Colloid and Interface Science Communications 28 (2019) 41–48

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Colloid and Interface Science Communications

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Chloramphenicol Loaded Microemulsions: Development, Characterization T

and Stability
Muhammad Abid Rashida, , Tehreem Naza, Madeeha Abbasa, Sadia Nazirb, , Nafisa Younasa,
⁎ ⁎

Sana Majeeda, Naseem Qureshic, Muhammad Nadeem Akhtard

a
Department of Chemistry, University of Agriculture, Faisalabad 38040, Pakistan
b
Department of Chemistry, Govt. College Women University, Faisalabad, Pakistan
c
Department of Chemistry, Karakoram International University, Gilgit 15100, Pakistan
d
Faculty of Industrial Sciences & Technology, University Malaysia Pahang, Pahang 26300, Gambang, Malaysia

ARTICLE INFO ABSTRACT

Keywords: This study aimed to formulate and characterize microemulsions containing chloramphenicol. Microemulsions
Microemulsions represent highly biocompatible drug delivery systems due to their potential for increased absorption as well as
Novel carrier high solubilization capacity. MEs were composed of Oleic acid, non-ionic surfactants tween 20/60, 1-propanol
Chloramphenicol and phosphate buffer. The optimum weight ratios of components and MEs areas were determined by pseudo-
Drug location
ternary phase diagram. All formulations were physically characterized by centrifugation, pH, refractive index,
Stability
conductivity, viscosity, surface tension and partition coefficient. The specific residence site of chloramphenicol
was detected by 1H NMR study. It was uncovered that drug is entrapped between the oxyethylene groups of
hydrophilic shell of MEs. So, the drug was screened from bulk water and its stability was enhanced. Thus, all
characterizations have suggested that formulated MEs have potential for ocular application, being able to use as
efficient drug carrier for ocular drug delivery.

1. Introduction contents of chloramphenicol are < 0.25% [6]. So, it is challenging

objective to develop aproficient ocular drug carrier which can offer
The eye is unique in its therapeutic challenges [1]. Ocular diseases enhanced stability, bioavailability and prolonged drug residence time.
are most widely treated by the topical application of ophthalmic solu- In last few decades microemulsions (MEs) are emerged as a pow-
tions in the form of eye drops. The available ophthalmic solutions ac- erful drug carrier because of their unique properties [7]. MEs are
count for 90% of conventional dosage forms [2]. One of the major transparent, optically isotropic and thermodynamically stable disper-
concern of conventional eye drops (solutions, suspensions, etc.) is the sions which posses' small droplet size (5-200 nm) and low surface ten-
meager bioavailability (< 5%) due to high tear fluid turnover and sion, which may result in improved permeation and high drug ab-
drainage from eyes due to its physiology [3]. Hence the topical eye sorption. Hence there is strong possibility to deliver drug to the
drops do not penetrate into the internal segments of eyes [4]. The posterior segment of eye [8]. Scientifically, microemulsion is a disper-
corneal barrier and drainage from eyes reduces the worth of a useful sion of oil, surfactant and water [9]. MEs form spontaneously and
drug, these concerns could be ameliorated by the application of novel contain distinct boundary between water phase and oil phase and at the
pharmaceutical delivery systems. boundary surfactant is located. MEs can be a good liquid membrane
Environmental air pollution is source of many bacterial infections carrier for the transport of hydrophilic substances across the lipoidal
causing irritation, inflammation and burning of eyes. Chloramphenicol mediums and to carry the hydrophobic substances through the aqueous
is one of antibacterial agents which are used to treat the ocular infec- medium [10].
tions. Chloramphenicol is originally isolated from the certain strains of It is critical to select a novel dosage form because a useful drug
Streptomyces Venezuelae. It performs its action as bactriostatic antibiotic becomes worthless due to poor drug carrier. Therefore, in this research
and shows broad action spectra against gram-positive and gram-nega- plan efforts have been made to formulate a drug carrier which is cap-
tive bacteria [5]. Chloramphenicol is easily hydrolyzed into glycol in able of targeted delivery with high therapeutic efficacy. Since, new MEs
conventional eye drops. The eye drops are turned unqualified if the composed of oleic acid/Tween 20/Tween 60/n-propanol/phosphate

⁎
Corresponding authors.
E-mail addresses: [email protected] (M.A. Rashid), [email protected] (S. Nazir).

https://doi.org/10.1016/j.colcom.2018.11.006
Received 16 August 2018; Received in revised form 3 November 2018; Accepted 20 November 2018
Available online 27 November 2018
2215-0382/ © 2018 Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
M.A. Rashid et al. Colloid and Interface Science Communications 28 (2019) 41–48

buffer were developed for enhancing the stability and bioavailability of 2.3.6. Surface Tension Measurement
chloramphenicol. Pseudo-ternary phase diagram was delineated to find Stalagmometerwas used to determine the Surface tension values by
the microemulsion zone. The 1H NMR spectroscopy was used to find the drop number method [11]. Number of drops of water and each for-
location of chloramphenicol in microemulsions. In addition physico- mulated MEs were counted, than the surface tension was calculated by
chemical characteristics were also analyzed and it is expected that using this formula
microemulsion system may enhance the bioavailability of chlor- n2d1
amphenicol and prevent the degradation of it. 1 = 2
n1d2 (1)

2. Materials and Methods γ1 = surface tension of microemulsion γ2 = surface tension of

water.
Chloramphenicol drug was purchased from Unesco Pharmaceutical n1 = no. of drops of microemulsion n2 = no. of drops of water.
Industry Lahore, Pakistan. Polyethylene glycol sorbitan monolaurate d1 = density of microemulsion d2 = density of water.
(Tween 20: CAS, 9005-64-5) and Tween 60 Polyoxyethylene sorbitan
monostearate (Tween 60: CAS, 9005-67-8) were from Sigma Germany 2.3.7. Viscosity measurements
and both were of analytical grade. Oleic acid (CAS, 112–80-1, EP NDJ-8S rotary viscometer was used to measure dynamic viscosities
Grade), 1-propanol (CAS, 71-23-8, GR Grade 99.5%) and phosphate of all formulated MEs at 25°С.
buffer standard solution (PB, pH = 7) were purchased from Dae-Jung
Korea. 2.3.8. Partition coefficients
Oil/buffer partition coefficients were inspected by dissolving 20 mg
chloramphenicol in 7 mL isopropyl myristate. Buffer was added in it
2.1. Microemulsion Formulation
(1:1 ratio v/v). The mixture was shaken well for 10 min and centrifuged
for 2 h. The two layers were separated and the content of chlor-
Pseudo-ternary phase diagram was mapped using oil (Oleic acid;
amphenicol in aqueous layer (PB) was assessed by UV–visible spectro-
HLB = 16), surfactant (Tween 20; HLB = 14.5), co-surfactants (Tween
photometer at 278 nm (λmax of drug). The two layers were assessed by
60; HLB = 15) and 1-propanol and phosphate buffe (PB) as an aqueous
Perkin Elmer Lambda 25UV/VIS spectrophotometer at 278 nm [12].
phase (pH = 7.0) at room temperature (25°С). In the start, oleic acid
was mixed with Tween 20/Tween 60/1-propanol and then PB was
2.3.9. 1H NMR Spectroscopy
added drop-wise to obtain the ME. Transparent and Single phase and 1
H NMR experiments were performed on a Bruker spectrometer at
transparent mixtures were selected as microemulsions. All the samples
600 MHz. Chemical shifts of all microemulsions determined by using
were clear and stable for a period of upto 6 months.
D2O as solvent.

2.2. Incorporation of Drug in Microemulsions 3. Results and Discussion

MEs loaded with 5% (w/w) of chloramphenicol were formulated by In present study the MEs system is composed of oleic acid as oil
dispersing drug in oil phase, then adding in the mixture of surfactants phase, tween 20/60 surfactants and 1-propanol as cosurfactant. The
and co-surfactants. The phosphate buffer was added drop wise to this choice of dispersed phase for ocular drug delivery is very important
mixture followed by constant stirring at ambient temperature. 8 for- because it governs both the solubilization of drug and existence of
mulations were obtained. microemulsion. The oil phase also influences the curvature, so it is
necessary to select an appropriate oil phase. Therefore oleic acid is
2.3. Characterization of Microemulsions selected as oil phase because of its solubilization potential and it is well
tolerated by the eye [13]. Selection of surfactant is also a critical step to
2.3.1. Optical Brightness design a ME system. There should be appropriate lipophilic character of
The optical isotropy and homogeneity of pure and drug loaded MEs surfactant to facilitate the right curvature at the interface of ME droplet.
was examined by a polarimeter(Code 36-222 made in UK, Bellingham Generally, for O/W MEs the surfactant with high HLB (> 12) are sui-
Stanley limited) and visual evaluation at RT (25°С). table [14]. Non ionic surfactants are widely used in pharmaceutical
preparations and these are also nontoxic and irritations free [15].
2.3.2. Stability Study Therefore, Tween 20 (HLB = 14.5) and tween60 (HLB = 15) were
Thermodynamic stability of pure and drug-loaded MEs was de- chosen to formulate these MEs. The flexibility of interface is the major
termined by centrifugation at 3000 rpm for 20 min using 80–2 CENT- consideration in development of MEs. If the interfacial film is rigid, the
RIFUGE. formation of microemulsion is prevented. For this reason co-surfactants
are often combined with surfactants [10].The requirement of additional
input of energy is overcome by short chain alcohols [16] and alcohols
2.3.3. pH
also influence the activity of nonionic surfactants in micellar state [17].
The pH values of all the formulated MEs were measured with Digital
An oil solution without aqueous phase was formed when a mixture
Multimeter fitted with a pH electrode. All the values were taken at
of oil, surfactant and cosurfactant was blended. 1-propanol an alcohol
25°С.
interacts with the ethoxylated head region of tween 20 and tween 60
and develops hydrogen bonding which controls the packing para-
2.3.4. Refractive Index meters. When aqueous phase is added to this oily solution the hydrated
The refractive indices of all formulated MEs were evaluated by using head groups of tween 20 are organized into a polar core so 1-poropanol
a refractometer (ATAGO, RX-5000) at wavelength approximate to D- prevents the lyotropic crystal formation. In the start water in oil mi-
line(589.0 nm) and 25°С. croemulsion are formed which then turned into bicontinuous phase and
then on further dilution converted into oil in water microemulsion
2.3.5. Conductivity Measurements without any phase separation.
The values of conductivities were measured by a Conductivity Meter The relationship between the phase behaviour of a mixture and its
(HANNA HI 9811-5) fitted with an electrode (HI 1285-5) at 25°С to composition can be captured with the aid of a phase diagram. The
determine the type MEs. pseudo ternary phase diagram was mapped and area of existence of ME

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M.A. Rashid et al. Colloid and Interface Science Communications 28 (2019) 41–48

Fig. 1. Pseusdo-Ternary phase diagram and microemulsion region of microemulsions composed of oleic acid, tween 20/60/1-propanol and phosphate buffer.

Table 1
Optimized microemulsion formulations.
Microemulsion Oleic acid (w/w%age) Surfactant (Tween Co-surfactanta (w/w%age) Co-surfactantb (w/w%age) Phosphate buffer (PB)
(ME) 20) (w/w%age) (w/w%age)

1 0.1 1 0.42 0.1 8.38

2 0.2 1.21 0.5 0.2 7.89
3 0.3 1.51 0.8 0.4 6.99
4 0.4 1.8 1 0.6 6.2
5 0.5 2.2 0.8 0.61 5.88
6 0.6 2.6 1 0.8 5
7 0.7 2.84 1.2 0.9 4.36
8 0.8 2.05 1.4 1 3.85

a
Tween60.
b
1-Propanol.

consisted of Oleic acid/Tween 20/Tween 60/1-propanol/PB is shown in formulated MEs have maximum shelf life of six months. The pH values
Fig. 1. The microemulsion was formed by the spontaneous mixing of all are adjusted by using phosphate buffer (pH = 7) as aqueous phase, the
components at room temperature. Eight formulations were carried out buffer solution also enables the eye to maintain the pH within the
from one phase isotropic region in Fig. 1 and compositions of selected physiological range [19]. For topical formulations the ocular comfort
microemulsions are described in Table 1. pH ranges from 6.6 to 7.8 due to limiting buffering capacity of eyes
[20]. Since the pH of eye drops applied as therapeutic substance vary
3.1. Optical Brightness from 3.5 to 8.5, so the pH values of formulated MEs were in the ac-
ceptable and tolerable range and meet the requirements of ophthalmic
The homogeneity and optical isotropy of all pure and drug loaded delivery system [21].
MEs were examined at 25°C. All the samples were clear and transparent
single phase solution and also all the MEs were remained stable. 3.4. Refractive Index

3.2. Stability Study The refractive index of tear fluid must not be higher than 1.476 with
an optimum value of 1.404 [21]. The refractive indices of pure and drug
Adequate physical stability was shown by all the formulated MEs loaded MEs were ranged from 1.35433–1.41948 and 1.35379–1.41714
after centrifugation at 3000 rpm for 20 min. So, it revealed that all the respectively as shown in Table 2. So the refractive indices of the pre-
components of MEs were compatible and there was no discrete altera- pared drug loaded MEs were within the tolerable range of tear fluid.
tion in the transparency of all formulations. Therefore, after the administration of microemulsion, there will be no
discomfort and any impairment of vision [22].
There was a slight change in the refractive index of each formula-
3.3. pH
tion after the drug loading. This slight change indicated that the drug
has successfully loaded on microemulsion system without any phase
Stability of formulated microemulsions, the activity of product,
changes in this multicomponent system.
comfort safety, drug preservative efficacy and drug bioavailability all
are affected by the pH value [18]. So, the pH of ophthalmic formula-
tions should be adjusted close to the pH of tears. The pH values of all 3.5. Conductivity Measurements
formulated neat and drug loaded MEs were ranged from 5.49 to 6.49
and 5.65–6.43 respectively. At these pH values all neat and drug loaded The human body has hydrophilic physiological environment, so the
microemulsions were stable and there was no phase separation and all chloramphenicol should be incorporated in oil in water microemulsion

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M.A. Rashid et al. Colloid and Interface Science Communications 28 (2019) 41–48

Table 2
Values of the physicochemical parameters characterizing the neat and drug loaded microemulsions.
ME pHa,b Refractive Indexa,b Conductivitya,b (mS) γa,b (mN/m) Viscositya,b (mPa.s)

a b a b a b a b a b

1 6.43 6.49 1.35433 1.35379 1.41 1.99 36.7 37.9 54 51

2 6.24 6.29 1.35933 1.35702 1.49 1.66 36.5 36.6 62 64
3 6.1 6.11 1.36946 1.37177 1.14 1.15 31.5 32.6 74 76
4 5.96 5.88 1.38187 1.38086 0.84 0.77 28.2 30.1 85 88
5 5.83 5.75 1.38471 1.41714 0.67 0.69 28.7 29.9 97 101
6 5.75 5.7 1.40665 1.34549 0.50 0.41 29.5 29.3 107 110
7 5.53 5.67 1.40443 1.38482 0.28 0.37 31.2 26.9 117 121
8 5.65 5.49 1.41948 1.3661 0.17 0.18 28.7 26.2 128 133

a
Neat microemulsions.
b
Drug loaded microemulsions.

for its ophthalmic application. Therefore, it is necessary to inspect the ocular bioavailability of chloramphenicol can be increased as compare
phase behavior of formulated MEs. The conductivity measurements are to commercial eye drops.
used to determine the type of MEs whether it is water-continuous or oil- Viscosity values also influence the stability of formulations so op-
continuous [23]. The conductivity values of pure and drug loaded MEs timum viscosity values are required for good stability. As viscosity in-
were ranged from 1.14–0.17 mS and 1.99–0.18 mS respectively. Such creases there will be reduction of globule's flocculation due to restricted
higher values of conductivities proved that all the formulated micro- mobility and hindered Brownain movement, leading to creaming [30].
emulsions were oil in water microemulsions. Fig. 2.(a) showed varia- The results depict that within this viscosity range all the formulated
tion of conductivities of formulated MEs. As the concentration of water MEs showed good stability there was no creaming for the period of six
content decreased, the concentration of oil was increased the con- months.
ductivity goes to decrease because the movement of ions became dif-
ficult to conduct. 3.8. Partition Coefficient

3.6. Surface tension Drug transport characteristics, which include distribution, reten-
tion, absorption and elimination, are influenced by partition coeffi-
Surface tension of pure and chloramphenicol loaded MEs were cients. Since the drugs are transported by blood, they must traverse and
varied from 28.2–36.7 mN/m and 26.2–37.9 mN/m respectively penetrate many cells to reach at the site of action. Hence the site of
(Table 2) and graphically represented in Fig. 2.(b). There is a de- action of given compound will be determined by the partition coeffi-
creasing trend in the surface tension values from ME-1 to ME-8. It is cients.
revealed from the results that as the concentration of surfactants is
increased in the formulation it reduced the surface tension values of 3.9. Oil/Buffer Partition Coefficients
pure and drug loaded formulations because the increased amount of
surface active agents at interface led to reduce the interfacial tension The logarithmic values of drug solubilities are called partition
[24]. There is modification of interface properties by the preferential coefficients [Log P] and biopharmaceutical properties of drugs are
adsorption of surfactants [25] which ultimately form a flexible film predicted by it [31]. The partition coefficient (Log P) of chlor-
around the droplets. In comparison to the surface tension of human amphenicol in oil/buffer is 2.4076 ± 0.20. Acocording to Lipinski's
lachrymal fluid (40–50 mN/m) [26] the values of formulated MEs are “rule of five” there will be poor drug absorption and permeation if the
lower which indicate that all formulations can be spread uniformly on partition coefficient is > 5 [32]. The partition coefficients were lower
the corneal surface. The uniform distribution of MEs will ultimately than 5, it showed that the present formulated system is capable of
lead to enhancement of permeability of drug. Hence the absorption area loading efficiency and partitioning of chloramphenicol, to improve in-
will be enhanced and the bioavailability of chloramphenicol will also corporation of drug, to increase the uptake of drug and retention, and
increase. sustained release of drug [33].
The presence of tween 20 (5% in buffer) and co-surfactants (5%-
3.7. Viscosity measurements Tween 60 + 1-Propanol) reduced the partition coefficients to
1.1567 ± 0.15 and 1.2979 ± 0.20 respectively. The concentration of
Viscosity is a fundamental parameter to assess the efficiency of any drug in oil phase was reduced due to the presence of surfactant
formulation (low viscosity reduces bioavaiability due to immediate (Table 3). The partitioning of drug between aqueous and micellar phase
drainage from eye) and its compatibility to eye (high viscosity causes is governed by the hydrophilic-lipophilic balance (HLB) of surfactant.
blinking pain and blurred vision). Viscosity is largely influenced by the The penetration of drug deeply in the micelle is prevented due to the
presence of aggregates, their interaction and concentration. It is well attraction between drug and surfactant [34]. Therefore the drug re-
known that by increasing the dispersed phase in microemulsion the mains localized at the interface of micelle. Thus, the partition studies
viscosity of the system in increased [27]. show that the chloramphenicol may be resided at the interface. The
For reported system there was an increase in viscosity of ME-1 to solubility of chloramphenicol may be increased due to the presence of
ME-8 by increasing the concentration of dispersed phase as shown in drug at the hydrophilic shell of microemulsion droplet. The partition
Table 2 and graphically represented in Fig. 2.(c). It was observed that coefficients were determined by following formula [35]:
the viscosity measurements for all formulations were high than the A (org ) × Vf (org ) × V (aq)
viscosity of other ophthalmic solutions (20 mPa.s) [28]. These low P=
A (aq) × V (org ) × Vf (aq) (2)
viscosity eye drops cause the spillage of drug and lead to low bioa-
vailability, so, it is required to insert the solution many times in a day where A (aq) and A (org) is the absorbance of aqueous and organic
[29]. Thus to reduce the instillation frequency per day these MEs were layer, V (org) and V (aq) is the volume of aliquot from organic and
developed with high viscosity so that the drug residence time and aqueous layers, Vf (org) and Vf (aq) is the final volume of sample from

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M.A. Rashid et al. Colloid and Interface Science Communications 28 (2019) 41–48

Fig. 2. a) Variation of electrical conductivity for neat and drug loaded MEs; b) Variation of Surface tension for neat and drug loaded MEs at 25 °С; c) Variation of
viscosity for neat and drug loaded MEs at 25°С.

Table 3 organic and aqueous layer.

Oil/buffer partition coefficient of Chloramphenicol (mean ± S.D). The standard free energy ΔGopcan be calculatedfor the transfer of
System P log P ΔGop = -RTlnP
additive to micelle from bulk aqueous phaseby using following equa-
(kJ/mol) tion [36]:

Oil/buffer 2.5568 × 102 2.4076 ± 0.20 −13.73

Go p = RTlnP (3)
Oil/buffer(5% Tween 20) 1.4346 × 101 1.1567 ± 0.15 −6.60
Here T absolute temperature and R denotes the gas constant.
Oil/buffer(5% Tween 1.9856 × 101 1.2979 ± 0.20 −7.40
60 + 1-Propanol) The spontaneity of solubilization is expressed by this parameter, a
negative value indicates the spontaneous transfer of drug to micelles
[37]. The values of standard free energy ΔGop for chloramphenicol,

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M.A. Rashid et al. Colloid and Interface Science Communications 28 (2019) 41–48

Fig. 3. Structures of (a) chloramphenicol, (b) tween 60 and (c) tween 20.

Table 4
1
H NMR chemical shifts values for surfactants in microemulsion with different concentration.
Functional Group δ(ppm)

δ0 δ1 δ2 δ3 δ4 δ5 δ6 δ7 δ8

ω-CH3 0.7642 0.7773 0.7638 0.7752 0.7756 0.7734 0.7773 0.7792 0.7754
(CH2)n 1.1664 1.1737 1.1715 1.1691 1.1713 1.1092 1.1708 1.1716 1.1684
β1-CH2 1.2173 1.4729 1.4662 1.4633 1.4664 1.3709 1.4639 1.4647 1.4599
α1-CH2 2.2789 2.2120 2.2085 2.2028 2.1191 2.0434 2.2056 2.2085 2.2025
(CH2CH2O)n 3.6303 3.5253 3.5257 3.5228 3.5234 3.5487 3.5264 3.5264 3.5239
α2-CH2 4.1480 4.0395 4.0340 4.0903 4.0366 3.9736 4.0344 4.0402 4.0908

δ0chemical shifts for surfactants of pure microemulsion,δ1-δ8 chemical shifts for surfactants of microemulsion loaded with drug 5–12%wt with respect to oil con-
centration.

Table 5
Difference of chemical shifts values for surfactants in microemulsion by loading chloramphenicol.
Functional Group δ(ppm)

δ0−δ1 δ0−δ2 δ0−δ3 δ0−δ4 δ0−δ5 δ0−δ6 δ-0δ7 δ0−δ8

ω-CH3 −0.0131 0.0004 −0.011 −0.0114 −0.0092 −0.0131 −0.015 −0.0112

(CH2)n −0.0073 −0.0051 −0.0027 −0.0049 0.0572 −0.0044 −0.0052 −0.002
β1-CH2 −0.2556 −0.2489 −0.2460 −0.2491 −0.1536 −0.2466 −0.2474 −0.2426
α1-CH2 0.0669 0.0704 0.0761 0.0735 0.2355 0.0733 0.0704 0.0764
(CH2CH2O)n 0.1050 0.1046 0.1075 0.1069 0.0816 0.1039 0.1039 0.1064
α2-CH2 0.1085 0.1140 0.1123 0.1114 0.1744 0.1136 0.1078 0.1107

using P, are given in Table 3. The more negative value of ΔGop indicated residence site of chloramphenicol has been determined by proton NMR
that the partitioning of chloramphenicol is spontaneous and the system spectroscopy of microemulsion system consisting of Oleic acid (oil
is stable. phase), Tween 20 (as surfactant), tween 60 + 1-propanol (as co-
surfactant) and PB (as aqueous phase). The composition of selected ME
3.10. 1H NMR Study was fixed and the concentration of chloramphenicol was varied from 5
to 12% wt with respect to oil contents. In this system oleic acid, tween
More recently, the NMR techniques has been used to characterize 20 and tween 60 have many oxyethylene groups and long hydrocarbon
the colloidal systems of pharmaceutical importance e.g. MEs. To de- chains. So many functional groups (ω-CH3,α1-CH2, β1-CH2, (CH2)n, α2-
termine the locus of drug in the microemulsion interior, we reported CH2and CH2CH2O)n) (Fig. 3) and many molecules resulted complex
here different results of 1H NMR study. Different proton chemical shifts NMR spectra. The results obtained from NMR spectra are summarized
were originated due to surrounding electronic environment. So the in Tables 4. and 5. It was noted that there was a change in the chemical
change in chemical shifts may serve as a sensitive probe for determi- shifts of certain groups of surfactants by the addition of chlor-
nation of drug location and its local interactions. Therefore the possible amphenicol. This study revealed that the chemical shifts of oxyethylene

46
M.A. Rashid et al. Colloid and Interface Science Communications 28 (2019) 41–48

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