INTRODUCTION:

Methocarbamol, a carbamate derivative of guaifenesin, and is chemically known as 3-(2-methoxyphenoxy)-l, 2-propanediol 1-carbamate¹ shown in Figure 1, is a central nervous system (CNS) depressant with sedative and musculoskeletal relaxant properties. Orally it has been used in reflex muscle spasms and chronic neurologic diseases. Gastric irritation and sedation are the most important side effects.²

Figure 1: Molecular structure of Methocarbamol

Methocarbamol mainly acts as agonist of the GABA_A receptor by the mechanism of activation of the GABA receptor which increases the amount of chloride ions that pass through the chloride channel of cells, resulting in a depressant effect by reducing the cells action potential.

Review literature reveals that several methods have been reported using various instrumental techniques like LC-API-MS method, HPLC method, UV spectrophotometric method, simultaneous estimation method in bulk and pharmaceutical dosage forms and also in biological fluids ^3-11. Up to the best of our knowledge all these reported methods were time consuming, costly (LC-API-MS, HPLC) and requires skilled operator. Hence attempts have been made to develop and validate simple and sensitive Ultra Violet spectrophotometric analytical method for the estimation of Methocarbamol in bulk and pharmaceutical preparation (Tablets) by employing simple UV-Spectrophotometric method.

Literature reports that methocarbamol is sparingly soluble in water and chloroform, soluble in alcohol and propylene glycol, and insoluble in benzene and n-hexane.

MATERIALS AND METHODS:

Instruments:

SYSTRONICS double beam UV-visible spectrophotometer (model 2202) with 1 cm matched quartz cuvettes were used for all absorbance measurements. Shimadzu AUX220 balance was used for weighing the samples accurately.

Materials:

Methocarbamol working reference standard was obtained as a gift sample from Hetero drugs ltd, Hyderabad, India. Methocarbamol USP tablets® were purchased from local pharmacy. AR grade chemicals were procured and used. Acetone and Sodium hydroxide were procured from Merck limited Mumbai. Double distilled water was used throughout the experimental work.

Scanning and determination of λmax:

In order to establish the wavelength of maximum absorption (λ max) of the methocarbamol drug, solution of the drug was prepared in acetone and 0.1N sodium hydroxide solution (1:9) in which the drug is completely soluble and scanned using UV spectrophotometer within the wavelength region of 200-400 nm against 0.1N sodium hydroxide solution as blank ¹³. The drug has an absorption maximum at 267nm (Figure 2) and obeys Beer-Lambert’s law in the concentration range of 5– 25µg mL-¹.

Figure 2: Spectrum of methocarbamol at 200-400 nm

Preparation of standard stock solutions:

A stock solution of Methocarbamol (1mg/ml) was prepared by accurately weighing 100mg of Methocarbamol and dissolved in 10 ml of acetone and make up to 100 ml using 0.1N sodium hydroxide solution (1:9). Aliquots of the standard stock solutions were transferred using A-grade bulb pipettes into 100ml volumetric flasks and solutions were made up to volume with solvent to give a final concentrations of 5-25µg/ml. The absorbance of each solution was measured at 267nm in UV-VIS double beam spectrophotometer (Figure 3). The calibration curve (Figure 4) was then prepared by plotting the absorbance versus concentration of the drug.

Figure 3: Overlain UV spectra of Methocarbamol

Figure 4: Calibration curve of Methocarbamol

Estimation of Methocarbamol in Tablet Formulation:

Twenty tablets of marketed formulation were accurately weighed and finely powdered. An accurately weighed tablet powder equivalent to 100 mg of Methocarbamol was transferred in to 100 mL volumetric flask and then 10 mL Acetone was added, after that 90 ml of 0.1 N sodium hydroxide i.e., 1:9 ratio was added. The volumetric flasks content was sonicated for 15 min. 10mL of above solution was diluted up to 100 mL with 0.1 N sodium hydroxide solution to obtain the concentration of 100 mg/mL of Methocarbamol. 10mL of above solution was diluted up to 100 mL with 0.1 N sodium hydroxide solution to obtain the final concentration of 10 mg/mL of Methocarbamol. The absorbance of final solutions was measured at 267 nm against solvent blank. The readings were taken in replicate and performing the same experiment for dosage forms with different batches.

RESULTS AND DISCUSSION:

Screening of various solvents was made by using a numeral of trials to come across the most advantageous solvent system for dissolving the drug methocarbamol. The drug was found to be more soluble and showed maximum absorbance when Acetone (AR Grade) and 0.1 N Sodium hydroxide solution (AR Grade) in the ratio of 1: 9 used as primary solvent system and further dilutions by 0.1 N Sodium hydroxide solution (AR Grade) by co-solubilization technique. The λmax was found to be 267 nm. Based on the solubility studies and UV spectral data of the methocarbamol drug, combination of those solvents was selected as solvent system as those are easily available and used for the point of time saving.The calibration curve was constructed with concentrations of 5, 10, 15, 20 and 25μg/ml. The linearity was evaluated by linear regression analysis, which was calculated by the least square regression method. The correlation coefficient value was found to be 0.999. The proposed procedure was applied to the determination of Methocarbamol in commercially available tablets. The results obtained were satisfactory and in good agreement as per the ICH guidelines ¹².

Table 1: Method validation data for the proposed method

S.No	PARAMETER	VALUE
1	Linearity Range	5-25 μg/ml
2	Correlation Coefficient	0.999
3	Regression Equation	Y= 0.33x+0.054
4	Slope(m)	0.033
5	Intercept(c)	0.054
6	Molar Absorptivity	9215.368 L mol-¹cm-¹
7	Precision ( % RSD )	0.23
	Interday precision	0.47
	Intraday precision	0.31
	Analyst to Analyst precision	0.47
8	Accuracy	99.31
9	Limit Of Detection	0.121106 µg/ml.
10	Limit Of Quantitation	0.36698 µg/ml.
11	Robustness	0.18

CONCLUSION:

The reported UV Spectrophotometric method was proved to be simple, rapid and reproducible. The validation data indicate good precision, accuracy and reliability of the method. The developed method offers several advantages in terms of simplicity in solvent and time saving which makes the method specific and reliable for its intended use in the determination of Methocarbamol in tablet dosage forms. This method can be of use and value for the quality control division of pharmaceutical companies manufacturing these formulations without any interference.

ACKNOWLEDGEMENT:

The authors acknowledge sincere gratefulness towards the institution VIPS, Kadapa for providing necessary facilities for completion of this project and also Hetero Pharma Ltd., Hyderabad for providing gift sample of standard drug methocarbamol.

REFERENCES:

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9. Nouruddin Wageih Ali, Maha Ahamd Hegazy, Mohamed Abdelkawy, Eglal Abdelahamid Abdelaleem. Simultaneous determination of Methocarbamol and Ibuprofen or Diclofenac potassium using mean centering of the ratio spectra method. Acta Pharmaceutica. 62(2); 2012:191-200.

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Received on 11.06.2014 Modified on 22.06.2014

Research J. Pharm. and Tech. 7(8): August 2014 Page 837-839