Introduction

Organic compounds featuring both hydrophilic (polar) and hydrophobic (non-polar) moieties within a single molecular framework are designated as surfactants1,2. These amphiphilic molecules demonstrate exceptional solubility properties and self-assembly behaviors in aqueous solutions. The formation of aggregates of surfactants called micelle which is driven by the balance of hydrophilic and hydrophobic interactions. It occurs when the concentration of a surfactant surpasses a specific threshold magnitude which is known as the critical micelle concentration (CMC)3,4. At concentrations below the CMC, surfactants remain predominantly in their monomeric state5,6,7. The interactions between surfactant molecules are significantly dependent on their surrounding microenvironment. Any changes in this environment such as the presence of additives, introduction of another surfactant or alterations in temperatures can interrupt the balance of hydrophilic and hydrophobic interactions. These changes affect various physicochemical properties such as the CMC, degree of dissociation (α), and thermodynamic parameters8,9.

Surfactants are highly effective in reducing surface and interfacial tensions and possess significant aggregation properties which make them as crucial solubilizing agents. Utilizing their aggregation properties, surfactants can encapsulate poorly soluble compounds within their cores, thereby can enhance the solubilities of respective compounds. This exceptional surface activity underscores the widespread use of surfactants in both fundamental research and various technological fields10. Many contemporary drugs face challenges to show their efficacies due to having the amphiphilic or hydrophobic properties. Formulation difficulties of drug species, their solubility in bodily fluids, interactions with cell membranes, and precise targeting are critical concerns in modern drug development11. Therefore, there is an urgent need in contemporary drug development and pharmaceutical science to discover and validate cost-effective drug formulations and delivery systems. Surfactants have gained significant attention for their potential to enhance pharmaceutical formulations and drug delivery12. Their amphiphilic nature enables them to spontaneously form micelles in aqueous solutions typically with uniform nanometer-sized distributions and often featuring a distinctive core–shell architecture13. This structure allows them to encapsulate drug molecules and thereby improving solubility as well as stability of the respective drug species. Additionally, surfactants facilitate controlled release and uptake of drugs which are crucial for developing efficient drug delivery systems14,15,16. The drug-surfactant micellar systems assist in the transportation of the drugs to the specific site, and thus reduce drugs degradation and boost bioavailability17,18,19. Statistical analyses reveal that antimicrobial agents comprise of approximately one-fourth of all prescribed pharmacological treatments and consume nearly half of the allocated pharmaceutical budget in different hospitals worldwide20.

Though surfactant micelle-based drug formulations and delivery systems offer many advantages, their development and validation necessitate a profound comprehension of the complex physicochemical properties of the respective systems. Thermodynamic study is an imperative task in elucidating the nature of molecular interactions which enhances our understanding of how drugs show activity within surfactant micellar systems21. Various chemical substances are available in our body fluids which can hamper the drug delivery processes within the body system. Therefore, it is important to explore the impact of additives in different drug-surfactant systems. The incorporation of additives such as inorganic salts into surfactant micelle systems can alter the physical properties of surfactants which can enhance the dissociation of counter ions as well as accelerate the rates of corresponding reactions. Furthermore, the presence of additives significantly influences the interactions between drugs and surfactants. Thus, it is crucial to assess the impacts of additives on drug-surfactant micelle interactions22. Habeeb et al.23 investigated the interaction of 6-Mercaptopurine (an anticancer drug) with sodium dodecyl sulfate (NaDS) micelles where they described the existence of hydrophobic interaction and hydrogen bonding. They obtained the spontaneous drug-amphiphile binding in studied circumstances. Huang et al.24 examined the interactions between NaDS and a sparingly soluble cationic drug in a dissolution medium and evaluated their impacts in vitro dissolution characteristics. Mahbub et al.25 reported the assembly nature of NaDS and cetyltrimethylammonium bromide (CTAB) in water and aq. electrolytes solutions using conductometric and molecular dynamics methods. Bhuiyan et al.26 examined the consequences of inorganic potassium salts and temperatures on the association behavior of tetradecyltrimethylammonium bromide (TTAB) in combination with bovine serum albumin (BSA). The phase behavior of four components system, polymer-H2O-surfactant-electrolyte systems has been investigated by Sheu et al.27 using a pseudo-solvent method. The voltametric study of anti-cancer drug imiquimod in the pharmaceutical formulation using NaDS has been conducted by Özok et al.28 Though many studies have been carried out previously on drug-surfactant interactions, there is a dearth of research on the interaction of antibiotic drug, ofloxacin (OFC) with anionic surfactant, sodium dodecyl sulfate (NaDS) in the presence of K-salts.

OFC (Scheme 1) is a new generation fluorinated quinolone which is commonly used as an orally administered broad-spectrum antibacterial agent found to be highly effective against most Gram-negative and Gram-positive bacteria29. While ciprofloxacin also exhibits superior in vitro antibacterial activity, OFC boasts a superior pharmacokinetic profile as it is characterized by more rapid absorption with significantly higher peak serum concentrations, as well as elevated concentrations in various tissues and body fluids30. Clinical trials have corroborated the potential of OFC for treating an inclusive variety of infections as suggested by its in vitro antibacterial and pharmacokinetic characteristics. Additionally, OFC has proven to be effective in treating various systemic infections including both acute and chronic urinary tract infections which is generally matching or surpassing the efficacy of many antibacterial drugs31. NaDS (Scheme 2) is used in various purposes where potassium is an important ion in human body fluid to keep the body balanced. Therefore, it is crucial to comprehend the mechanism behind the aggregation of NaDS and OFC in various K-salts media. This study was aimed to explore the interactions between NaDS and OFC by employing certain potassium salts (KCl, KNO3, KHSO4, K2SO4) as additives using conductivity and UV–Visible spectroscopic methods.

Scheme 1
scheme 1

Molecular model of ofloxacin (OFC).

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Scheme 2
scheme 2

Molecular representation of sodium dodecyl sulfate (NaDS).

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Interactivity between drug and surfactants molecules occur through van der Waals force, hydrophobic, electrostatic, and π-π stacking interactions32,33. These interactions depend on different factors including category and structure of the solute’s species involved34,35,36. The extents as well as strengths of drug-surfactant interactions can be assessed by determining several significant parameters like binding constants, partition constants, partition coefficients, and variation in the thermodynamics of the process37,38. To investigate the micellization characteristics of NaDS + OFC systems in different buffer (acetrate and tris buffer) solutions of different pH and the presence of K-salts media, the present study have focused on the evaluation of CMC, β values, different thermodynamic parameters of micellization (the change of free energy (\({\Delta G}_{m}^{0}\)), enthalpy (\({\Delta H}_{m}^{0}\)), entropy (\({\Delta S}_{m}^{0}\)), molar heat capacity \(({\Delta C}_{m}^{0})\), transfer parameters (\({\Delta G}_{m,tr}^{0}\), \({\Delta H}_{m,tr}^{0}\), \({\Delta S}_{m,tr}^{0}\)), and enthalpy-entropy compensation parameters (Tc and \({\Delta H}_{m}^{0,*}\))) utilizing the conductivity approach. Furthermore, binding constant (Kb), partition constant (Kc), partition coefficient (Kx), the Gibbs energy of binding (ΔGb), and Gibbs energy of partition (ΔGp) of the drug-surfactant system have been assessed accordingly through UV–Visible spectroscopic technique.

Experimental

Chemicals

All materials employed in the present study were of analytical grade and utilized without any additional modifications or purifications. Table 1 enumerates all chemicals used in the present study with detailed information on their respective suppliers, mass fraction purity, CAS numbers, and molecular weights.

Table 1 List of the chemicals and reagents utilized in the present study.
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Experimental procedures

Conductivity tool

The micelle formation of NaDS with OFC drug in aq. electrolytes environment were examined using the conductivity technique which is considered as highly reliable and widely acceptable. Conductivity measurements were meticulously performed using a Mettler Toledo conductivity meter (Model: Five Go F3, Switzerland) where the cell constant was 0.554 cm−1 used for the conductivity electrode. The conductivity meter was calibrated with a 0.01 M KCl solution to ensure the accuracy of the measurements (manufacturer-specified precision of 0.5%). It was operated within a thermostatic water bath for temperature control via water circulation. Experimental procedures commenced with the preparation of NaDS stock solutions (50 mmol kg−1) in the experimental solvent mixtures (OFC + H2O + K-salts) containing fixed concentrations of OFC (1 mmol kg−1). Each solvent mixture (20 mL) was placed in a Pyrex test tube equipped with water bath and a constant temperature was maintained during the experimental processes. After attaining the desired specific temperature, NaDS solutions were incrementally added to the respective solvent mixtures. Each addition was followed by thorough mixing with temperature equilibration. Conductivity measurements of the resulting mixtures were performed using the conductivity meter, and the data were recorded accordingly. The precision of temperatures measurements during the experimental processes was maintained within ± 0.1 K following the standard procedures as reported in literatures39,40,41. As aq. K-salts solutions were served as solvents, the magnitudes of conductivity of the solvent were subtracted from overall conductivity values to determine the contribution of NaDS to the final conductivity of the respective mixtures using the relationship of \(\kappa ={\kappa }_{overall}-{\kappa }_{solvent}\)42,43. The CMC of NaDS was determined from the plot of specific conductivity (κ) versus NaDS concentrations (CNaDS).

To investigate the effect of pH on the micellization of the respective system, the experiments were carried out in acetate buffer at pH of 2.4, 3.4, 4.4, and 5.4 (prepared from the 0.10 M acetic acid solution and 0.10 M sodium acetate solution) as well as in tris buffer at pH of 7.4 and 8.4 (prepared from 2.00 mmol kg−1 tris (hydroxymethyl) amino-methane solution and 0.20 M HCl solution) at 303.15 K.

UV–Visible spectroscopic study

The binding of drug with NaDS and partition behavior of the employed drug between the aqueous and micellar phases was studied with the assistance of differential UV–Visible spectroscopy technique following the literature described procedure37,38. A UV–Visible spectrophotometer (Shimadzu 1800 PC, Japan) was used to assess UV–Vis spectra of NaDS + OFC system, where two square top quartz cells (3.00 mL) of 1 cm path length were used to place the experimental samples. The sample holders of the spectrophotometer were connected to a tightly regulated thermostatic water bath (with an accuracy of ± 0.5 K) to assure the appropriate and constant temperature which is being maintained in the experimental samples to be placed inside the instrument during the analysis. In order to maintain the expected compositions of NaDS and a certain concentration of OFC in different media, the NaDS and OFC combined solutions were agitated for an hour in a shaking incubator. The drug solution was used as a reference for differential spectroscopic measurements where the concentration of respective drug species was kept constant (1 × 10−5 mol kg−1) and the NaDS concentrations (above 9.00 mmol kg−1) were varied in the post-micellar region. The absorption spectra were recorded at designated experimental temperature over the range of 200–800 nm. The magnitudes of absorbances measured at the maximum wavelength of drug were then used to calculate several significant parameters associated with the studied surfactant-drug system.

Results and discussion

Evaluation of micellar parameters of NaDS + OFC system in aq. K-salts media

The process of micellization in the solutions of amphiphilic materials can be comprehensively assessed via monitoring the alterations of characteristics physical properties of the respective mixtures using different techniques. However, all these properties are greatly influenced by the changes in concentrations of the respective amphiphiles solutions. In the present investigation, a conductivity measurement method was employed to scrutinize and evaluate the formation of micelles species in the mixtures of NaDS and OFC where the CMC values were determined from the plot of κ versus concentrations of amphiphiles solutions. Figure 1 graphically represents the dependency of κ values on the NaDS concentrations of NaDS + OFC mixtures in aq. K2SO4 medium at a temperature of 303.15 K. In each of experiments conducted in this study, a singular inflection point was perceived for the assembly of NaDS with OFC drug in aqueous solutions of K-salts. Analysis of the data obtained from the plot of κ against amphiphile concentrations (Fig. 1) reveals that the slope of the corresponding straight-line equation in the post-micellar phase (S2) was shallower in comparison to the respective slope observed in the case of pre-micellar phase (S1). This difference in the magnitudes of slopes might be appeared due to the creation of larger aggregates as characterized by reduced mobility of components in a sharp contrast to the swift movement of individual ions with smaller in sizes.

Fig. 1
figure 1

The variation of κ with the concentrations of NaDS (CNaDS) within the NaDS + (1.004 mmol kg−1) OFC system in aq. K2SO4 (5.013 mmol kg−1) solution at 303.15 K. The error in CMC =  ± 3%.

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The appearances of these distinctive slopes (S1 and S2) serve as the basis for the calculation of the extent of counter-ion dissociation as denoted by α which is obtained from the equation, \(\alpha ={S}_{2}/{S}_{1}\)44,45. This parameter α holds significant implications in characterizing surfactant micelles as well as it greatly influences several critical factors such as micellar stability, structural transitions (spherical to rod-shaped micelles), as well as viscoelastic properties of the respective surfactant-drug mixtures46,47. Additionally, the parameter β explains the extent of counterion binding which was calculated using the relation \(\beta =1-\alpha\)48,49. The magnitudes of α also profoundly explains the reaction rates of organic compounds within micellar environments, as well as govern the degree of different intricate thermodynamic parameters associated with micellization process50.

Effect of K-salts on the assembly process

In our previous study, we explored the molecular mechanism behind the interactions between NaDS and OFC species and the results were reported in literature. The CMC of NaDS was observed to be increased with the elevation of the concentrations of OFC from 0.55 to 11 mmol kg−1 in aqueous medium51. The –COOH group within the structure of OFC forms H-bond with water molecules gathered around the head group of NaDS keeping hydrophobic part of OFC inward of the micelle species which resulted the decrease in the degree of counterion binding. This reduction in the counterion binding in the presence of OFC yielded the higher CMC of NaDS solutions. The development of partial negative charge on the oxygen atom of –COOH group might increase the electrostatic repulsion among the negatively charged head group (–SO42−) of NaDS which also might inhibit the formation of micelle species and thus increased the CMC of the respective system. As the activity of drug species greatly depend on the CMC of the respective surfactant used as excipient during the formulation (optimum activity is observed at CMC while it is being lowered at any concentration below and above the CMC)12, the precise estimation of CMC and other associative behaviors in the presence of different constitutes of body fluids are very important from the applications view point of drug compounds. The dose rate of ofloxacin can be varied (10–15 mg/kg/day or maximum 800 mg/day) depending on the human age and body weight30. In the current investigation, a fixed concentration of OFC drug (1.00 mmol kg−1) was used to examine the impacts of different anions and compositions of K-salts on the associative behavior of NaDS + OFC mixtures. Different solutions of KCl, KNO3, KHSO4, and K2SO4 have been employed as electrolytes media to examine their impacts on the micellization processes. The usual concentration of K+ ion in the extracellular fluid (plasma) is 3–5 mmol/L52. The behavior of drug (release and absorption) in the blood stream depends on the level of electrolytes species in the blood stream. To gain insight on the behavior of drugs in the presence of K+ ion, we selected a range of concentrations of K-salts solutions which were covered the normal plasma concentration for K+ ion. Therefore, in the present investigation, the concentrations of each K-salt were selected between 0.5 and 10 mmol kg−1. The CMC values for the NaDS + OFC mixed system in aq. electrolytes media was found to be lower in magnitudes than those observed in the pure aqueous medium51. The magnitudes of CMC and the respective β values for the NaDS + OFC mixtures showed a gradual reduction as well as the augmentation respectively with rising of the concentrations of corresponding electrolytes solutions (Fig. 2 and Table 2).

Fig. 2
figure 2

Variation of CMC in the NaDS + (1.001 mmol kg−1) OFC combination with the concentrations of different K-salts media (CK-salt) at 303.15 K. The error in CMC =  ± 3%.

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Table 2 The magnitudes of different micellar variables (CMC, α, and β) for the NaDS + OFC system in the attendance of K-salts at 303.15 K.
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The decrease in surface charge density of the micelle species causes the reduction in the columbic repulsions between the head groups of the corresponding constituents which eventually results the reduction of CMC in aqueous electrolytes solution53. The mechanism of interactions of the ions generated from salts with the micelles species was also reported in literatures54,55. It has been found that the electrical double-layer could be compressed due to the declining of interactions between the potassium ions and micelles species in the manifestation of greater contents of salts54. According to the study conducted by Jakubowska55, both Na+ (from NaDS) and K+ (from K-salts) ions might have bound to the surfaces of NaDS micelles species. Mahbub et al.25 have reported the lowering of CMC values for the NaDS/NaDS + CTAB mixed systems in various electrolytes (KCl, NaCl, NH4Cl) media compared to those observed in the aqueous medium. Bhuiyan et al.26 described the interactions of BSA with TTAB where the CMC values experienced a noticeable diminution with the attendance of KCl, K2SO4, and K3PO4 solutions. Ahsan et al.56 reported that the extents of CMC which were decreased with growing of NaCl concentrations, then reached to a minimum, and consequently the respective CMC values were increased with further increments of NaCl concentrations in the case of lomefloxacin hydrochloride (LMFH) + NaDS systems in aq. NaCl medium. Conversely, the corresponding CMC values of the surfactant-drug system exhibited the opposite trend in Na2SO4 and Na3PO4 media. The similar findings of CMC were also noticed for the assembly of NaDS with levofloxacin hemihydrate (LFH)21. Woolfrey et al.57 have reported the reduction in the CMC values of NaDS in the incidence of NaCl solution as determined by surface tension method. Kumar and Kaur58 described a decline in the CMC of the mixtures comprising of NaDS and promazine hydrochloride (PMT) drugs as measured by conductivity technique when NaCl was present in the studied system. The outcomes of the lowering in the magnitudes of CMC within the mixtures of NaDS with OFC drug in the presence of potassium salts media showed that the introduction of salts solution is highly beneficial to the applications of NaDS in different pharmaceutical formulations.

Effect of temperature

The specific conductivities varied significantly with the changes in temperatures of experimental system. Figure 3 discloses the changes in the conductivities of NaDS + OFC mixtures with KCl solutions at different experimental temperatures. As the temperature rises, an increase in the conductivity values of the respective system was realized. The observed CMC and β values for the NaDS + OFC mixtures in different electrolytes solutions at different experimental temperatures are shown in Table 3 and Fig. 4.

Fig. 3
figure 3

Plots of κ versus [NaDS] for the NaDS + (1.001 mmol kg−1) OFC system in aq. KCl solutions at different experimental temperatures.

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Table 3 The physcial parameters of NaDS and 1.001 mmol kg−1 OFC mixture in incidence of different K-salts at working temperatures.
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Fig. 4
figure 4

The dependency of CMC on the changes in temperatures (T) for the association of NaDS + OFC drug in aqueous solutions of different K-salts.

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In the present investigation, the magnitudes of CMC in all potassium-salts media were found to be increased with the enhancement of experimental temperatures (Table 3). The correlation between CMC of surfactant and temperatures can be rationalized by hydrophobic and hydrophilic hydrations59. However, a similar study conducted by Tanford60 and reported two opposing thermally controlled phenomena in surfactant-drug mixtures to explain the impact of temperatures on CMC. There is an increase in hydrophobicity which results from heightened dehydration of polar head groups, while the second factor explains the disruption of micelle species due to the increase in thermal solubility of amphiphiles with rising of temperatures within the corresponding systems. In the case of ionic and non-ionic surfactants, several other factors are also involved which have been documented in the literatures61,62,63. Typically, the degree of CMC associated with ionic surfactants decreases at lower temperatures whereas the extent of corresponding CMC increases at higher experimental temperatures. There is a consistent upward trend in CMC was also realized for ionic surfactants with increasing in temperatures of the surfactant-drug systems63,64,65. The extents of CMC found from the present investigation showed a strong consistency with the data reported previously in literatures from similar studies63,64,65. For the assembly of NaDS with pepsin protein in aqueous solution of sodium salts, the nonlinear increase of CMC with increasing temperature was recently reported by our group8. In a recent work performed by our group, the U-shaped CMC versus T plots were achieved for the association of similar surfactant-lithium dodecyl sulfate with propranolol drug in the presence of potassium salts42. The impact of temperature on the CMC can be explained by the interplay of hydrophilic and hydrophobic hydrations. Though molecular structures of amphiphilic compounds have the same hydrophobic chains, the unique interactions caused by their head group with water molecules could make differences in their CMC values with the changes in temperatures. The temperature-induced changes in CMC could be rationalized by two opposing thermally regulated phenomena: (1) increasing of dehydration within the head group which rises the molecular hydrophobicity, and (2) rapturing of micelle species which occurs due to the molecular thermal solubility. The interactions between these factors are greatly dependent on surfactant solubility, fluctuations of experimental temperatures, and the relative strengths of these effects can determine whether the corresponding CMC values will be increased or decreased60. In the case of ionic surfactants, the extent of CMC initially decreases at lower temperatures whereas the corresponding CMC values subsequently increases at higher experimental temperatures. Conversely, the magnitude of CMC experiences a reduction for non-ionic amphiphiles with rising of experimental temperatures59. In the NaDS micellization process, an elevated temperature could enhance the kinetic energy of constituents which might cause the disintegration of the ordered structure of micelles. Consequently, the decrease in aggregation number might also contribute to the elevation of CMC values. The relationship of CMC with the changes in temperatures is explicable by considering the alterations in hydration for both monomeric and micellized states of the amphiphile in pure and mixed systems. In the monomeric phase, both hydrophobic and hydrophilic hydrations are feasible whereas the hydrophobic hydration becomes absent following the surfactant micellization. Both hydrations’ processes might be diminished with increasing in experimental temperatures. The reduction in hydrophilic hydration triggers earlier micellization leading to a decrease in CMC values. On the other hand, the decline in hydrophobic dehydration around the hydrophobic segments of the surfactant retards micellization process resulting in an elevation of CMC values66,67. The reduction in water organization surrounding the nonpolar alkyl chain segment of the amphiphile structure at elevated temperatures could be responsible for the rise in the magnitudes of CMC and thus impeding the usual micellization process68,69. Bhuiyan et al.26 reported the micellization behaviors of TTAB + BSA mixtures where the magnitudes of CMC exhibited a gradual increase with the elevation of temperatures in various aq. electrolyte (KCl, K2SO4, and K3PO4) solutions. The β values showed a downward trend with an increase in temperatures in all solvents media which further rationalized the augmentation in CMC values at elevated temperatures. The appearances of higher magnitudes of β are indicative of the enhanced stability in the fabricated micelle species70.

Effect of pH on the micellization of NaDS with OFC drug

To better understand the mechanism of micellization of NaDS + OFC drug mixture, different buffer solutions of variable pH were utilized. Both acidic buffer (acetate buffer) with variable pH of 2.4, 3.4, 4.4, and 5.4 and basic buffer (tris buffer) with pH of 7.4, and 8.4 were used to conduct the respective experiments at different pH and the conductivities of the resulting mixtures were measured accordingly. The κ profile obtained with the enhancement of concentrations in NaDS solutions has been demonstrated in Fig. 5. In all cases one CMC values was attained. The lower CMC was obtained at lower pH values (in acetate buffer solutions) in comparison to unbuffered water medium while the CMC values showed an increase with the increase of pH values (Table 4). At pH of 7.4 and 8.4 (Tris buffer), the CMC values became higher in magnitudes compared to unbuffered water medium.

Fig. 5
figure 5

The changes of κ with the variation in concentrations of NaDS (CNaDS) in the NaDS + (1.001 mmol kg−1) OFC system in acetate buffer solution of pH 3.4 at 303.15 K. The error in CMC =  ± 3%.

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Table 4 The magnitudes of CMC of NaDS with 1.001 mmol kg−1 OFC drug in different buffer solutions of variable pH at 303.15 K.
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Fuguet et al.71 observed the decrease of CMC of NaDS (from 6.09 to 1.99 mM) with increasing in concentrations of electrolytes from 5 to 50 mM in phosphate buffer solution of pH 7.0 at 298.15 K where they observed the CMC of 1.99 in 0.05 M phosphate buffer (pH 7.0) using the conductivity method. Gupta et al.72 reported the lowering of CMC value of NaDS in 0.2 M Tris buffer solution in comparison to aqueous medium where they obtained the higher CMC of the identical amphiphile in 0.5 and 1.0 M Tris buffer solutions. They concluded that the electrostatic interaction between positively charged tris and negatively charged amphiphile caused the promotion of NaDS micellization whereas the increase of CMC in tris buffer solution having higher concentration had occurred due to the increase in hydrophilic character of the medium73.

Thermodynamics of micellization

The molecular interactions between drugs and surfactants intricately dictate the rate of drug delivery and release. Different thermodynamic parameters such as Gibbs free energy (\({\Delta G}_{m}^{0}\)), the enthalpy (\({\Delta H}_{m}^{0}\)), and the entropy (\({\Delta S}_{m}^{0}\)) changes for the assembly of NaDS with OFC drug in aq. potassium salts were calculated using the following Eqs. (1)–(5)74,75.

$${\Delta G}_{m}^{0}=\left(1+\beta \right)RTln{X}_{CMC}$$
(1)
$${\Delta H}_{m}^{0}=-\left(1+\beta \right){RT}^{2}\left({lnX}_{CMC}/\partial T\right)$$
(2)

In the Eqs. (1) and (2), XCMC, R and T signify the mole fraction of CMC, the gas constant, and the experimental temperature respectively. Figure 6 shows the plot of \(ln{X}_{CMC}\) versus T obtained for the association of amphiphiles based on the Eq. (3).

Fig. 6
figure 6

The plot of \({lnX}_{CMC}\) versus T (second-order polynomial fitting) for the NaDS + (1.001 mmol kg−1) OFC system in aq. KHSO4 (4.999 mmol kg−1) medium.

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$$ln{X}_{CMC}=A+BT +{CT}^{2}$$
(3)

The magnitudes of regression constants A, B, and C were determined by the application of a second-order polynomial fitting to Eq. (3) (Table 5). Then, the \({\Delta H}_{m}^{0}\) and \({\Delta S}_{m}^{0}\) values were calculated by utilizing the Eqs. (4) and (5) respectively.

Table 5 The fitting parameters of the studied surfactant-drug system obtained from second-order polynomial fitting to the plot of \({lnX}_{CMC}\) versus T using Eq. (3).
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$${\Delta H}_{m}^{0}=-\left(1+\beta \right)R{T}^{2} \left(\text{B }+2\text{CT}\right)$$
(4)
$${\Delta S}_{m}^{0}=({\Delta H}_{m}^{0}-{\Delta G}_{m}^{0})/T$$
(5)

Table 6 provides comprehensive magnitudes of \({\Delta G}_{m}^{0}\), \({\Delta H}_{m}^{0}\), and \({\Delta S}_{m}^{0}\) for the NaDS + OFC mixtures in different aq. potassium salts media. \({\Delta G}_{m}^{0}\) values for the studied system were found consistently negative across all the experimental media. The results suggest that the aggregation processes of NaDS + OFC mixtures in K-salts media were thermodynamically favorable.

Table 6 The magnitudes of \({\Delta G}_{m}^{0}\), \({\Delta H}_{m}^{0}\), \({\Delta S}_{m}^{0}\), and \({\Delta C}_{m}^{0}\) for the association of NaDS + (1.001 mmol kg−1) OFC mixtures in the attendance of different K-salts.
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The appearances of negative \({\Delta G}_{m}^{0}\) signify that the formation of micelles is spontaneous indicating a usual tendency to amphiphile molecules to be associated and established stable structures in the respective media. This thermodynamic favorability underscores the likelihood and intrinsic spontaneity of the association processes which occurred in the NaDS + OFC mixtures. In all experimental media, the negative magnitudes of \({\Delta G}_{m}^{0}\) exhibited an upward trend with the enhancement of temperatures. \({\Delta H}_{m}^{0}\) values for the NaDS + OFC system in all potassium salts solutions showed a consistent positive magnitude at lower temperatures whereas the negative \({\Delta H}_{m}^{0}\) were observed at elevated temperatures which indicated that the occurrence of micellization was shifted from endothermic to exothermic process with rising of experimental temperatures. Moreover, the \(-{\Delta H}_{m}^{0}\) values observed in all experimental media display an increasing in negative magnitudes with the elevation of thermal energy. This pattern of changing \({\Delta H}_{m}^{0}\) implies that the micellization process releases more heat energy at upper temperatures. \({\Delta S}_{m}^{0}\) values of NaDS + OFC mixtures were found as positive in all solvents even with the augmentation of experimental temperatures. Additionally, the magnitudes of \({\Delta S}_{m}^{0}\) followed a downward pattern in all cases with rising of temperatures which confirmed more ordered structural arrangement as adopted by NaDS molecules in electrolytes. At lower temperatures, both \({\Delta H}_{m}^{0}\) and \({\Delta S}_{m}^{0}\) values were observed to be positive, indicating that the micellization progression was dominated by entropy. On the other hand, at 308.15 K or upper temperatures, the respective process was predominantly governed by enthalpy changes. The results of \({\Delta H}_{m}^{0}\) and \({\Delta S}_{m}^{0}\) analysis connote that OFC might interact with NaDS by electrostatic, H-bonding, ion–dipole, and hydrophobic forces. The appearance of negative \({\Delta H}_{m}^{0}\) values implied the incidence of London-Dispersion force between the OFC drug and NaDS species where the robust hydrophilic hydration might cause the rupturing of H2O structure around the nonpolar tails of the amphiphiles49,76. These findings also revealed the presence of hydrophobic interactions between the nonpolar aromatic and aliphatic moieties of OFC drug and nonpolar tail of NaDS species within the respective mixtures in aq. potassium salts media77. A schematic diagram is provided in Fig. 7 to show the plausible interaction forces between OFC drug and NaDS in aqueous solution of KCl. Negative \({\Delta H}_{m}^{0}\) as well as \(+{\Delta S}_{m}^{0}\) were observed for the aggregation of NaDS in hexanediol + H2O mixed solution as reported from the study conducted by microcalorimetric method78. Mahbub et al.25 have found the positive magnitudes of both \({\Delta H}_{m}^{0}\) and \({\Delta S}_{m}^{0}\) for NaDS as well as NaDS + CTAB mixtures in the presence of KCl and NaCl solutions within the temperature changes between 298.15 K and 318.15 K. Rather et al.79 reported \({-\Delta H}_{m}^{0}\) and \(+{\Delta S}_{m}^{0}\) values for the NaDS + PVA mixtures in aq. NaCl medium. Makowska et al.80 also noted the negative magnitudes of \({\Delta H}_{m}^{0}\) (exothermic process) for the exothermic micellization of NaDS in different buffer solutions as studied by isothermal titration calorimetry (ITC).

Fig. 7
figure 7

A diagram showing the probable interaction forces between OFC drug and NaDS in aqueous solution of KCl.

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The molar heat capacity (\({\Delta C}_{m}^{0}\)) can provide significant information on the micellar representation of surfactants as well as the binding characteristics of proteins/drugs with amphiphiles. The magnitude of \({\Delta C}_{m}^{0}\) was determined from the slope of the straight-line (Eq. 6) obtained from the plot of \({\Delta H}_{m}^{0}\) against T (Fig. 8)26,51.

Fig. 8
figure 8

The temperature dependency of \({\Delta H}_{m}^{0}\) values for the NaDS + (1.003 mmol kg−1) OFC mixtures in aq. KNO3 (5.001 mmol kg−1) solution.

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$${\Delta C}_{m}^{0}={(\partial {H}_{m}^{0}/\partial T)}_{P}$$
(6)

The \({\Delta C}_{m}^{0}\) values for the micellization of NaDS + OFC in aq. K-salts solutions have been listed in Table 6. The magnitudes of \({\Delta C}_{m}^{0}\) determined in the present study were consistently found to be negative across all temperatures and additives media. These results suggested that the aggregated species has experienced a diminishing of heat capacity in comparison to the combined heat capacities of the respective unaggregated components. The alterations in the \({\Delta C}_{m}^{0}\) values indicated a reorganization of the structural configuration of NaDS micelle species which was facilitated by OFC in the presence of salt-containing media. These observations coupled with theoretical understanding of the respective surfactant-drug system implied that the change in \({\Delta C}_{m}^{0}\) had appeared from the variations in the degree of surface hydration in the cases of free and aggregated molecules51,81. The magnitudes of \({\Delta C}_{m}^{0}\) obtained from the present investigation in the designated surfactant-drug system were very close to the data reported previously in literature from the similar studies conducted by other research groups26,82.

Thermodynamics of transfer

The standard Gibbs free energy (\({\Delta G}_{m,tr}^{0}\)), enthalpy (\({\Delta H}_{m,tr}^{0}\)), and entropy of transfer (\({\Delta S}_{m,tr}^{0}\)) were calculated using the following Eqs. (7–9)56,82,83.

$$\Delta {G}_{m,tr}^{0}=\Delta {G}_{m}^{0} \left(aq. \,additives\right)-\Delta {G}_{m}^{0} \left({H}_{2}O\right)$$
(7)
$$\Delta {H}_{m,tr}^{0}=\Delta {H}_{m}^{0} (aq. \,additives)-\Delta {H}_{m}^{0} \left({H}_{2}O\right)$$
(8)
$$\Delta {S}_{m,tr}^{0}=\Delta {S}_{m}^{0} (aq.\, additives)-\Delta {S}_{m}^{0} \left({H}_{2}O\right)$$
(9)

The thermodynamic behaviors for the association of NaDS + OFC mixtures in aqueous system, were documented in our previous publication. These data have been employed in the present study to calculate various transfer parameters associated with designated surfactant-drug system51. The magnitudes of \({\Delta G}_{m,tr}^{0}\), \({\Delta H}_{m,tr}^{0}\), and \({\Delta S}_{m,tr}^{0}\) determined for the micellization of NaDS in aq. K-salts media facilitated by OFC drug have been outlined in the Table 7. All \({\Delta G}_{m,tr}^{0}\) values in all the investigated conditions were found to be negative irrespective of experimental conditions and additives media. The appearances of negative magnitudes of \({\Delta G}_{m,tr}^{0}\) indicate a rapid, spontaneous aggregation of micelle species and manifest that the transfer process of surfactant micelles from aqueous medium to electrolyte solution is thermodynamically favorable. The \({\Delta G}_{m,tr}^{0}\) values for the NaDS + CLM (cephalexin monohydrate) mixed system were observed as negative in aq. NaCl solution (≤ 10 mmol kg–1) as reported in literature84.

Table 7 The magnitudes of \({\Delta G}_{m,tr}^{0}\), \({\Delta H}_{m,tr}^{0}\), and \({\Delta S}_{m,tr}^{0}\) for the NaDS + (1.001 mmol kg–1) OFC mixed system in various aq. K-salts media.
Full size table

In the present study, both \({\Delta H}_{m,tr}^{0}\) and \({\Delta S}_{m,tr}^{0}\) were obtained positive at lower experimental temperatures whereas these values were found to be negative at upsurged temperatures. This negative \({\Delta H}_{m,tr}^{0}\) indicated that movement of the hydrophilic parts of the surfactant species from water to salts solutions was exothermic whereas the corresponding transferring of hydrophobic parts had occurred in endothermic ways85,86. For the NaDS + CPFH (ciprofloxacin hydrochloride) mixtures in inorganic Na-salts, the executed values of \({\Delta G}_{m,tr}^{0}\), \({\Delta H}_{m,tr}^{0}\), and \({\Delta S}_{m,tr}^{0}\) were observed to be both negative and positive in magnitudes70. The \({\Delta H}_{m,tr}^{0}\) values for the micellization of pure TTAB in appearance of NaCl solutions were observed to be negative as reported in literature from the study conducted previously within the similar temperature range82. In the case of NaDS + LMFH mixtures, the \({\Delta H}_{m,tr}^{0}\), and \({\Delta S}_{m,tr}^{0}\) values were observed as both positive and negative in NaCl/Na2SO4 environment56.

Enthalpy-entropy compensation of NaDS + OFC mixed system in aq. K-salts

The plot of \({\Delta H}_{m}^{0}\) against \({\Delta S}_{m}^{0}\) for the association of the NaDS + OFC mixtures yielded a straight line with reasonable R2 values as represented in Fig. 9 which suggested a strong linear relationship between \({\Delta H}_{m}^{0}\) and \({\Delta S}_{m}^{0}\). Enthalpy–entropy compensation parameters such as intrinsic enthalpy gain \({(\Delta H}_{m}^{0,*})\) and compensation temperature \({(T}_{c})\) were consequently assessed in the studied drug-surfactant system in aq. K-salts media by using the following Eq. (10)87,88,89,90,91,92,93.

Fig. 9
figure 9

The plot of \({\Delta H}_{m}^{0}\) versus \({\Delta S}_{m}^{0}\) for the aggregation of NaDS with 1.001 mmol kg−1 OFC in aq. KCl (5.011 mmol kg−1) solution.

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$${\Delta H}_{m }^{0}={\Delta H}_{m}^{0,*} +{T}_{c}{\Delta S}_{m}^{0}$$
(10)

The enthalpy-entropy compensation of the NaDS and OFC mixed system has been determined to understand the interactions of solute–solvent as well as solute–solute interactions90,92. The enthalpy–entropy compensation parameters, demonstrated a significant correlation with each other, obtained from the NaDS + OFC system in aq. K-salts media are shown in Table 8. The \({T}_{c}\) values serve as pivotal indicators of the solvation dynamics exhibited by drug + surfactant mixtures in diverse solvent environments. Specifically, \({T}_{c}\) values within the range of 270–350 K have been leveraged to ascertain the water content in protein reactions94. The computed \({T}_{c}\) values computed in the designated surfactant-drug system during the present study were found to be within the range of 274.2–279.2 K, which were strongly correlated to the data reported previously in literature94. The assessed \({\Delta H}_{m}^{0,*}\) values were observed as negative. The substantial negative magnitudes of \({\Delta H}_{m}^{0,*}\) indicated that the micellization of NaDS was significantly accelerated even at \({\Delta S}_{m}^{0}=0\). The pronounced upsurge in negative \({\Delta H}_{m}^{0,*}\) demonstrated a robust stability of the micelles formed in K2SO4 medium95,96. The magnitudes of \({T}_{c}\) and \({\Delta H}_{m}^{0,*}\) determined in the NaDS + OFC system with aq. potassium salts media were found to be highly consistent with the literature value of corresponding amphiphile (NaDS) as well as the data reported from several identical studies conducted previously by other research groups56,70.

Table 8 The magnitudes of intrinsic enthalpy gain (\({\Delta H}_{m}^{0,*}\)) and compensation temperature (\({T}_{c}\)) for the NaDS + (1.006 mmol kg−1) OFC mixed system in different electrolytes media.
Full size table

UV–Visible spectroscopic study of NaDS + OFC system in aqueous and aq. KCl solutions

The UV–Visible absorption spectra of pure OFC drug and its mixture with 10.0 mmol kg−1 NaDS in aq. KCl solution at 298.15 K has been depicted in Fig. 10. The maximum wavelength \(({\lambda }_{max})\) of 1 × 10–5 mol kg−1 OFC drug in aq. KCl solution was found 290 nm. This \({\lambda }_{max}\) value was continuously shifted up to 299 nm (red shift) due to the augmentation of the concentrations of NaDS solutions which indicated the existence of noteworthy interactions between OFC drug and NaDS micelle species.

Fig. 10
figure 10

The UV–Visible spectra (Absorbance versus wavelength (nm) plots) for 1 × 10−5 mol kg−1 OFC in absence and presence of 10 mmol kg−1 NaDS in aq. KCl solution at 298.15 K.

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Determination of partition constant, partition coefficient, and binding constant for the NaDS + OFC system

The partitioning constant is used to quantify the extents of drug solubilization. The greater the magnitudes of partitioning constant, the higher the drug concentrations within the micelle species compared to those present in the bulk aqueous phase. The equilibrium constant for the reaction of surfactants with drugs or dyes can alternatively be referred to as the partitioning constant17,37. The degree of interaction between the drug and surfactant micelles is quantified by determining the binding constant (Kb) and the micelle-water partition coefficient (Kx) at various temperatures97. The differential absorption data were used to determine the binding and partition characteristics of single and mixed micellar media in the presence of drug species37,98,99,100. Equations (11) to (16) show the mathematical expressions needed to determine these parameters. The partitioning parameter was determined using the following Kawamura equation (Eq. 11)101,102,103.

$$\frac{1}{\Delta A}= \frac{1}{{K}_{c}{\Delta {A}_{\infty }({C}_{d}+C}_{s}^{{m}_{0}})}+\frac{1}{\Delta {A}_{\infty }}$$
(11)

The differential absorbance values at normal and infinite concentrations are denoted by \(\Delta A\) and \(\Delta {A}_{\infty }\) respectively. \({C}_{d}\) represents the concentration of drug and \({C}_{s}^{{m}_{0}}\) indicates the analytical concentration of the surfactant used in the experimental mixtures. The \({C}_{s}^{{m}_{0}}\) can be calculated using the Eq. (12)102,104.

$${C}_{s}^{{m}_{0}}= {C}_{s}-CM{C}_{0}$$
(12)

where \({C}_{s}\) is the concentration of surfactant and CMC0 is the CMC of surfactant in absence of additives. The partition constant (\({K}_{c}\)) was calculated using the above mathematical expression. The plot of \(1/\Delta A\) vs. \({1/({C}_{d}+C}_{s}^{{m}_{0}})\) yielded a straight-line equation from which the slope was divided by the intercept to obtain the partition constant (\({K}_{c}\)) (Fig. 11b).

Fig. 11
figure 11

Plot for calculation of (a) binding constant (Kb) and (b) partition constant (Kc) for NaDS + (1 × 10–5 mol kg−1) OFC system in water at 298.15 K.

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The value of \({K}_{c}\) was utilized to calculate the partition coefficient (\({K}_{x}\)) using the Eq. (13)102,105.

$${K}_{x}= {K}_{c}{n}_{w}$$
(13)

Here, \({n}_{w}\) represents the number of moles of water 55.55 mol kg−1. The magnitudes of Kc and Kx obtained for the NaDS + OFC system in aqueous medium and aq. salt medium are presented in the Table 9.

Table 9 The magnitudes of binding constant (Kb), partition constant (Kc), partition coefficient (Kx), Gibbs energy of binding (ΔGb), and Gibbs energy of partition (ΔGp) for the mixture of NaDS and 1 × 10–5 mol kg−1 OFC at \({\lambda }_{max}\) of 299 nm.
Full size table

The significant higher values of Kx demonstrated the noteworthy transfer of OFC drug from water to the NaDS micellar phase. The values of Kc and Kx were found to be reduced in the presence of KCl which reveals that drug transfer from aqueous phase to NaDS micellar phase is reduced in presence of KCl. The values of Kx are lower in KCl solutions than in water media indicate that the OFC is partitioned in NaDS micelle to lesser extent in KCl solution. Toader et al.97 reported the Kx values for the NaDS micelle-water in anticancer drug, quinizarin solutions are 3.44 × 105 M−1 at 293.15 K and 4.74 × 105 M−1 at 303.15 K. Enache and Toader106 obtained the value of Kx is 2.47 × 104 M−1 for the interaction of mitoxantrone with NaDS micelles at pH 7.4. Hanif et al.107 noted the value of Kx for the partitioning of benzothiophene (BNP) with NaDS is 1.03 × 105 M−1 using UV–Visible spectroscopic study. The Kx value was found 4.5 × 104 M−1 for reactive yellow 86 (RY86) /NaDS system108. Banipal et al.37 calculated the Kc value for the system of CPFH and NaDS is 4.29 × 103 M−1 in water medium at 298.15 K. Again, the higher values of Kc and Kx at higher temperature signify that drug transfer from aqueous phase to NaDS micellar phase accelerate at higher temperature. Therefore, the values of Kx obtained in the present study shows the decent agreement with the literature values37,97,106,107,108.

The binding constant \(({K}_{b})\) was calculated using the modified Benesi–Hildebrand expression as given below (Eq. 14)109.

$$\frac{{dC}_{d}}{\Delta A}= \frac{1}{{K}_{b}{\Delta \varepsilon C}_{s}^{{m}_{0}}}+\frac{1}{\Delta \varepsilon }$$
(14)

where “\(d\)” is the optical path length and “\(\Delta \varepsilon\)” denotes the difference between the absorption coefficients. The plot of \(\frac{{dC}_{d}}{\Delta A}\) versus inverse of \({C}_{s}^{{m}_{0}}\) was used to calculate the magnitudes of \({K}_{b}\) (Fig. 11a)110.

The assessed values of \({K}_{b}\) are shown in Table 9. The values of \({K}_{b}\) were found to be reduced in the presence of KCl due to diminished hydrophobic interactions between OFC and NaDS in the presence of KCl, while the \({K}_{b}\) values enhance with the rise of temperature in both aqueous and aq. KCl medium. Erdinch et al.111 found the Kb values for the binding of NaDS with 4.0 × 10–5 M antitumoural drug, Epirubicin HCl are 8.55 × 102 M−1 in water and 8.01 × 102 M−1 in 0.5% (w/v) NaCl solution at 298 K, which is lower than the aqueous medium. For the binding of diclofenac sodium (DCF), a nonsteroidal anti-inflammatory drug, to hexadecyltrimethylammonium bromide (HTAB) in the presence of 0.05 M NaCl compared to water medium, calorimetric measurements revealed a reduction in Kb values from 7.40 × 103 to 3.20 × 103 M−1, while it showed a change from 4.90 × 103 to 4.70 × 103 M−1 by spectroscopic determination98. But, Banipal et al.37 and Gawandi et al.112 reported in their study that the presence of NaCl increases the binding constant for the CPFH/NaDS and Cresyl Violet (dye)/NaDS system, respectively. The Kb value for the interaction of quinizarin with NaDS was observed to be higher 3.3 × 103 M−1 at 303.15 K than 2.5 × 103 M−1 at 293.15 K97.

Thermodynamics for the binding and partition of NaDS + OFC system

The following equations were used to determine the thermodynamic parameters (Gibbs energy of binding (∆\({G}_{b}\)) and Gibbs energy of partition (∆\({G}_{p}\))) based on the values of the binding constant and partition coefficient113,114.

$${\Delta {G}_{b} =- RT\, lnK}_{b}$$
(15)
$${\Delta {G}_{p} =- RT\, lnK}_{x}$$
(16)

The results of Gibbs energy of binding (∆\({G}_{b}\)) and Gibbs energy of partition (∆\({G}_{p}\)) obtained for the NaDS + OFC mixed system in aq. salts media have been presented in Table 9. The values of ∆\({G}_{b}\) and ∆\({G}_{p}\) were found to be negative both in aqueous and aq. KCl medium which signify the spontaneous binding and partitioning of the studied system as well as the stability of the system115. The lessening of negative values of ∆\({G}_{b}\) and ∆\({G}_{p}\) in the presence of KCl signify reduced spontaneity in the presence of KCl. Besides, the values of ∆\({G}_{b}\) and ∆\({G}_{p}\) become more negative with the increase in temperature for both binding and partition processes revealing that both processes are more spontaneous at elevated temperature. The computed values of \({K}_{b}\), Kc, Kx, ∆\({G}_{b}\), and ∆\({G}_{p}\) are well supported with each other. For the quinizarin and NaDS system, the obtained ∆\({G}_{b}\) values are − 19.08 kJ mol−1 at 293.15 K and − 20.40 kJ mol−1 at 303.15 K, where the ∆\({G}_{p}\) values were found − 31.06 kJ mol−1 at 293.15 K and − 32.92 kJ mol−1 at 303.15 K97. Olaseni et al.116 reported that for the Crystal Violet (CV) dye + NaDS system, the obtained values of ∆\({G}_{b}\) and ∆\({G}_{p}\) are − 8.42 kJ mol−1 and − 33.2 kJ mol−1 respectively. The reported values for the BNP + NaDS mixed system are − 10.86 kJ mol−1 for ∆\({G}_{b}\) and − 28.6 kJ mol−1 for ∆\({G}_{p}\)107. The observed ∆\({G}_{p}\) value is − 26.38 for the RY86 + NaDS system108 and − 25.53 kJ mol−1 for the hemicyanine dye + NaDS system105. Thus, our findings disclose the analogy with the reported values97,105,107,108,116.

Conclusions

This research has explored the significant impacts of buffer solution (different pH) and four different potassium electrolytes (KCl, KNO3, KHSO4, and K2SO4) as well as temperatures on the association and binding/portioning characteristics of NaDS with OFC drug by means of conductometric and UV–Visible spectroscopic techniques. The addition of different potassium salts greatly affected the assembly of NaDS in aqueous solution of OFC drug. The micelle development has been found to be facilitated in the attendance of K-salts employed in the experimental system which was realized from the gradual declining of CMC values with the upsurging of salts contents. The augmentation of experimental temperatures caused the rise of CMC values where the CMC versus T plots demonstrated a nonlinear line pattern. At higher temperatures, the micellization process was observed to be delayed and the larger amount of amphiphile was being necessitated to create the micelle species. The greater values of Kx revealed that the remarkable transfer of OFC drug from water to the NaDS micellar phase, which was affected by the presence of KCl and temperature variation. The negative magnitudes of \({\Delta G}_{m}^{0}, \Delta {G}_{b},\) and \(\Delta {G}_{p}\) were attained which indicated the spontaneous behavior of micellization, binding and partitioning respectively in the experimental system. The \({\Delta H}_{{\varvec{m}}}^{0}\) and \(\Delta {S}_{{\varvec{m}}}^{0}\) data indicated that the primary interactive forces between NaDS and OFC species were hydrophobic and electrostatic in nature. Different thermodynamics properties of transfer (\({\Delta G}_{m,tr}^{0}\), \({\Delta H}_{m,tr}^{0}\), \({\Delta S}_{m,tr}^{0}\)), molar heat capacity \({(\Delta C}_{m}^{0}),\) compensation temperature (Tc) along with intrinsic enthalpy gain (\({\Delta H}_{m}^{0,*}\)) were calculated and evaluated accordingly which provided significant information on the nature and behaviors of the experimental surfactant-drug system. The significant findings of this study will be highly useful to understand the stability and release kinetics of a large variety of drugs compounds used in curing of different diseases in human body. The formulations of drugs should be accomplished with the consideration of various ingredients available in human body fluids to maintain the CMC values of the surfactants used as excipient. The effects of different electrolytes present in the blood stream such as \({\text{Na}}^{+}\), \({\text{Ca}}^{2+}\), \({\text{PO}}_{4}^{3-}\) etc. need to be studied more in near future using other important techniques such as surface tension measurement, SEM, TEM and molecular dynamics method to gain further insights and proper understanding of electrolytic impacts on the aggregation behaviors of NaDS + OFC mixed system.