycle) q= Kd Kd + m m 100, (5)

where m is the solution mass [g]. The main errors in the calculation of these quantities are related to the error of determination of the SAS cation concentration in the aqueous solution, which, in turn, is determined by the error of measurement of the ion-selective electrode (ISE) potential. For this reason, we derived a relationship between the relative error of calculation of the total sorption (e C [%]) and the ISE potential difference DE [mV] between the initial and equilibrium solutions for various slopes q of the calibration plot and various absolute errors dE of the potential measurements:

A Potentiometric Study of the Distribution of Cationic Surfactant Antiseptics


DE q d - E 1 - 10 q DE q

257
1 b 1

10 eC =

C, mg-eq/g

C, mg-eq/g 0.6 0.5 0.4 0.3 0.2 0.1 0

100 (%).

(6)

1 - 10

Equation (6) was derived using relation (1) and the Nernst equation. Figure 1 shows the plots constructed by Eq. (6) for various values of the parameters DE, dE , and q. As can be seen, the error e C depends more strongly on the accuracy of ISE potential measurements than on the ISE sensitivity. Indeed, for the ISE sensitivities of 29 and 58 mV/pC (at the same potential count error of 2.5 mV), the values of e C corresponding to certain potential differences DE are very close (curves 3 and 4 ). In order to ensure that the relative error of determination of the total sorption would not exceed e C ~ 15%, it is necessary to select the experimental conditions so that the ISE potential difference between the initial and final solutions would be not smaller than DE ~ 15 mV (at a potential count error of 2.5 mV). In the case of potentiometric titration, the sorption is determined by the formula C = V Nt (V t0 - V t ), m V al (7)

0.6 0.5 0.4 0.3 0.2 0.1 0

2 3 4 Time, days

2 3 4 Time, days

Fig. 2. Kinetics of the total (1 ) and exchange (2 ) sorption of cetylpyridinium chloride (a) and trimethyloctadecylammonium chloride (b ) by the H-form of the green part of Sph. cuspidatum. The initial concentration of surfactant antiseptics, 5 10 4 mg-eq/ml; the solution to sorbent weight ratio, V/m = 2500.

RESULTS AND DISCUSSION As can be seen from the kinetics presented in Fig. 2, the major part of SAS cations is sorbed during the first several hours of contact between the cationic SAS and sorbent phases. However, the final equilibrium is established only on the third or even fourth day. It is natural to suggest that the initial stage corresponds to filling of readily accessible centers on the external surface and in large pores of the sorbent. The subsequent sorption is related to slow diffusion processes, namely, the internal diffusion of SAS cations toward binding sites in the sorbent and the diffusion of displaced hydrogen ions into the external medium. An analysis of the curves in Fig. 2 shows that the equilibrium level is attained by 90% one day after the contact onset. Figures 3 and 4 present the isotherms of cationic surfactant sorption in the systems studied. As can be seen, the exchange sorption (whereby the proton of a carboxy group in the sorbent is replaced by the surfactant cation) accounts for only 25 40% of the total absorbed component. Apparently, the complete replacement of protons does not take place only for sterical reasons. The ion exchange involves no more than 30 40% of carboxy groups, as follows from the exchange-sorption isotherms (Fig. 3, curve 2 ) and from the EC values (Table 1). Carboxy groups participating in the exchange are probably situated on the external surface and in large pores (capillaries) of the sorbent accessible for the SAS cations. It was established that cellulose as such does not absorb cationic SASs. This can be explained by the microcrystalline structure and the high polarity of cellulose. At the same time, cationic SASs are absorbed by the oxidized cellulose (MCC) so that a non-exchange mechanism prevails over the exchange-sorption component. Therefore, the overall process of surfactant distribution between an aqueous phase and sorbent can be described as follows. The sorption takes place at the sorbent surface and the exchange capacity is not completely realized. Initially, the exchange centers are filled and,

where V t0 and Vt are the titrant volumes required for the titration of equal volumes of the initial and final (equilibrium) solutions, Nt is the normality of the titrant solution, and Val is the volume of the titrated antiseptic solution. The limiting relative error in the calculation of sorption is given by the formula e C =| dln C | = dln(V t0 - V t ) = = dV t + dV t0 V t0 - V t = d Vt + d Vt DV
0

2d V t DV

(8)

Thus, e C is equal to the doubled error of determination of the titrant volume divided by the difference of the titrant volumes required for the titration of equal volumes of the initial and final (equilibrium) solutions. The limiting absolute error of the amount of sorption is calculated by the formula V Nt V Nt d C =| dC | = d = m V 2d V t . m V (V t0 - V t ) al al (9)

Under our experimental conditions, the limiting relative error e C according to (8) does not exceed 10%. A real uncertainty can be much lower than this limit, for example, in the case of using a microburet capillary immersed in the titrated solution.

258
C, mg-eq/g 1.2 1.0 0.8 0.6 0.4 0.2 0 1 C, mg-eq/g 1.0 0.8 0.6 0.4 0.2 0 1 C, mg-eq/g 1.4 1.2 1.0 0.8 0.6 0.4 0.2 0 b 1

A. P. Podterob et al.
C, mg-eq/g 0.6 1 2

2 1 2 3 4 C 104, mg-eq/g d 1

0.4

3 4 5 C 104, mg-eq/g c 1

2 1 2 3 4 5 C 104, mg-eq/g e 1

C, mg-eq/g 1.2 1.0 0.8 0.6 0.4 0.2 0 1 C, mg-eq/g 0.4 0.3 0.2

0.2

0
2 2 3 4 5 C 104, mg-eq/g f 1

0.75

1.50

2.25

C 10 3, mg-eq/ml

Fig. 4. Isotherms of the sorption of chlorohexidine bigluconate by sphacelated (1 ) and green (2 ) parts of Sph. cuspidatum (natural form).

C, mg-eq/g 0.4 0.3 0.2 0.1 0 2

2 4 6 C 104, mg-eq/g

0.1 0 2.5

2 5.0 C 104, mg-eq/g

Fig. 3. Isotherms of the total (1 ) and exchange (2 ) sorption: (a, b) trimethyloctadecylammonium chloride by MCC and Sph. fallax (green part, H-form), respectively; (c, d ) cetylpyridinium chloride by MCC and Sph. fallax (green part, H-form), respectively; (e, f ) cetylpyridinium chloride and trimethyloctadecylammonium chloride, respectively, by polyphepan.

as a result, the surface is rendered hydrophobic. Then, other surfactant molecules adsorb on the hydrophobic areas. The ratio of C and C H values (see Fig. 3) indicates that three to eight surfactant molecules are sorbed per exchange center, depending on the sorbent nature. The limiting interphase distribution coefficients calculated by formula (4) for water in contact with various sorbents are listed in Table 1. The high values of Kd (ranging from dozens to thousands) indicate that the sorption of

cationic SASs from aqueous solutions is thermodynamically favorable. Note also the high degree of the surfactant isolation from solutions, which range from 70.6 to 94.1% in a single interaction cycle. The total energy of a SAScation transfer from solution to sorbent includes the following components: (i) the hydrophobic interaction energy (surfactant repulsion from water molecules); (ii) the energy of electrostatic interaction between ionogenic groups of the surfactant and carboxy groups of the sorbent; and (iii) the energy of the van der Waals interaction between hydrocarbon radicals of the surfactant and the sorbent matrix. Thus, the sorption of cationic SASs by phytosorbents proceeds by a complicated mechanism predominantly on the sorbent surface. One exchange center may account for the sorption of several (three to eight) surfactant molecules. Among the phytosorbents studied (MCC, sphagnum, polyphepan), the maximum sorption activity with respect to cationic SASs was demonstrated by sphagnum. These sorbents are capable of isolating almost 90% of the surfactant cations from dilute solutions at a 1 : 2500 sorbent to solution weight ratio. Thus, properly processed sphagnum can serve as a good detoxicant capable of strongly binding and effectively eliminating from the organism cationic

TABLE 1. Limiting Distribution Coefficients (Kd) between Aqueous Solutions and Sorbents and Degrees of Isolation ( q ) of Surfactant Antiseptics from Dilute Solutions on the Linear Portion of the Sorption Isotherm
Antiseptic Sorbent and exchange capacity for carboxy groups, mg-eq/g Solution to sorbent weight ratio Kd q, %

Trimethyloctadecylammonium chloride Cetylpyridinium chloride Trimethyloctadecylammonium chloride Cetylpyridinium chloride Cetylpyridinium chloride Trimethyloctadecylammonium chloride Trimethyloctadecylammonium chloride

MCC 1.25 Sph. fallax (green part, H-form) 1.04 Polyphepan 0.13 Sph. cuspidatum (green part, natural form) 0.74

2500

1250 250

18000 15000 21000 20000 3000 3700 4000

87.8 85.7 89.4 88.9 70.6 74.7 94.1

A Potentiometric Study of the Distribution of Cationic Surfactant Antiseptics surfactant antiseptics accidentally entering into the gastrointestinal tract. The techniques and results described above can be of value for the development of sorption-based methods of eliminating toxic substances from the organism and for the creation of new enterosorbents and controlled-release antimicrobial drugs. REFERENCES
1. M. D. Mashkovskii, Drugs [in Russian], Meditsina, Moscow (1987), Vol. 2. 2. P. M. Bychkovskii, Authors Abstract of Cand. Sci. (Chem.) Thesis [in Russian], Minsk (1998). 3. I. F Zimina and V. E. Kaputskii, Kolloid. Zh., 56(4), 503 508 (1994). 4. K. I. Evstratova, L. A. Bakholdina, V. I. Kuchuk, et al., Khim.Farm., 33(8), 34 37 (1999).

259

5. Z. A. Sluka, A Concise Practical Guide in Botany: Bog Musci [in Russian], Moscow State University, Moscow (1971). 6. A. P. Kreshkov, Principles of Analytical Chemistry [in Russian], Khimiya, Moscow (1976), Vol. 2. 7. S. V. Tkachev, F. N. Kaputskii, V. E. Kaputskii, et al., Vestn. Bel. Gos. Univ., No. 2, 17 19 (1978). 8. V. V. Egorov, V. A. Repin, and V. E. Kaputskii, Zh. Anal. Khim., 51(10), 1080 1082 (1996). 9. E. M. Rakhmanko, A. P. Podterob, and V. E. Kaputskii, Abstracts of Papers. The 52nd Int. Sci.-Tech. Conf. Technical Institutes of the Belarus Republic [in Russian], Minsk (1997), Vol. 6, p. 102. 10. A. P. Podterob, V. E. Kaputskii, E. V. Zubets, and A. V. Boiko, in: Current Problems in Extraction Chemistry and Technology [in Russian], Moscow (1999), Vol. 2, p. 181. 11. A. P. Podterob, E. V. Zubets, and E. I. Yankovskii, Abstracts of Papers. The Int. Conf. Sakharov Readings 2001: Ecological Problems of the 21st Century [in Russian], Trioleta, Minsk (2001), p. 186.