Hydrotropy: A Boon in Thin layer Chromatography A Review

Vaishali C. Kulkarni*¹, Manisha D. Khemnar¹, Amruta C. Menkudale¹, Dr. Rupesh J. Patil², Dr. Kishor V. Otari¹

¹Navsahyadri Insititute of Pharmacy, Naigaon, Nasrapur, Pune, 412213.

²Navsahyadri Group of Institutes – Faculty of Engineering, Naigaon, Nasrapur, Pune, .412213.

*Corresponding Author E-mail: vaishalikulkarni115@gmail.com

ABSTRACT:

Around a century ago, in 1916, the term ‘hydrotropy’ was coined by the scientist Carl A. Neuberg to concentrate on anionic organic salts which significantly enhanced the aqueous solubility of weakly soluble solutes¹. The thin layer chromatography (TLC) of drugs are usually performed with the help of solvents like butyl amine, toluene, ether, chloroform, light petroleum, ethyl acetate, ethanol, hexane, xylene and phenol. The majority of which are much expensive and toxic^1-3. Now a days, aqueous solubility of drugs is major problem in pharmaceutical field. Hydrotropic agents are employed as mobile phase for estimation of poorly aqueous soluble drugs by TLC technique. The current review takes the readers throughout a brief summary, geometrical Features of hydrotropic agents, and their different advances toward Chromatographic techniques. Moreover, this review would provide an insight of the future perspectives concerned with the TLC and hydrotropism. In future, hydrotropic solutions shall prove a boon in TLC and high performance thin layer chromatography (HPTLC) analysis of a vast number of drugs thereby limiting the use of organic solvents to a great extent.

KEYWORDS: TLC, HPTLC, Hydrotropy, Hydrotropes, Hydrotropism.

INTRODUCTION:

Hydrotropy refers to the ability of a concentrated solution of a chemical compound to increase the aqueous solubility of an added compound (usually a poorly water-soluble compound). Compounds that have this property are called ‘hydrotropes’. A large number of hydrotropic agents have been reported to enhance the aqueous solubility’s of vast variety of poorly water soluble drugs. When we see the Indian Pharmacopeia and US Pharmacopeia more than one-third of the drugs listed that fall into the poorly water-soluble or water-insoluble categories⁴.

It was also reported that more than 41% of the failures in new drug development have been recognized to poor biopharmaceutical properties, including water insolubility. Most of the newly developed drug molecules are lipophilic in nature and poor solubility is one of the most difficult problems of these drugs. Drug analysis in pure or final product is also important step. Various organic solvents such as methanol, chloroform, dimethyl formamide and acetonitrile have been employed for solubilization of poorly water-soluble drugs to carry out analysis of poorly water-soluble drugs. The drawback of these organic solvents includes high cost, volatility, pollution and toxicity such as nephrotoxicity or teratogenicity, organic solvents are harmful if swallowed, inhaled or absorbed through the skin. Also, as per I.C.H guideline Q3 CR6 (impurities guideline for residual solvents)⁵, these solvents come under the category of Class 2 solvent i.e. solvents which are in limited use. So, there is an urgent need to replace organic solvent with safe eco-friendly, cost-effective solvent for chromatography techniques. Hydrotropic solubilization concept may be a proper choice to preclude the use of organic solvents. Many analytical methods based on hydrotropic solubilization are available in literature and this review focus on the used hydrotropic agent in TLC.

Advantages of Hydrotropic Solubilization:³

· Hydrotropy is recommended to be better to other solubilization methods, such as micellar solubilization, miscibility, co-solvency and salting in, as the solvent character is independent of pH, has high selectivity and does not require emulsification.

· It only requires mixing the drug with the hydrotrope in water.

· It does not require chemical modification of hydrophobic drugs,

· Use of organic solvents, or preparation of emulsion system.

· Economic, safe, environmental friendly and user friendly method.

Features of hydrotropes:⁴

1. Extraordinary solubilization increase.

2. Very high selectivity

3. Easy recovery of solute from solution.

4. Economical and cost effective.

5. Absence of emulsion.

6. Lack of hazards present in additional solvents used in extractive separation.

Properties of hydrotropes⁴

1. Hydrotropes in general are water-soluble and surface-active compounds that can significantly enhance the solubility of organic solutes such as esters, alcohols, aldehydes, ketones, hydrocarbons, and fats.

2. All are non reactive and nontoxic and do not produce any temperature effect when dissolved in water.

3. The solvent character being independent of pH, high selectivity, and the absence of emulsification are the other properties of Hydrotropes.

Significance of hydrotropes⁶:

1. Hydrotropes have been used to solublize organic compounds, dyes, drugs, and bio-chemicals.

2. Hydrotropes have been tested in the development of extractive separation processes in the separation of proteins and in distillation as an extractive solvent for separation of close boiling-point phenolic mixtures.

3. Aqueous hydrotrope solutions offer safe and helpful media for the extraction of natural products and for conducting organic synthetic reactions.

4. Hydrotropes find wide applications in, detergent formulation, health care, and household purposes.

5. They have been used to enhance the rate of heterogeneous reactions.

6. They are used as an extraction agent for fragrances.

7. Also they are used as a fillers and extenders in chemical formulations.

8. In the development of pharmaceutical formulations.

9. Hydrotropic solubilization in nanotechnology (by controlled precipitation).

10. Hydrotropy to give rapid release of weakly water-soluble drugs from the suppositories.

11. Used in the preparation of drilling well fluids and the separation of water-oil emulsion.

12. It may used in the petroleum industry, in tertiary petroleum recovery as well as in other processes.

13. Hydrotropes change the viscosity of surfactant formulations and increase the cloud point of detergents.

14. Aqueous hydrotrope solutions provide safe and useful media for the extraction of natural products and for conducting organic synthetic reactions.

15. Viscosity and cloud point (the temperature at which a clear product begins to become unclear upon cooling) of liquid detergents can be controlled by incorporating hydrotrope agents.

16. Hydrotropes pick up the stability of the concentrated liquid detergents by enhancing the solubility of the surfactants and by regulating the gelling tendency which liquid detergents can exhibit upon dilution with water.

17. This process may be used to recover the solute in crystalline form at an improved purity, and the remaining mother liquor could be used to concentrate the hydrotrope for recycling.

18. Hydrotropes have been useful in, shampoos, degreasing compounds and printing pastes, as an additive for glues used in the leather industry.

19. The use of hydrotrope, sodium xylene sulfonate in paper pulp manufacturing industry gives excellent results.

Mixed hydrotropy:⁶

Mixed hydrotropic solubilization technique is the phenomenon to increase the solubility of weakly water soluble drugs in the bend of hydrotropic agents, which may give unique increase in solubility of poorly water soluble drugs. Use of it in the formulation of dosage forms of water insoluble drugs and to reduce concentration of individual hydrotropic agent to minimize the side effect. i.e. in place of using a large concentration of one hydrotropic a blend of say, 5 hydrotropism can be used as 1/5th concentration reducing their individual toxicities.

Advantages of mixed hydrotropic Solubilization:

1. It reduces the big concentration of individual hydrotropic agents necessary to increase the solubility by employing mixture of agents in lesser concentration.

2. It is new, simple, cost-effective, safe, accurate, precise and ecological friendly method for the analysis

3. It prevents the use of organic solvents and thus avoids the problem of remaining toxicity, error due to volatility, pollution, cost etc

Appliance of Hydrotropy in TLC:

The present study demonstrates the use of hydrotropy for chromatographic estimation of selected model drugs. Hydrotropic agents are working as mobile phase for estimation of poorly aqueous soluble drugs by TLC technique.

1) TLC study of antibiotics:²

The application of hydrotropy for TLC study of antibiotics was carried out by Jayronia et. al. 2013. They perform evaluation of antibiotics such as Erythromycin, Ciprofloxacin and Norfloxacin are selected as model drugs for estimation of this drug by TLC. Solution such as Urea, Sodium Benzoate and Sodium Salicylate were selected as hydrotropic agent for mobile phase. TLC of selected model drugs were also performed by using proposed method as per the method given in Indian Pharmacopoeia (IP).

Table 1: Results study of Thin Layer Chromatography

Sr.No	Drug	Mobile phase used	RF Values
1	Erythromycin	2M urea solution, 2M sodium benzoate solution	0.9, 0.93
2	Ciprofloxacin	2Msodium benzoate solution, 2M sodium salicylate solution	0.53, 0.69
3	Norfloxacin	2M urea solution, 2M sodium benzoate solution	0.81, 0.90

TLC study of NSAID⁷:

Application of hydrotropy in TLC study of NSAID Was carried out by Maheshwari et. al. 2010. They investigate the used hydrotropic solutions as mobile phase to perform TLC of poorly water-soluble NSAIDs, B-blocker, and CNS stimulants drugs precluding the use of organic solvents. Atenolol, Paracetamol, Ibuprofen, Diclofenac sodium & Caffeine were selected as model poorly water-soluble drugs. Substance such as urea & sodium benzoate were used as model hydrotropic agents. TLC of these selected poorly water-soluble drugs was performed using mobile phases as per the Indian Pharmacopoeia (IP) 2007 involving the use of organic solvents.

Table 2: Results study of Thin Layer Chromatography

Sr. No	Drug	Mobile phase used	RF Values
1	Diclofenac Sodium	5M urea solution, 2M sodium benzoate solution	0.87, 0.64
2	Paracetamol	5M urea solution, 0.5M sodium benzoate solution	0.86, 0.68
3	Ibuprofen	5M urea solution, 2M sodium benzoate solution	0.90, 0.82
4	Atenolol	5M urea solution, 1M sodium benzoate solution	0.77, 0.63
5	caffeine	5M urea solution, 2M sodium benzoate solution	0.89, 0.87

3) TLC study of Dyes:⁸

In the research by Salunke et. al. 2019 used hydrotropic solution to separate Dyes by mixed hydrotropy TLC tequniques. Solubility of dyes checked in various hydrotropes. Some single and mixed hydrotropes enhances water solubility of Bromocresol green and phenol red. By trial error basis 20% Niacinamide, 25% niacinamide, 20% sodium benzoate, mixture of 10% sodium citrate and 10% urea was selected for solubilization of dyes. Bromocresol green (triarylmethane dye) and phenol red (phenol sulphonphthalein) slightly water soluble and soluble in organic solvents like as ethanol, dichloromethane and benzene. Organic solvent are toxic in nature, carcinogenic and causes environment pollution.

Table 3: Results Study of Thin Layer Chromatography

Sr.No	Dyes	Mobile phase used	RF Values
1	Bromocresol green	10% Sodium citrate + 10% Urea solution	0.66
2	Phenol red	10% Sodium citrate + 10% Urea solution	0.79
3	Mix of Bromocresol green and phenol red	10% Sodium citrate + 10% Urea solution	0.51 and 0.82

Table 4: Results Study of Thin Layer Chromatography

Sr. No	Drug	Mobile phase used	RF Values
1	Omeprazole	5M Sodium Salicylate solution	0.69

Some other Application:¹⁰

1. Used in Solubility Enhancement.

2. Quantitative estimations of poorly water-soluble drugs by UV-Visible Spectrophotometric analysis, titrimetric analysis precluding the use of organic solvents.

3. Used to enhance the Permeation.

4. Used in Preparations of dry syrups of poorly water-soluble drugs.

5. Used for extraction.

6. Preparation of Injection of poorly water soluble drugs.

7. Used in suppositories for fast release of poorly water –soluble drugs.

CONCLUSION:

It was concluded that the estimated methods of thin layer Chromatography by using hydrotropic solutions was new, simple, cost-effective, environment-friendly and secure. The decided used of organic solvents were prohibited, because of the expense of accuracy. The used of hydrotropic agent can be successfully employed in the TLC of other drugs, as well as It is expected that the hydrotropic solution systems can be employed in HPTLC analysis in future and can be developed as a novel tool to eliminate the use of costly, pollutant and toxic organic solvents.

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Received on 20.12.2019 Modified on 31.01.2020

Asian J. Pharm. Ana. 2020; 10(1):40-43.

DOI: 10.5958/2231-5675.2020.00009.5