Cite this article:
Jain et al. (2018). Effect of Spironolactone on the Micellar Properties of Non-Ionic Surfactant: Assessment by Conductivity and Surface Tension Methods. Journal of Ravishankar University (Part-B: Science), 31 (1), pp. 23-26.

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Monika Jain^a, S.K. Chatterjee^b, Manoj Jangde^c, Deepak Sinha^d*

^a Government Polytechnic Bhatapara (C.G.)-493118, India

^bRetd.Principal, Government M.V.P.G. College, Mahasamund (C.G.)-493554, India

^cGovernment Naveen College, Birgaon (C.G.)-492003,India

^d Government Nagarjuna Post Graduate College of Science, Raipur (C.G.)-492010, India

*Corresponding Author: drsinha333@gmail.com

[Received: 29 january 2018; Revised version: 23 March 2018; Accepted: 17 April 2018]

Abstract. An interaction of spironolactone (SPI) with octyl phenol ethoxylate (Triton-X-100 or TX-100) has been investigated by using conductometric and tensiometric measurement. The value of critical micellar concentration (CMC), degree of ionization (α) and thermodynamic parameters like standard enthalpy of micellization (ΔH°_m), standard entropy of micellization (ΔS°_m) and standard Gibb’s free energy (ΔG°_m) were determined by conductivity data. The negative value of ΔG°_m shows spontaneity in the solubilization of drug. Various interfacial parameters such as maximum surface excess concentration (Γ_max) and minimum area per molecule (A_min) was determined by surface tension measurement. All these parameters have been discussed in terms of drug-surfactant interactions. Based on the result it was found that variation in the presence of spironolactone in micellar properties of TX-100 increases with increase in concentration of drug. This study will help the pharmaceutical industries in the discovery of new drug and enhancement of their bioavailability.

Keywords: spironolactone, drug-surfactant interaction, micellar solubilization, triton-X-100.

Introduction

In pharmaceutical industries, solubility of drugs is an important factor for the early drug development. The oral bioavailability of drugs depends on several factors including aqueous solubility, drug permeability, dissociation rate, metabolism etc. The major causes of low oral bioavailability are poor solubility and low permeability. Thus, a full knowledge of the mechanism of the interactions of drugs with other foreign materials is required before the actual application in human body. This is due to the fact that drugs are always used in the presence of a variety of additives.

Spironolactone (IUPAC name- 17-Hydroxy-7-α-mercapto-3-oxo-17-α-pregn-4-ene -21- carboxylic acid-γ lactone acetate) is a potassium-sparing diuretic drug whose chemical structure is presented in Figure 2, is a non-specific aldosterone antagonist. Spironolactone is available only in the form of tablets with brand name aldactone. They have very poor aqueous solubility i.e., 0.022mg/ml.

Surfactants are amphiphilic compound having hydrophilic polar head and non-polar hydrophobic tail in a single molecule which dissolves completely at low concentrations, at least partially water soluble. Because surfactants are absorbed mainly on the surface of the solution, creating a thin monolayer, they are called surface active agents. When dissolved them, after they reach a certain value of concentration, molecules or ions of surfactants begin to associate and to organize themselves into more complex units, also called micelles. Sodium dodecyl suphate (SDS), cetyl trimethylammonium bromide (CTAB) and octyl phenol ethoxylate (Triton-X-100 or TX-100) are anionic, cationic and non-ionic surfactant respectively known to improve the dissolution rate and solubility of different drugs.

The present work concentrates on the variations occurs in the micellar and interfacial properties of TX-100 in the absence and presence of spironolactone at different temperature range. From conductometric measurement, critical micellar concentration (CMC), degree of ionization (α) and thermodynamic parameters (ΔH°_m, ΔS°_m, ΔG°_m) were calculated. Surface tension method was performed to determine CMC, maximum surface excess concentration (Γ_max) and minimum area per molecule (A_min) of all the surfactants in different concentration of spironolactone drug at room temperature. From results it was concluded that the CMC of all the surfactant decreases with increase the concentration of drug and the aqueous solubility of spironolactone increases due to interaction with surfactants.

Experimental Section

Materials

Surfactant TX-100 having purity >99% werw obtained from Molychem laboratories, Mumbai (India). Spironolactone tablets with brand name aldactone are purchased from authentic distributor. The stock solution of 0.1M TX-100 was prepared in double distilled water having specific conductivity 1-2µS and weighting were done by using an electronic balance with a precision of 0.001gm. The working solution of spironolactone drug (0.005, 0.01 and 0.05%) was prepared by 1% w/V solution of spironolactone.

Methods

Conductivity Measurements-

Conductivity measurement were performed with digital conductivity meter supplied by systronic direct reading (type 306). The conductivity cell constant was calibrated with KCl (0.001 and 0.01M) solution in appropriate concentration range. The surfactant solution was progressively added with the help of micro pipette taken in a small beaker and the conductance was measured after thorough at temperature equilibrium. The break point in the plot of specific conductivity versus the total surfactant concentration was taken as the CMC at the mole fraction.

Surface tension measurements-

Surface tension of all samples were measured by tensiometer (Jencon India) using platinum ring detachment method. Platinum ring was sterilized with flame and distilled water before each measurement. The accuracy of tensiometer was checked by measuring surface tension of pure water i.e., 72.6 mN/m. The value of surface tension was taken from average value of three measurements.

Result and discussion

Conductometric study                       

In the present work, three sets of experiment were performed with TX-100 at different concentration with SPI to observe the variation in their micellar and interfacial properties. Conductivity measurement of each sample have been carried out to determine the CMC at different temperatures (303K, 308K, and 313K). The break point in the pre-micellar and post micellar graph plotted between conductivity of solution and concentration of surfactant indicated the CMC. Degree of ionization (α) has been obtained from the ratio of slope in post micellar (S2) and pre micellar (S1) region of the graph.

It is observed in graph (1), the interaction between SPI and TX-100 shows variation in the micellar properties of pure TX-100 solution. The value of CMC of SDS decreases with increasing concentration of SPI. From the value of CMC, the thermodynamic parameters were determined. It is observed that the negative value of Gibb’s free energy shows the spontaneity of the process due to which it is also concluded that the solubility of SPI increases in micellar medium.

Table 2. Variation of CMC of TX-100 with increasing concentration of spironolactone at different temperature

Tensiometric study

Several parameters of the interfacial properties were determined by surface tension method i.e. surface excess concentration of surfactant at the air-water interface, minimum area per molecule at air-water interface, surface pressure at CMC. A linear decrease in surface tension was observed with increase in SDS concentration up to CMC. The CMC of the surfactant decreased in the presence of drug; the decrease being depended upon the concentration of spironolactone. When an increasing amount of the surfactant is added then the concentration of surfactant on water interface increases. In tensiometry, the CMC were obtained from the sharp breaks in the curve of surface tension (γ) versus surfactant concentration.

Conclusion

An increase value of CMC with increasing temperature shows that in high temperature formation of micelle decreases i.e. high temperature do not favors micellization. Presence of spironolactone decreases CMC indicates the increased solubility of spironolactone in micellar medium. But the extent of change in CMC values are very low in TX-100 as compared to ionic surfactants, which shows slightly solubility of spironolactone in non-ionic surfactant solution.

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