Review Article
A Brief Review on Solubility Enhancement Technique:
Hydrotropy
Bhavesh Namdev1, Senthil Venkatachalam1,*, N Jawahar1, Anushma Chorsiya2
1
Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty,
Nilgiris, Tamil Nadu, INDIA.
2
Department of Pharmacognosy and Phytochemistry, Delhi Pharmaceutical Sciences and Research University, New Delhi, Delhi, INDIA.
ABSTRACT
In this review we have elaborated about number of hypothesis postulated to understand
the mechanism of hydrotropic agents, although majority of the postulated hypothesis
haven’t justified the solubility enhancement mechanism. Further to it the articles focuses
upon the parameters affecting enhancement of solubilizing ability. Hydrotropes are
extensively used in drug solubilization, extraction agents for various phytoconstituents,
separation agent used for pharmaceutical analysis, as well as for increasing the rate and
yield of a chemical reaction due to their unique features. Because of this, hydrotropic
solutions possess high industrial demand. While mixed hydrotropy is mostly used in
enhancement of solubility, extraction of phytoconstituents and separation by the use
of more than one hydrotropic agent. This review article also highlights the applications
and future prospects with the employment of hydrotropes and hydrotropic agents in
novel drug delivery or parental or oral or tropical systems to enhance solubility profile the
drugsare also discussed.
Key words: Mixed Hydrotropy, Solubilizing agent, Mechanisms of hydrotropes, Application
of Hydrotropes, Solubility, Bioavailability enhancement.
INTRODUCTION
Agents that are employed to enhance
solubility of solutes which are poorly soluble
in solvents are termed as hydrotropes or
hydrotropic agents.1 Solubilization is a
process that involves molecular interactions
that are balanced by various forces at
molecular level, it cannot be explained
as a simplex complication process or
phenomenon that are greatly influenced by
effect of medium comprising of salting-in
or co-solvency.2 To increase solubility,
processes like salting-in and salting-out
are majorly employed. Salts demonstrating
process of ‘salting in’ of non-electrolytes are
defined as “hydrotropic salts” and the event
is described as “hydrotropism” this salting-in
is contrasting to salting-out.3 Hydrotropic
salts intensify the solubilizing property of
the solute by establishing a weak interaction
with them, although no colloidal property is
exhibited due to interaction.4 Hydrotropes,
resembles properties of surface active
agents,5 which enhances aqueous solubility
of solutes that are sparingly water soluble
under room temperatures. Hydrotropy has
potential to develop itself as an industrial
technique.6
The majority of studies on the mechanism
of hydrotropic solubilization focuses
on potential interactions between the
hydrotropes and the solute which concludes
that the solubilization is due to complexation
between the two.1 We can easily correlate
hydrotropy as a solubilization process which
enhances aqueous solubility of a solute which
is dependent over the addition of another
solute (hydrotropic agents).1 Hydrotropes
generally employed are tetraalkylammonium
halides, urea, nicotinamide, aromatic
sulfonates, guanidinium chloride, sodium
thiocyanate etc.7 Hydrotropic agents can
be characterized as an ionic organic salts
which on addition to the solvent may either
cause increment in the solubility profile of
Indian Journal of Pharmaceutical Education and Research | Vol 56 | Issue 2 | Apr-Jun, 2022
Submission Date: 13-08-2020;
Revision Date: 31-10-2021;
Accepted Date: 28-01-2022.
DOI: 10.5530/ijper.56.2.54
Correspondence:
Dr. V Senthil
Department of Pharmaceutics, JSS College of
Pharmacy, JSS Academy
of Higher Education and
Research, Ooty-643001,
Tamilnadu, INDIA.
E-mail: senthil.v@jssuni.
edu.in
www.ijper.org
347
Namdev, et al.: Solubility Enhancement Technique: Hydrotropy
a solute or may decrease solubility as well.8 Numerous
studies have proven that hydrotropes to be a reliable
technique for enhancing solubility of drugs or any
solute or organic solvents also that have poor aqueous
solubility profile or are not at all soluble in aqueous
solutions. Hydrotropes may be studied and investigated
further as an additive as it has surfactant like property in
both aqueous as well as oily phases; it can also act as a
carrier for API. Further research may also deal with the
capability of hydrotropes which leads to the formation
of a aggregated structure in hydrophilic system due to
non-covalent bonding.9-11
Various researchers concluded that hydrotropes are
amphiphilic in nature as they have two-parts i.e. one
polar and another nonpolar in one single molecule.
Comparative study determined non-polar portion to be
smaller than polar portion.9 Other study demonstrated
that properties of hydrotropes and surfactant were
linked with a slight system variation in the molecular
structure.10 Hydrotropic agents are characterized
structurally as short, bulky and compact moiety which
differs them from surfactants that consists of long
hydrocarbon chains.12 Researcher also demonstrated that
hydrotropes may be distinguished as cationic, anionic, or
neutral molecule.11
The concept of mixed hydrotropy was developed
cause of its cheapness, non-toxicity and ecofriendly nature which ultimately resulted in solubility
enhancement miraculously due to synergistic action of
the hydrotropic agents. This characteristic property of
mixed hydrotropes give it an edge over simple
hydrotropy, resulting in increased percent yield of
constituents in the process of extractions as well as in
separation techniques like that of chromatography.14
In this review we will be focusing over hydrotropes and
hydrotropic agents, possible mechanisms by which they
enhance solubility of the drug in solvent and various
parameters of hydrotropes. We will also be lime lighting
the importance of the technique in pharmaceutical
industry and also discussing its advantages and
disadvantages.
(c) Self-association of hydrotropes.
But, they haven’t justified the mechanism of hydrotropes.
Furthermore, several researchers postulated various
hypothesis to understand mechanism of hydrotropes,
some of which are explained below:
Hydrotrope self-aggregate formation
This theory postulates that the molecule of the
hydrotropes self-aggregates themselves, which paves
the way for the formation of organized clusters in the
hydrophilic solution. It was also suggested that solutes
molecules get entrapped in these organized clusters
leading to enhancement of solute hydrophilicity.16,17
While the critical concentration at which hydrotropes
begins to aggregate themselves is described as Minimum
Hydrotropic Concentration (MHC).4 Presumptions were
made that planar aromatic rings found in the molecular
structure of the hydrotropes mounds one over the
other for aggregation. As hydrophobic compound
solubilization initiates, the phenomenon of aggregation
also takes place simultaneously in the aqueous solvent,
similarly to that of micellization process. The selfaggregation of the hydrotropes has been considered
to be a pre-requisite for several applications in various
meadows such as drug solubilization. Aggregation of
hydrotropes is accompanied by change in enthalpy,
entropy and free energy.18,19
Alteration of the water structure
Proposed by Frank and Evans, who explained that
hydrotropes do not bind themselves directly with
poorly or sparingly soluble solutes, but they break water
structure which prevents formation of iceberg.16,17
Formation of solute-hydrotrope complexes
Solubilization takes place due to weak complexation
between the non-polar compound and the hydrotrope,
which results in higher aqueous solubility.20 These
complexation hypothesis claims low stoichiometry
complexes (such as 1:1 or 1:2) as the origin of
hydrotropy.16,17
Accumulation of hydrotrope around the drug
MECHANISM OF HYDROTROPE
Mode of action of hydrotropes are by far not clear, as
it is still under debate and far behind from conclusive.
Many researchers gave their own hypothesis about the
possible mechanism of hydrotrope. Three hypothesis
postulated to explain hydrotropic activity are as follows:
(a) Complex formation between solute and hydrotrope,
(b) Disintegrating or shattering tetrahedral complex of
water molecules,
348
Several compounds have been employed to determine
the mechanism of hydrotrope via different experimental
studies employing additives which demonstrated
strong interaction between solute and additive that
leads to micelles formation thus, acting as a bridge
and concentrating around hydrophobic solute without
interaction.7 some other mechanisms include:
(a) Formation of compound between hydrotropes and
dissolved solute,
Indian Journal of Pharmaceutical Education and Research | Vol 56 | Issue 2 | Apr-Jun, 2022
Namdev, et al.: Solubility Enhancement Technique: Hydrotropy
(b)Formation of molecule complex at low hydrotrope
concentration,
(c)Molecular aggregation of hydrotrope due to
electrostatic forces of donor-acceptor type between
hydrotrope and solute molecule,
(d) Stake-type aggregation.5
PARAMETER OF HYDROTROPY
Minimum Hydrotropic Concentration (MHC)
MHC can also be explained as the hydrotropes
concentration which significantly enhances the
solubility of the poorly water-soluble solutes,19 effective
concentration of the hydrotropes can do miracles as
it enhances solubility of solute many folds. It was also
noted that above MHC hydrotropes tends to aggregates
themselves similar to the phenomenon of micelle
formation beyond CMC as seen in case of classical
surfactants.15
Maximum Hydrotrope Concentration (Cmax)
Cmax can be explained as the concentration of
hydrotropes in hydrous phase, beyond which there will
be no significant increase in the solubility of the solute.22
The solubilization effect depend upon the concentration
of individual hydrotropes.
Setschenow constant, Ks
Empirical formula which was established in 188918
helped to determine the efficiency of the hydrotrope
at a particular concentration when introduced into the
solvent.6 “Salting constant” is also sometimes referred
as Setschenow constant. It not only co-link solubility
variation of a solute in correlation of a particular
hydrotrope but also elaborates about the effect of
combination of salts. Later, this model was suggested
by Setschenow and further improvised by Gaikar and
Pathak, who proposed an equation:
IMPORTANCE OF HYDROTROPY
Hydrotrope solution can be regarded as a green
solvent as they are cheap, easy to handle, non-toxic and
environmentally friendly. Averting the use of organic
solvents is one step closer for increasing the solubility
in hydrotrope i.e., avoiding the use of organic solvents;
aqueous solutions of hydrotropes demonstrated the
unique features of an alternative reaction media for
organic synthesis, as organic solvents were frequently
employed which may be sources of pollution while
some of them may be toxic, costlier also. While volatility
may also lead to inaccuracy.13,25-27
APPROACH
By use of different solubilization approaches such
as solid dispersion that enhances the solubility, by
thermodynamic as well as molecular approach. Various
approaches are been targeted in the field of science
like in pharmacognosy, here, hydrotropes are employed
as solvent for extraction of drug, while in analytical
field mixed hydrotropes helped in identification, novel
separation technique, spectrometric analysis, HPLC
and many other instrumental approaches and in the
field of pharmaceutical science, hydrotropes are used
in formulation and estimation processes. Mostly
hydrotropes and mixed hydrotropy are effectively used
in the chemistry for various purposes that are linked
to thermodynamics, mass coefficient, temperature
studies, concentration phenomenon, green solvent,
pH-dependent study, micelle formation, etc. On the
other hand industrial scenario of the hydrotrope is
entirely different as it was used in cleaning and personal
care product formulation but in pharmaceutical industry
hydrotropes are used for “green synthesis” for the
formulation of dosage form and various approaches in
the formulations of dosage form (examples, parenteral,
oral, transdermal, nasal, etc).
Pharmaceutical application
LogS/Sm =Ks [Cs−Cm]
Where S and Sm = solubility of compound at any
hydrotrope concentration and Cs = Concentration of
salt.18
Effect of temperature
Determining the effectiveness of the hydrotrope
concerning the different range of temperature, is also
measured in terms of Setschenow constant.
In Table 1, some of the hydrotropes are summarized
with their MHC, Cmax, Setschenow constant (Ks) and
Maximum enhancement factor.
In the field of pharmaceutical science, hydrotropes have
been used for the preparation of drug formulation as
well as to stabilize them. Hydrotropes have found their
application in manufacturing of parenteral, oral, topical
as well as in novel drug delivery system also. It is mainly
employed for drugs that have solubility issues. Some
of the examples are described in Table 2 that showed
increased solubility of drug, when employed with
hydrotropes.
Analytical application
In analytical chemistry, to avoid or prevent use of
organic solvents and enhance aqueous solubility of the
Indian Journal of Pharmaceutical Education and Research | Vol 56 | Issue 2 | Apr-Jun, 2022
349
Namdev, et al.: Solubility Enhancement Technique: Hydrotropy
Table 1: Minimum hydrotropic concentration (MHC), Maximum hydrotropic concentration (Cmax), Setschenow
constant (Ks) and Maximum enhancement factor (Φs) of individual hydrotropes.
(Φs)
Hydrotropes
Compound
MHC
Cmax
Diethyl nicotinamide
Aminonitrobenze
0.5
2.4
303k
313k
323k
333k
0.41
0.49
0.50
0.51
17.02
28.1
40.93
56.6
23
Sodium pseudocumene sulfonate
Aminonitrobenze
0.4
2.4
303k
313k
323k
333k
0.41
0.43
0.44
0.46
20.61
28.1
40.93
56.6
23
Sodium thiocyanate
Aminonitrobenze
0.3
2.2
303k
313k
323k
333k
0.43
0.47
0.55
0.59
21.01
29.01
60.75
93.95
23
Rea
Ethylbenzene
0.50
2.20
303k
313k
323k
333k
0.540
0.575
0.561
0.616
12.227
15.763
18.259
23.512
18
Nicotinamide
Ethylbenzene
0.40
2.20
303k
313k
323k
333k
0.598
0.667
0.661
0.668
17.482
22.968
27.254
32.591
18
Sodium Salicylate
Ethylbenzene
0.30
2.40
303k
313k
323k
333k
0.594
0.609
0.661
0.668
28.447
37.219
44.609
52.561
18
Citric acid
-
0.40
2.40
303k
313k
323k
333k
0.481
0.513
0.539
0.565
16.08
21.52
24.82
26.66
22
Tri-Sodium Citrate
Furfural
0.40
2.40
303k
313k
323k
333k
0.338
0.372
0.402
0.424
4.75
5.55
6.38
7.06
6
Sodium Toluate
Furfural
0.60
2.20
303k
313k
323k
333k
0.324
0.363
0.399
0.418
3.30
3.81
3.68
4.07
6
Sodium saccharin
Aminonitrobenze
0.4
2.4
303k
313k
323k
333k
0.41
0.43
0.44
0.46
20.61
32.19
54.18
74.64
23
Dimethylbenzamide
Aminonitrobenze
0.3
2.2
303k
313k
323k
333k
0.43
0.47
0.55
0.59
21.01
29.01
60.75
93.95
23
Sodium benzoate
Aminonitrobenze
0.5
2.4
303k
313k
323k
333k
0.41
0.49
0.50
0.51
17.02
28.1
40.93
56.6
23
Resorcinol
Benzamide
0.50
2.20
303k
313k
323k
333k
0.489
0.525
0.534
0.549
6.77
7.79
8.07
8.58
24
Sodium citrate
Benzamide
0.60
2.20
303k
313k
323k
333k
0.421
0.491
0.521
0.563
4.71
5.12
6.81
7.95
24
350
(Ks)
Reference
Indian Journal of Pharmaceutical Education and Research | Vol 56 | Issue 2 | Apr-Jun, 2022
Namdev, et al.: Solubility Enhancement Technique: Hydrotropy
Table 2: Application of hydrotropy and mixed hydrotropy technique in development of
Pharmaceutical dosage forms.
Hydrotropes and Mixed
Hydrotropes
Concentration and
range
Drug
Solubility
% w/v
Enhancement
Ratio
References
Sodium benzoate + nicotinamide+
sodium citrate
40% = 20:15:5
Carvedilol
5.285
64.451
20
Urea+sodium benzoate+sodium
citrate
40% =15:20:5
Furosemide
5.285
660.625
14
Sodium benzoate+ solvent system
40% = 15:20
Etodolac
-
275.65
28
Sodium benzoate+ sodium salicylate+
PEG 600+ Piperazine anhydrous
10%=2.5:2.5:2.5:2.5
Zaltoprofen
5.251
1875.35
8
Nicotinamide + sodium benzoate +
sodium citrate
40% =15:20:5
Lurasidone
8.93
54.12
11
Urea
8M
Entacapone
7.97
67 fold
29
Piperazine anhydrous
30 %
Valsartan
0.021
30100.4
30
Meglumine
1:10
Glimepiride
1.6
24,000
31
Lactose+ citric acid;
15 : 25
Nevirapine
10.174
102.31
32
3.33 : 3.33 :3.33
Telmisartan
-
15737.5
33
Sodium salicylate.
4.0
Curcuminoids
0.54x10-3
mol/L
144 times
34
Niacinamide
2M
Indomethacin
-
More than five
fold
2
Nicotinamide
10µg/ml
Paroxetine
hydrochloride
-
26.02 and 19.78
l/mol
12
Sodium
Gentisate
1M
Nimesulide
0.1 mg/ml
1173.408 and
747.65 l/moles
35
Urea+ PEG 4000+
PEG 6000
sample, this technique is used. Various methods where
hydrotropes have been used are in • Titrimetric Analysis
• Spectrophotometric Analysis
• Thin-Layer Chromatography
The hydrotropic agent used in the above application are
listed in following Table 3.
Chemistry application
To separate compound, solubility enhancement,
extraction process etc, hydrotropes are employed. And
because of it is eco-friendly, hydrotrope is also use for
green synthesis. For example, determination of first
principles of statistical thermodynamics of hydrotropes
by gibbs phase rule,27 hydrotropes used for determine
the action in micro emulsion.10 Some of the applications
of hydrotrope solution in pharmaceutical chemistry are
summarized in Table 4.
of Rauwolfia vomitoria yield was increased to that of
conventional extraction when hydrotropic agent was
introduced into the solvent. Three different hydrotropes,
Na-CS, Na-PTS and NBBS were employed for the
extraction of reserpine at the same concentration.39
Hydrotropic salts such as sodium salicylate, sodium
cumene sulfonate, sodium phenol sulfonate, sodium
xylene sulfonate, used as a modified hydrotropes for
Lignin extraction from Birch wood. Two treatments
performed, namely as a conventional and a modified
process.40
Computational application
Software are employed to predict the mechanism
by which hydrotropes enhances solubility by using
computer stimulations which is mostly likely predict
results based on the classical molecular dynamic
stimulation technique.15
Pharmacognosy application
Biochemistry application
In the field of pharmacognosy various extraction process
takes place in which hydrotropes assisted extraction
enhances percent yield of the active constituents. For
instance, reserpine which is isolated from the roots
Sodium xylene sulfonate (SXS) and formic acid both
hydrotropes used for pretreatment as they enhance
enzymatic activity. For example, reed when treated with
these hydrotropic agents improvises it’s digestibility.31
Indian Journal of Pharmaceutical Education and Research | Vol 56 | Issue 2 | Apr-Jun, 2022
351
Namdev, et al.: Solubility Enhancement Technique: Hydrotropy
Table 3: Application of hydrotropes in Pharmaceutical Analytical technique.
Method
Dosage Form
Titrimetric Analysis
Bulk Drugs
Titrimetric Analysis
Tablets
Drug
Hydrotropes
Key Finding
Reference
Ibuprofen
8 M Urea
10 Folds Solubility
Enhancement
36
Furosemide
15%Sodium Salicylate
5% Niacinamide,5%
Sodium Acetate 5%
Sodium Citrate
More Than 33 Folds
Solubility Enhancement
37
Quantitative Analysis
Bulk Drugs
Salicylic Acid
Sodium Benzoate 2M
Nicotinamide
Uv-Spectrophotometric
Determination
Bulk Drugs And
Tablets
Metronidazole
8 M Urea
Spectrophotometric
Bulk Drugs and
Tablets
Gliclazide
2M Urea And 6M
Trisodium Citrate
Spectrophotometric
Bulk Drugs and
Tablets
UV Spectrophotometer
Bulk Drugs
UV Spectrophotometry
Tablet
Ornidazole
Spectrophotometry
Bulk Drugs and
Tablets
Acyclovir
Amlodipine
Besylate
Amlodipine
Besylate Celecoxib
Ammonium
Acetate
2M Sodium Benzoate
25% Phenol And 15%
Sodium Benzoate
2% Sodium Benzoate
2% Urea
98.90 ±0.475
98.97 ±0.375
Percentage Drug
Estimate
AUC - 313-323nm
Abs -318
4µg/Ml –12µg/Ml
Concentration Range
225 nm
Maximum Absorption at
362 nm
32 And 26- Fold
Solubility Enhancement
Wavelength Maxima Of
Ornidazole 319 nm
Solubility Increases 2mg/
ml
38
25
39
10
21
22
13
Table 4: Application of hydrotropes solutions in Pharmaceutical chemistry.
Hydrotropes
compound
Sodium salicylate
Sodium benzoate
Xanthones
Styrene
8 M urea
Etoposide
Extracted/separated
from
Mangosteen Pericarp
Styrene-ethyl
benzene mixture
Etoposide tablet
Nicotinamide, resorcinol, sodium citrate
and sodium salicylate
Alkybenzene sulfonates
Cationic hydrotropes
Benzamide
-
Lignin
Vanillin and Gallic acid.
bagasse
-
In Asia, rice strawsare most preferred feedstock
for production of fuel ethanol, are pretreated with
hydrotropic agents NaCS and NaCS. Hydrotropes
solution is a greener solvent and with several advantages,
one of them been an attractive alternative for biomass
refineries. Other advantages linked are quick recovery
of the solute from hydrotrope solutions by simple
dilution with water and reuse of the hydrotrope solution
after recon centration. The various effect carried such
as biomass loading, time, temperature 40 to 80°C and
hydrotrope concentration 10% and 30% were study.22
Artificial neuronal application
In the pharmaceutical sciences, Artificial Neuronal
Network (ANN) which are computational model by the
application of machine learning is of relative important
352
Key finding
Reference
1.14 to 4.69 mg/g yield
69.45 percentage
Extraction
more than 56- and
59-folds solubility
Enhancement of solubility
85 percent delignification
40-fold solubility
enhanced
24
35
16
24
27
38
for the determination and prediction the quantitative
assessment of various hydrotrope physicochemical
properties. For the application of hydrotrope-enhanced
property, use of computational model, predict by
utilization of ANN to determine the role of hydrotropes
in enhancing the solubility of poorly water-soluble
drug.21
ADVANTAGES OF HYDROTROPY AND MIXED
HYDROTROPY
•
•
Less toxic compared to another organic solvent
By the simple and cheap way solubilization done
by using hydrotropes because, it only requires the
mixing of drug substance and particular hydrotropes
both together into the solvent.
Indian Journal of Pharmaceutical Education and Research | Vol 56 | Issue 2 | Apr-Jun, 2022
Namdev, et al.: Solubility Enhancement Technique: Hydrotropy
•
•
•
•
•
•
•
•
•
•
•
•
Answers to solubility problems in a wide variety of
commercial and pharmaceutical applications.
Widespread usage in today’s increasingly complex
formulas.
Main positive aspects of hydrotropic technique is
that it does not hinders with the chemical activity
of the drug substances.
Broad formulation, compatibility and effectiveness,
inexpensive, greener solvent.
Because of their high selectivity over the other
solubilization technique hydrotropy suggested
being superior as a point of safe, cheap, simple,
accurate and precise method.
Mixed hydrotropy preclude the use of an organic
solvent to prevent the problem
For optimum criteria, mixed hydrotropy is one of
the best approaches.
In the field of science hydrotropy having the role
for example used as extraction, separation.
Certain properties of hydrotropes, such as high
selectivity, the solvent character being independent
of pH, emulsification absence.
Facile recovery of the solute from hydrotrope
solutions by simple dilution.
Main benefits of mixed hydrotropy are a
combination of agents by lowering the individual
concentration that should be effective as well as less
toxic.
For solubility of poorly water-soluble drugs mixed
hydrotropy have a synergistic effect on the solubility
of the substance.
DISADVANTAGES OF HYDROTROPY AND MIXED
HYDROTROPY
•
•
There are chances of the weak interaction between
the hydrotropic agent and drugs. As there is the
use of water as a solvent, complete removal of
water cannot be achieved.
The use of hydrotropes is limited for some
hydrotropic agent because of toxicity.
CONCLUSION
Various mechanisms of hydrotropes shows that how
they work up to enhance solubility of a compound that
have poor aqueous solubility, as well as their advantages
and disadvantages have been described thoroughly in
this review. This technique not only paved a way for the
dosage development of the poorly water-soluble drugs
but also helped in the enhancement of the extraction
of the phytoconstituents which have potential
pharmacological activity. Hydrotrope technique has
the ability to replace major conventional techniques
employed in the field of pharmaceuticals because
they act as green solvents that causes less pollution,
environmentally friendly and economically, as well as
they are cheaper than organic solvents. As reviewed in
the field of pharmacognosy this technique can be used
to replace organic solvents and enhance percent yield
of the constituents during isolation, separation and
characterization of compounds. Similarly, in the field
of pharmaceutics, this technique enhanced the aqueous
solubility and increase the bioavailability of poorly
solubilizing synthetic as well as isolated compounds. This
review defines the application of hydrotropes in various
field of science and thoroughly explains proposed
mechanisms of hydrotropic agent. Above studies raises
the use of hydrotropes in the field of pharmaceutics
for further progress in hydrotropy, especially in
formulation of drugs by utilization of hydrotropic
agent towards the enhancement of solubility of poorly
water-soluble drug to enhanced therapeutic delivery.
However, many challenges remain with mechanisms of
hydrotropes and these are still in debate. Basic approach
involves interaction of hydrotropic agent with poorly
water-soluble drug, which boosted solubility as well
as bioavailability. Various experimental Studies have
confirmed that hydrotropic technique can replace
the use of organic solvents. This technology safe and
eco-friendly in nature.
ACKNOWLEDGEMENT
Author acknowledges JSS College of Pharmacy, Ooty
Tamil Nadu for the assistance.
CONFLICT OF INTEREST
The authors declare that there is no conflict of interest.
ABBREVIATIONS
PEG: Polyethylene glycol; Na-PTS: Sodium
p-toulenesulfonate; NaCS: Sodium cumene sulfonate;
NaeX: Sodium xylene sulfonate; ANN: Artificial neural
network; MHC: Minimum hydrotrope concentrations;
Cmax: Maximum hydrotrope concentration; CMC:
Critical micelle concentration; Ks: Setschenow
constant; Φs: Maximum enhancement factor; M: Molar
concentration.
REFERENCES
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Indian Journal of Pharmaceutical Education and Research | Vol 56 | Issue 2 | Apr-Jun, 2022
Namdev, et al.: Solubility Enhancement Technique: Hydrotropy
PICTORIAL ABSTRACT
SUMMARY
The topic covered in this review article were summarized
after extensive search over hydrotropic agents. Various
applications identified are unique enough, which can be
used in pharmaceutical industries for drug development
which could be made environment friendly as well as
can be cost effective with better results. The key aspect
of this review article was to bring light over hydrotropic
agents and their application in various pharmaceutical
divisions. This article may help researchers in their work
to get better result in more eco-friendly way.
About Authors
Mr. Bhavesh Namdev, Department
of Pharmaceutics, JSS College of
Pharmacy, JSS Academy of Higher
Education and Research, Ooty, Nilgiris,
Tamil Nadu, INDIA.
Dr. Senthil Venkatachalam, Department
of Pharmaceutics, JSS College of
Pharmacy, JSS Academy of Higher
Education and Research, Ooty, Nilgiris,
Tamil Nadu, INDIA.
Ms. Anushma Chorsiya, Department of
Pharmacognosy and Phytochemistry,
Delhi Pharmaceutical Sciences and
Research University, New Delhi, Delhi,
INDIA.
Dr.
N
Jawahar,
Department
of
Pharmaceutics, JSS College of Pharmacy,
JSS Academy of Higher Education and
Research, Ooty, Nilgiris, Tamil Nadu,
INDIA.
Cite this article: Namdev B, Senthil V, Jawahar N, Chorsiya A. A Brief Review on Solubility Enhancement Technique:
Hydrotropy. Indian J of Pharmaceutical Education and Research. 2022;56(2):347-55.
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