Utilization of Hydrotropic Solubilisation Technique for Quantitative Studies of Dexamethasone in Pharmaceutical preparations

 

Santosh Karajgi*, Sameersing Hajeri, Shripad Potadar

Department of Pharmaceutical Qualtiy Assurance, BLDEA’s SSM College of Pharmacy and Research Centre, Vijayapur 586103, Karnataka.

 

ABSTRACT:

Solubility is a crucial characteristic for achieving the appropriate drug concentration in the systemic circulation and demonstrating pharmacological response. Poor water solubility can severely limit drug efficacy, and some medications can even cause negative effects as a result of their poor solubility. Enhancing water solubility can be done through several of methods. Increased water solubility can thus be a beneficial technique for enhancing therapeutic effectiveness and/or reducing side effects. This is true for solutions that are given intravenously, topically, or orally. Increasing the aqueous solubility of drugs that are weakly water soluble can be done in a variety of techniques. Hydrotropy is a solubility enhancement technique that uses hydrotropes such as sodium benzoate, sodium salicylate, sodium citrate, urea, ibuprofen sodium, and niacin amide to improve the solubility of poorly water-soluble drugs. Hydrotropic solubilization was employed in this study to solubilize weakly water-soluble drug like Dexamethasone utilizing hydrotropic agents like sodium benzoate (2M) and sodium salicylate (2M). Dexamethasone has maximum absorbance at 272.05nm, when sodium benzoate is used as a hydrotropic agent. In the 5-25 µg/ml concentration range, this substance follows the beers law. Dexamethasone shows maximum absorbance at 317.10nm, when sodium salicylate is used as a hydrotropic agent. In the concentrations ranging from 5 to 25µg/ml, this substance follows the beers law. The findings of studies have been statistically confirmed, as well as by re-examination studies. According to the ICH guidelines, validation parameters such as linearity, range, and assay were investigated.

 

 

INTRODUCTION:

Dexamethasone is poorly water-soluble drug and a fluorinated corticosteroid used to treat a variety of disorders including endocrine, rheumatic, dermatologic, allergy, ophthalmic, gastrointestinal, pulmonary, and others.

 

Dexamethasone:

It is physically comparable to other corticosteroids such as [hydrocortisone] and [prednisolone], which it was developed in 1957.¹ The therapeutic effectiveness of a medicine is determined by its bioavailability and, eventually, its solubility. Solubility is a crucial characteristic for achieving the appropriate drug concentration in the systemic circulation and demonstrating pharmacological response.² Hydrotropic is a solubilization process in which a significant amount of a second solute increases the previous solute's water solubility. Many poorly water-soluble drugs have been observed to benefit from concentrated aqueous hydrotropic solutions of sodium benzoate, sodium salicylate, urea, nicotinamide, sodium citrate, and sodium acetate.³ In this current study, an effort is made to improve the aqueous solubility of the selected drug Dexamethasone utilizing hydrotropic agents like sodium benzoate (2M) and sodium salicylate (2M), as there is no reported method is available so far to enhance water solubility and establish linearity of selected drug molecule by hydrotropic solubilisation technique. Dexamethasone is poorly water-soluble medication that can be hydro-tropically dissolved. Many solubility enhancement techniques have been published, and one of the most important is the hydrotropic Solubilisation technique.^4-17

 

MATERIALS AND METHODS:

Materials:

The study was carried out by using Shimadzu UV spectrophotometer Spectronic model 1800 with 1cm matched quartz sample cells. Sodium benzoate, sodium salicylate, urea, sodium acetate, sodium salicylate, and sodium citrate were utilised as reagents. The research was done on commercially available Dexamethasone formulation.

 

Methodology:

First step in this process is to identify the solubilizing agent, which may be sodium benzoate, sodium salicylate, sodium citrate, sodium acetate, and urea. The drug Dexamethasone was dissolved in the second solutes Sodium benzoate and Sodium salicylate using a trial-and-error process.

 

Thus, to increase the aqueous solubility of Dexamethasone, sodium benzoate (2M) and sodium salicylate (2M) both hydrotropic agents are used as solubilizing agents throughout the work. This drug is not soluble in any of the remaining hydrotropic agents (sodium acetate, sodium citrate, and urea).

 

Procedure:

A.    The first trial begins with a solubility test of the drug in a 1 M solution of the solubilizing agent in distilled water, performed in the order of preference. If complete solubility is achieved, no additional solubility tests are necessary.

 

B.    If the chemicals under test are insoluble in either the dilution or treatment mediums, go to trial 2 by adding a significant amount of medium (about 2 M) to try to dissolve the drugs. Further steps are not required if the chemicals under test are dissolved in a medium at a concentration of 2M. Stop attempting to dissolve the chemical if it does not dissolve in one medium or the other. There are no additional solubility tests needed if the drugs are soluble in any of these solvents.

 

C.    If the drug remains insoluble in any of the trial 2 media, move on to trial 3 and change the solubilizing agent. There are no more solubility tests required if the drug is soluble. Table 1 contains the specifics.

 

Validation:

Statistics and re-examination studies have both validated the conclusions of previous investigations. Validation parameters such as linearity, range, and assay were investigated using marketed formulation dexamethasone at 272.05nm, At N=4 when sodium benzoate is used as a hydrotropic agent. Dexamethasone at 317.10nm, At N=3 when sodium salicylate is used as a hydrotropic agent and UV first derivative absorption maximum to establish the testing conditions. The current approach, however, should be revalidated in accordance with ICH or USFDA guidelines. Figure number 1 to 4 and Tables 1–4 features data.^10-11

Table 1: Identification of solubilizing agent

Sl. No.	Drug	Solubilizing Agents	Trails	Concentration	Result
01	Dexamethasone	Sodium citrate	Trail-1	1M	No solubility & precipitation
			Trail-2	2M	No solubility & precipitation
		Sodium acetate	Trail-3	1M	No solubility & precipitation
			Trail-4	2M	No solubility & precipitation
		Urea	Trail-5	1M	No solubility & precipitation
			Trail-6	2M	No solubility & precipitation
		Sodium benzoate	Trail-7	1M	No solubility & precipitation
			Trail-8	2M	Completely soluble
		Sodium salicylate	Trail-9	1M	No solubility & precipitation
			Trail-10	2M	Completely soluble

 

 

Table 2. Linearity Data table and range of Dexamethasone using Sodium Benzoate as hydrotropic agent

Sl. No.	Concentration	Absorbance
01	5µg/ml	2.3
02	10µg/ml	2.0
03	15µg/ml	1.7
04	20µg/ml	1.4
05	25µg/ml	1.1

 

Figure 1. Drug concentration 5 microgram per ml

 

Figure 2. Drug concentration 25 microgram per ml

 

Table 3. Linearity Data table and range of Dexamethasone using Sodium Salicylate as hydrotropic agent

Sl. No.	Concentration	Absorbance
01	5µg/ml	2.2
02	10µg/ml	2.3
03	15µg/ml	2.4
04	20µg/ml	2.5
05	25µg/ml	2.6

 

Figure 3. Drug concentration 5 microgram per ml

 

Figure 4. Drug concentration 25 microgram per ml

Table 4. Comparison Tables of Hydrotropic Agents

Sl No	Solubilizing agents	Drugs	Concentration	Scanning range	Absorption maxima	Assay
01	Sodium Benzoate	Dexamethasone	5-25µg/ml	240-280nm	272.05nm	99.37%
02	Sodium Salicylate	Dexamethasone	5-25µg/ml	300-350nm	317.10nm	101%

 

 

RESULTS:

The solubility of the weakly water-soluble drug Dexamethasone was improved by introducing the second solutes, Sodium benzoate (2M) and Sodium salicylate (2M). Sodium benzoate and sodium salicylate were chosen since the drug is insoluble in other solubilizing agents. Other solubilizing agents used include sodium citrate, sodium acetate, and urea. The drug Dexamethasone is not solubilized in sodium citrate at concentrations of 1M and 2M, and a clear solution is not formed. Similar to sodium citrate, Sodium acetate has been tried at various molarities, but no clear solution has been formed, and the same is true for Urea. However, this medicine is entirely soluble in Sodium benzoate (2M) and Sodium salicylate (2M), and the graph is linear. The rate of solubility increases as the graph becomes more linear.

 

According to ICH guidelines, the developed technique was validated for various parameters such as range, linearity, and assay, with satisfactory results. The objective of this project was to design a quantitative analytical approach for the quantitative estimation of some selected bulk medicine made for cost-effective routine analysis, based on the above results and discussion. The above study is superior since the UV visible spectrophotometer employed is simple to operate and cost effective.

 

Two hydrotropic agents are employed to make drug completely soluble in water; therefore, a comparison of the two hydrotropic agents has been made.

 

DISCUSSION:

Dexamethasone is poorly water-soluble drug. As a result, hydrotropic compounds are utilized to enhance the water solubility of this drug. Sodium benzoate and sodium salicylate are used as hydrotropic agents. In comparison to sodium benzoate, this drug requires less quantity of sodium salicylate to be completely water soluble.

 

In the presence of sodium benzoate as a hydrotropic agent, the drug Dexamethasone scanned in the range of 240-280nm in the concentration range of 5-25g/ml. Dexamethasone was scanned in the same concentration range as in the presence of sodium benzoate when sodium salicylate was used as a hydrotropic agent. However, dexamethasone scanned between 300 and 350 nm.

In the presence of sodium benzoate as a hydrotropic agent, Dexamethasone exhibits decreased absorbance. While Dexamethasone shows increased absorbance in the presence of sodium salicylate as a hydrotropic agent.

 

CONCLUSION:

The newly developed Hydrotropic Solubilization process has been successfully used to improve the solubility of drug that is weakly aqueous soluble Dexamethasone is accurate and exact. To improve the solubility of the first solute, sodium benzoate and sodium salicylate are added as second solutes. Quantitative estimation is carried out by using UV Visible spectrophotometer. Validation parameters like Range, Linearity and Assay are carried out.

 

As the solubility of a drug increases, so does its bioavailability, resulting in an increase in the medicine's efficiency. For a broader area of research, Accuracy, precision, repeatability, and reproducibility are some of the validation parameters that can be used.

 

CONFLICT OF INTEREST:

The Authors have no conflict of interest with this investigation work.

 

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Accepted on 15.02.2022           © RJPT All right reserved

Research J. Pharm. and Tech 2022; 15(12):5785-5788.