Hydrotropy A Promising Tool For Solubility Enhancementa Review PDF
Hydrotropy A Promising Tool For Solubility Enhancementa Review PDF
Kapadiya Nidhi1, Singhvi Indrajeet1, Mehta Khushboo1, Karwani Gauri1 and Dhrubo Jyoti Sen2
1
Pacific College of Pharmacy, Pacific Hills, Udaipur-313002, Rajasthan, India
2
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Department of Pharmaceutical Chemistry, Shri Sarvajanik Pharmacy College, Gujarat Technological University,
Arvind Baug, Mehsana-384001, Gujarat, India
The study on solubility yields information about al. This is an open access paper distributed under the
the structure and intermolecular forces of drugs. copyright agreement with Serials Publication, which
bioavailability, pharmacological action and reproduction in any medium, provided the original
How to Cite this Paper: whereby addition of large amount of second solute
Kapadiya Nidhi, Singhvi Indrajeet, Mehta results in an increase in the aqueous solubility of
Khushboo, Karwani Gauri and DhruboJyoti another solute. However, the term has been used in
Sen “Hydrotropy: A Promising tool for solubility the literature to designate non-micelle-forming
Enhancement”, Int J. Drug Dev. & Res., April-June substances, either liquids or solids, organic or
parts, an anionic group and a hydrophobic aromatic Table 1: Expression for approximate solubility[4].
ring or ring system. The anionic group is obviously
Relative amounts of solvents to
Descriptive terms
involved in bringing about high aqueous solubility, dissolve 1 part of solute
Very soluble Less than 1
which is a prerequisite for a hydrotropic substance.
Freely soluble From 1-10
The type of anion or metal ion appeared to have a
Soluble From 10-30
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minor effect on the phenomenon[2]. On the other Sparingly soluble From 30-100
hand, planarity of the hydrophobic part has been Slightly soluble From 100-1000
emphasized as an important factor in the mechanism Very slightly soluble From 1000-10,000
of hydrotropic solubilization. Solute consists of alkali Insoluble or practically
More than 10,000
insoluble
metal salts of various organic acids. Hydrotropic
agents are ionic organic salts. Additives or salts that General parameters affecting solubility are particle
increase solubility in given solvent are said to “salt size, shape and surface area physicochemical
in” the solute and those salts that decrease solubility properties of drugs, and physical forms of drugs,
“salt out” the solute. Several salts with large anions or solvents, pH of the medium, temperature and use of
cations that are themselves very soluble in water surfactants[3]. The pharmacopoeia lists solubility in
terms of dissolve 1g of solute. If exact solubilities are
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“hydrotropism”. Hydrotropic solutions do not show terms to describe a given range. These descriptive
colloidal properties and involve a weak interaction terms are listed in (Table 1).
Solubility enhancement of various poorly soluble Therapeutic effectiveness of a drug depends upon the
compounds is a challenging task for researchers and bioavailability and ultimately upon the solubility of
pharmaceutical scientists. Solubility is one of the drug molecules. Solubility is one of the important
concentration of drug in systemic circulation for in systemic circulation for pharmacological response
pharmacological response to be shown[2]. The study to be shown[5]. Due to advanced research &
on solubility yields information about the structure development, there are varieties of new drugs & their
and intermolecular forces of drugs. Drug efficacy can derivatives are available. But more than 40% of
be severely limited by poor aqueous solubility and lipophilic drug candidates fail to reach market due to
some drugs also show side effects due to their poor poor bioavailability, even though these drugs might
solubility. There are many techniques which are used exhibit potential pharmacodynamic activities. The
to enhance the aqueous solubility. The ability to lipophilic drug that reaches market requires a high
increase aqueous solubility can thus be a valuable aid dose to attain proper pharmacological action. The
to increase efficiency and/or reduce side effects for basic aim of the further formulation & development
certain drugs. This is true for parenterally, topically section is to make that drug available at proper site of
solute is in equilibrium with the solvent[7-9]. between the solvent and the solute molecule or ion.
MECHANISM OF HYDROTROPE ACTION[2] It is evident from the literature survey that more is
A hydrotrope is a compound that solubilises the concentration of hydrotrope; more is the aqueous
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Paracetamol, Diclofenac
Urea two steps are used
sodium
Theophylline Sodium salicylate 1) Preparation of saturated solution: Solubility
Ibuprofen sodium, sodium
Salicylic acid indicates the maximum amount of a substance
salicylate
Furesamide Ibuprofen sodium that can be dissolved in a solvent at a given
Chlorpropamide, temperature. Such a solution is called
Ibuprofen sodium
gatifloxacin
nifedipine Sodium salicylate saturated. Solubility is measured either in
ketoprofen Urea, sodium citrate grams per 100 g of solvent (g/100 g) or
Cefadroxil Urea number of moles per 1 L of the solution.
2) Analysis of saturated solution :
Then, again gross weight was noted. From the
Once the saturated solution is prepared its
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room temperature. Enhancement ratios in agents, which may give miraculous synergistic
solubilities were determined by following formula - enhancement effect on solubility of poorly water
Enhancement ratio = Solubility in hydrotropic soluble drugs, utilization of it in the formulation of
solution÷ Solubility in distilled water dosage forms of water insoluble drugs and to reduce
Smita Sharma, Mukesh C. Sharma[25] were concentration of individual hydrotropic agent to
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investigate that hydrotropic solution of 8M urea has minimize the side effects (in place of using a large
been employed as solubilizing agent to solubilization concentration of one hydrotrope a blend of, say, 5
poorly water soluble drug Pseudoephedrine Sulphate, hydrotropes can be employed in 1/5th concentrations
Desloratidine, from fine powder of its tablet dosage reducing their individual toxicities[27]. Veena Nair,
form for spectrophotometric determination in Mithun S Rajput[28] were developed a novel, safe and
ultraviolet region. Pseudoephedrine Sulphate, sensitive method of spectrophotometric estimation in
Desloratidine shows maximum absorbance at the ultraviolet region using a mixed hydrotropic
resulting solutions were measured at 274.4 nm and solution, containing a blend of 30% w/v urea, 13.6%
289.1nm. R. K. Maheshwari, s. R. Bishnoi, d. Kumar, w/v sodium acetate and 11.8% w/v sodium citrate for
murali krishna[26] , in the present investigation, the quantitative determination of ketoprofen, a
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hydrotropic solution of ibuprofen sodium (0.5M) was poorly water soluble drug, in tablet dosage form.
employed as solubilizing agent to solubilize the Beer's law was obeyed in the concentration range of
poorly water-soluble drug, ornidazole from fine 4–20 µg/ml. There was more than 570-fold
powder of its tablets for spectrophotometric enhancement in aqueous solubility of ketoprofen in
determination. Ornidazole shows its maximum mixed hydrotropic solution as compared with the
absorbance at 320 nm and Beer’s law was obeyed in solubility in distilled water precluding the use of
concentration range of 5-25 mcg/ml. organic solvents. Nilesh Jain, Ruchi Jain, Navneet
Thakur, Brahm Prakash Gupta, Jitendra Banweer
ADVANTAGES OF HYDROTROPIC and Surendra Jain[13] were developed
SOLUBILIZATION TECHNIQUE[2] Spectrophotometric method using 2 M sodium
1. Hydrotropy is suggested to be superior to other acetate and 8 M Urea solution as hydrotropic
solubilization method, such as miscibility, solubilizing agent for the quantitative determination
micellar solubilization, co solvency and salting of poorly water‐soluble hydrochlorothiazide in tablet
in, because the solvent character is dosage form. There were more than 55 and 70 fold
independent of pH, has high selectivity and enhancements in the solubility of
does not require emulsification hydrochlorothiazide increases in 2 M sodium acetate
2. It only requires mixing the drug with the and 8 M Urea solution as compared to solubilities in
hydrotrope in water. distilled water. Hydrochlorothiazide shows
3. It does not require chemical modification of maximum absorbance at 272 nm. Sodium acetate
hydrophobic drugs, use of organic solvents, or and urea did not show any absorbance above 240
preparation of emulsion system. nm, and thus no interference in the estimation was
seen. Hydrochlorothiazide is obeyed Beer’s law in the
MIXED HYDROTROPY concentration range of 10 t0 50µg/ml (r2= 0.999) in
Mixed hydrotropic solubilization technique is the sodium acetate and 5 to 25 µg/ml (r2= 0.999) in urea
phenomenon to increase the solubility of poorly with mean recovery 98.74 and 99.99% in sodium
water-soluble drugs in the blends of hydrotropic acetate and urea respectively.
hydrotropes. For example sodium benzoate, urea, their dosage forms by using hydrotropic agent. Int.
sodium salicylate and ibuprofen sodium etc. In J. Appl. Pharma. 2010; 2(3): 1114.
present scenario this method is getting lot of values 14. Sharma R, Pathodiya G, Mishra PG. A novel
application of hydrotropic solubilization
and may be proved the best method in future.
indevelopment and validation of
spectrophotometric method forsimultaneous
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REFERENCES
estimation of paracetamol and diclofenac sodium in
1. Neuberg, C. Hydrotropy. Biochem. Z 1916; 76: 107-
solid dosage form International Journal of Pharma
109.
and Bio Sciences 2010; 1(3): 1-9.
2. Jain P, Goel A, Sharma S, Parmar M. Solubility
15. C J, K D, D N, Gandhi N. Quantitative analysis of
Enhancement Techniques with Special Emphasis
theophylline bulk sample using sodium salicylate
On Hydrotrophy. International Journal of Pharma
hydrotrope. International Journal of Pharmacy
Professional’s Research July 2010; 1(1): 34-45.
and Pharmaceutical Sciences 2010; 2(4): 80-81.
3. Behera AL, Sahoo SK, Patil SV. Enhancement of
16. Maheshwari RK, Chavada V, Varghese S, Shahoo K.
solubility: a pharmaceutical overview. Der
Analysis of bulk sample of salicylic acid by
Pharmacia Lettre 2010; 2(2): 310-318.
application of hydrotropic solubilization
4. Indian Pharmacopoeia, Goverment of India
method.Indian journal pharmaceutical science
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