Solid as solvent- Novel Spectrophotometric Analytical Method for Metronidazole Tablets using Solids (Eutectic Liquid of Phenol and Niacinamide) as Solubilizing Agents (Mixed Solvency Concept)

Rajesh Kumar Maheshwari¹, Masheer Ahmed Khan², Nupur Maheshwari¹, Neelesh Maheshwari³

¹Department of Pharmacy, Shri G S Institute of Technology and Science, Indore (India)

²School of Pharmacy, Devi Ahilya Vishwavidyalaya, Indore

³School of Pharmaceutical Sciences, RGPV, Bhopal

*Corresponding Author E-mail: rkrkmaheshwari@yahoo.co.in

ABSTRACT:

The researchers are doing much work to give eco-friendly solutions for the pollution and toxicity caused by most of the organic solvents. Maheshwari has given a nice concept, known as mixed-solvency concept by the application of which, innumerable solvent systems can be developed. Maheshwari is of the opinion that each substance possesses solubilizing power. He has given several eco-friendly methods in the area of drug estimations and formulations precluding the use of toxic organic solvents. The present research work also provides an eco-friendly method to estimate spectrophotometrically, the metronidazole drug in tablet formulations without the help of organic solvent. The present investigation is an attempt to show that solids can also be wisely used to act as solvent precluding the use of organic solvents. The main objective of the present study is to demonstrate the solvent action of solid. Solid excipients can nicely be employed as solubilizers in the development of pharmaceutical dosage forms in solution form of poorly soluble drugs (mixed solvency concept). Present study describes the application of solvent character of eutectic liquid consisting of phenol and niacinamide in 25:10 ratio (PNM 2510) on the weight basis for spectrophotometric estimation of metronidazole tablets. Solubility of metronidazole in distilled water was found to be 7.28 mg/ml at room temperature. More than 80 mg of metronidazole dissolves in 1 ml of PNM 2510. In the present investigation, PNM 2510 was utilized to extract out (dissolve) the drug from tablet powder of metronidazole tablets. Distilled water was used for dilution purpose. Absorbance was noted at 320 nm against reagent blank to calculate the amount of drug in the tablets. Proposed method is novel, eco-friendly, rapid, free from toxicity of organic solvent, accurate and reproducible. Recovery studies and statistical data proved the accuracy, reproducibility and precision of the proposed method. The presence of phenol, niacinamide and tablet excipients did not interfere in the spectrophotometric estimation of metronidazole at 320 nm. Phenol and niacinamide do not interfere above 300 nm in spectrophotometric analysis.

KEYWORDS: Mixed-solvency concept, metronidazole, phenol, niacinamide, eutectic liquid, spectrophotometric analysis.

INTRODUCTION:

Majority of drugs show the problem of poor solubility, whether in the case of their analytical estimations or in the field of liquid dosage forms in the form of solutions. Commonly used organic solvents for spectrophotometric analysis of water insoluble drugs include methanol, ethanol, chloroform, benzene, dichloromethane, dimethyl formamide, acetonitrile, ethyl acetate, toluene, carbon tetrachloride, acetone, hexane etc. The main drawbacks of organic solvents include high cost, toxicity and pollution. Organic solvents have innumerous adverse effects caused by single exposure like dermatitis, headache, drowsiness, nausea, eye irritation and long term exposure causes serious effects such as neurological disorders, chronic renal failure, liver damage, necrosis, mutagenesis disorder. They should be replaced by other eco-friendly alternative sources. The pollution and toxicity caused by most of the organic solvents is a big challenge. The researchers are doing much work to give eco-friendly solutions for this challenge. Maheshwari^1-5 has given a nice concept, known as mixed-solvency concept. By application of this concept, innumerable solvent systems can be developed. Maheshwari is of the opinion that each substance possesses solubilizing power. He has given several eco-friendly methods in the area of drug estimations and formulations precluding the use of toxic organic solvents. The present research work also provides an eco-friendly method to estimate spectrophotometrically, the metronidazole drug in tablet formulations without the help of organic solvent.

There are very few safe liquids e g propylene glycol, glycerin, tweens, ethanol, liquid polyethylene glycols (like PEG 200, 300 etc) which are employed by pharmaceutical industries in various dosage forms for making solution type dosage forms of poorly soluble drugs. Mixed solvency concept, proposed by Maheshwari^1-3 provides a means to develop innumerable solvent systems employing combination of the pharmaceutical excipients in small concentrations. Each substance present on the earth has got solubilizing power. By combining the excipients, additive solvent actions and synergistic solvent actions can be obtained. The problem of toxicity issue due to high concentration of a single solvent can be solved in this manner. The solubility of a large number of poorly soluble drugs has been enhanced by mixed solvency concept^1-39.

The present investigation is an attempt to show that solids can also be wisely used to act as solvent, precluding the use of organic solvents. In a separate study, author has attempted soxhelation using phenol as solvent. The vapours of boiling phenol got condensed in extraction chamber to effect the extraction of active constituents from powder of crude drugs. The main objective of the present study is to demonstrate the solvent action of solids. Solid excipients can nicely be employed as solubilizers in the development of pharmaceutical dosage forms in solution form of poorly soluble drugs (mixed solvency concept). Present study describes the application of solvent character of eutectic liquid consisting of phenol and niacinamide in 25:10 ratio (PNM 2510) on the weight basis for spectrophotometric estimation of metronidazole tablets. Solubility of metronidazole in distilled water is 7.28 mg/ml at room temperature. More than 80 mg of metronidazole dissolves in 1 ml of PNM 2510. In the present investigation, PNM 2510 was utilized to extract out (dissolve) the drug from tablet powder of metronidazole tablets. Distilled water was used for dilution purpose. Absorbance was noted at 320 nm against reagent blank for determination of drug content. Proposed method is novel, eco-friendly, rapid, free from toxicity of organic solvent, accurate and reproducible. Recovery studies and statistical data proved the accuracy, reproducibility and precision of the proposed method. The presence of phenol, niacinamide and tablet excipients did not interfere in the spectrophotometric estimation of metronidazole at 320 nm. Phenol and niacinamide do not interfere above 300 nm in spectrophotometric analysis.

MATERIALS AND METHODS:

The gift sample of metronidazole bulk drug was a generous gift by M/S Alkem Laboratories Limited, Mumbai (India). Commercial tablets of metronidazole were procured from local market. All other chemicals used were of analytical grade.

A Shimadzu-1700 UV visible spectrophotometer with 1 cm matched silica cells was used for spectrophotometric analysis.

Calibration curve:

Accurately weighed 50 mg of metronidazole standard drug was transferred to a 500 ml volumetric flask. Ten ml of PNM 2510 was added and the flask was shaken to dissolve the drug. Then, about 400 ml of distilled water was added and the flask was shaken for 5 min to solubilize the contents. Then, the volume was made up to 500 ml with distilled water to get a stock solution of 100 µg/ml. The stock solution was suitably diluted with distilled water to prepare standard solutions of 5, 10, 15, 20 and 25 µg/ml. The absorbencies of these standard solutions were noted at 320 nm against respective reagent blanks.

Preliminary solubility studies:

To determine the solubility of the drug in distilled water at room temperature, sufficient excess amount of the drug was added to a 25 ml capacity vial containing distilled water. After putting the vial cap and applying the aluminum seal, the vial was shaken mechanically for 12 hours at room temperature in an orbital flask shaker (Khera Instrument Pvt. Ltd., India).

Table 1. Analysis data of metronidazole tablet formulations with statistical evaluation (n=3)

Tablet formulation	Label claim (mg/tablet)	Percent drug estimated (mean ± SD)	Percent coefficient of variation	Standard error
I	400	98.45 ± 1.397	1.419	0.809
II	400	100.19 ± 1.881	1.877	1.086

Table 2. Results of recovery studies with statistical evaluation (n=3)

Tablet formulation	Drug in pre-analyzed tablet powder (mg)	Amount of standard drug added (mg)	% Recovery estimated (mean ± SD)	Percent coefficient of variation	Standard error
I	50	15	101.33±1.777	1.754	1.026
I	50	30	101.88±0.932	0.915	0.538
II	50	15	100.73±1.248	1.239	0.721
II	50	30	99.91±0.870	0.871	0.502

The solution was allowed to equilibrate for 24 hours undisturbed and then, filtration was done through Whatman filter paper # 41. The filtrate was appropriately diluted with distilled water to measure the absorbance at 320 nm.

In order to determine the approximate solubility of drug in PNM 2510, one ml of PNM 2510 was transferred to a 10 ml volumetric flask. The weight of the stoppered volumetric flask (initial weight) was noted. About 5 mg of drug was added and the flask was shaken to solubilize the drug. As soon as a clear solution was obtained again about 5 mg of drug was added and the flask was shaken to solubilize the drug to get a clear solution. Same process was repeated till the liquid was saturated with drug. Again the weight of volumetric flask was noted (final weight). Difference in these two weights (initial and final) gave the approximate amount of drug which saturates (nearly) one ml of PNM 2510.

Proposed method of analysis:

Twenty tablets of tablet formulation I were weighed and crushed to get a fine powder. Tablet powder equivalent to 50 mg metronidazole was transferred to a 500 ml volumetric flask. Then, 10 ml of PNM 2510 was transferred to it and the flask was shaken vigorously for 10 min by hand shaking to extract (solubilize) the drug from the tablet powder. Then, about 400 ml distilled water was added and the flask was shaken for about 5 min for proper solubilization of phenol, niacinamide and drug in the distilled water. Then, sufficient distilled water was added to make up the volume up to 500 ml. Filtration was carried out through Whatmann filter paper # 41 to remove the insoluble tablet excipients. Then, the absorbance of the filtrate was noted at 320 nm against the reagent blank. The drug content was calculated using the calibration curve. Same procedure was repeated for tablet formulation II. The results of analysis are reported in table 1.

Recovery studies:

In order to validate the proposed analytical method, recovery studies were performed for which standard metronidazole drug was added (15 mg and 30 mg , separately) to the pre-analyzed tablet powder equivalent to 50 mg metronidazole and the drug content was determined by the proposed method. Results of analysis with statistical evaluation are reported in table 2.

RESULTS AND DISCUSSION:

7.28 mg/ml was the observed solubility of metronidazole in distilled water at room temperature. The solubility of metronidazole in PNM 2510 was more than 80 mg per ml of PNM 2510.

It is evident from table 1 that the percent drug estimated in tablet formulation I and II were 98.45±1.397 and 100.19±1.881, respectively. The values are very close to 100.0 indicating the accuracy of the proposed analytical method. Small values of statistical parameters viz. standard deviation, percent coefficient of variation and standard error (table 1) further validated the method. Further, table 2 shows that the range of percent recoveries varied from 99.91±0.870 to 101.88±0.932, which are again very close to 100.0, indicating the accuracy of the proposed method. The accuracy of the proposed analytical method is further supported by significantly small values of statistical parameters viz. standard deviation, percent coefficient of variation and standard error.

CONCLUSION:

The proposed method is new, simple, environment friendly, accurate and reproducible. The proposed method can be successfully employed in the routine analysis of metronidazole tablets. The use of PNM 2510 can also be done to estimate other water insoluble drugs which are estimated above 300 nm. Phenol and niacinamide do not interfere above 300 nm. Obtained accuracy of the proposed analytical method is also indicative of the proof that the solids possess solvent character.

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Received on 12.01.2016 Modified on 16.03.2016

Accepted on 15.04.2016 © RJPT All right reserved

Research J. Pharm. and Tech. 2016; 9(6):705-708

DOI: 10.5958/0974-360X.2016.00132.3