INTRODUCTION:

Risperidone (Ris) is psychotropic agent used to treat schizophrenia, action of which is mediated through a combination of dopamine Type 2 (D₂) and serotonin Type 2 (5HT₂) receptor antagonism. It is a selective monoaminergic antagonist with high affinity for 5HT₂, D₂ and H1 histaminergic receptors¹. It belongs to chemical class of benzisoxazole derivatives and is 3-[2-[4-(6-fluoro-1, 2-benzisoxazol-3-yl)-1- piperidinyl] ethyl]-6, 7, 8, 9-tetrahydro-2-methyl-4H-pyrido-[1, 2-a]-pyrimidin-4-one with molecular formula of C₂₃H₂₇FN₄O₂ and molecular weight of 410.49 (Fig. 1)

Literature survey revealed that various methods have been reported for estimation of Ris in biological matrices such as plasma with help of LC^{2, 3}, LC with diode array detection⁴, LC with tandem mass spectrometry^5-7and LC with electrochemical detection ⁸. Few stability- indicating methods have been reported for determination of Ris in bulk powder and tablets in presence of its degradation products ^{9, 10.} To the best of knowledge, no spectroscopy method has been developed for the determination of Ris in bulk and tablet dosage forms. Present study involved development of a simple UV spectrophotometric method for the estimation of Ris in bulk and tablet dosage forms.

MATERIALS AND METHOD:

Chemicals and Reagents:

Risperidone (Ris) was obtained as a gift sample from Orchid Pharmaceuticals Ltd., Chennai. All the chemicals used were of analytical grade. The tablet formulations of the three brands were procured from local pharmacy. The declared content of the tablets were ranged from 1mg to 4mg per tablet.

Instrumentation:

Spectroscopic analysis was carried out on a Systronics UV-Visible spectrophotometer – 117 with 1cm matched quartz cells.

Procedure:

Standard stock solution of concentration 100µg/mL was prepared by dissolving accurately weighed 10mg of Ris in 100ml standard flask and the volume was made-up to 100ml with 0.1N HCl. Working standard solution, as prepared above, was scanned in the range of 200-400nm against 0.1N HCl as blank to determine wavelength of maximum absorption (Fig. 2). The plot showed maxima at 238nm.

Preparation of calibration curve:

Aliquots of solution 0.5 – 3mL (100µg/mL) were transferred into a series of 10ml volumetric flask and the volume was made up to 10ml with 0.1N HCl. The absorbance was measured at 238nm, against a reagent blank. Calibration curve was plotted between concentration of Ris and measured absorbance. The data was processed statistically to calculate parameters like coefficient of correlation, linearity, range, slope, intercept, etc. The slope was found to be 0.1794 and -0.1807 was the intercept value obtained from the corresponding calibration graph (Fig. 3). The optical characteristics such as absorption maxima, Beer’s law limits, correlation coefficient, slope, intercept, molar absorptivity and Sand ell’s sensitivity are presented in Table 1.

FIG.1 CHEMICAL STRUCTURE OF RISPERIDONE

TABLE – 1: OPTICAL CHARACTERISTICS AND PRECISION DATA

Parameters	Values
Absorbance maximum (nm)	238
Beer’s law limits (µg/mL)	5-30
Regression equation* (Y) Slope (m) Intercept ( c)	0.9999 0.1794 - 0.1807
Molar absorbitivity (l/mol.cm)	0.1469x10⁵
Sandell’s sensitivity (µg/cm ² /0.001 Absorbance unit)	0.0280
Relative standard deviation (%) **	0.7550
Limit of Detection (µg/mL)	0.72
Limit of Quantification (µg/mL)	2.37

*Y=mX+c, where X= Concentration in µg/mL and Y=Absorbance at the respective λ _max,** Average of six determinations

FIG.2 UV ABSORPTION SPECTRUM OF RISPERIDONE

Preparation of Sample solution:

The marketed tablet formulation of three brands, namely, Respidon(T1) manufactured by Torrent Pharmaceuticals, Risclam(T2) manufactured by Orchid Pharmaceuticals and Risnia (T3) manufactured by Cipla Laboratories, containing 3 mg, 4 mg and 4 mg of Ris respectively procured from local pharmacy were analyzed by the proposed method. Twenty tablets of Ris were accurately weighed and ground to fine powder. Accurately weighed powder equivalent to 10mg of Ris was transferred into a 100ml volumetric flask. Weighed powder was dissolved in 50 mL of 0.1N HCl and shaken for 15 minutes. The solution was filtered through whatmann filter paper no.40 into 100ml volumetric flask and diluted with the same solvent to get the concentration within linearity .The absorbance was measured at 238nm and concentration was determined from regression equation of calibration curve.

Recovery studies:

All the tablet formulations contained excipients and binders, which were added along with the active drug constituents. These substances cause some interference during estimation of the active drug constituents. Interference from the excipients was confirmed by performing the recovery experiments for which standard addition method was employed. So in order to ensure the accuracy and reproducibility of the results obtained, recovery studies were carried out by the addition of known amount of standard drug solution of Ris to pre-analyzed tablet sample solution at three different concentration levels within the range of linearity. The resulting mixtures were analyzed by the proposed method. The statistical data obtained for the determination of Ris in tablet formulation by the proposed method is shown in Table 2.

RESULTS AND DISCUSSION:

The development of a new dosage form involves a number of stages and the analytical methods that are specific, accurate and precise plays a vital role in many of the essential features required for an identical analytical system. Taking in to account the above, an accurate economical and rapid spectrophotometric method was developed for quantitative estimation of Ris in bulk and tablet dosage forms. The linearity range of Ris was determined in 0.1N HCl and found to be 5-30 µg/ml. Commercial formulation (tablets) containing Ris was successfully analyzed by the proposed method. S.D values were low that indicated reproducibility of the proposed method. As an additional demonstration of accuracy, recovery experiments were also performed by adding known amount of pure drug to previously analyzed pharmaceutical preparations and the mixtures were re-analyzed by the proposed method. The results are summarized in Table 2.The percentage of drug recovered (99-101%) was in good agreement with the added amount and labeled claim indicating reproducibility of the methods. Other pharmaceutical additives and excipients usually present in the pharmaceutical dosage form did not interfere with the proposed analytical method.

CONCLUSION:

The applicability of the proposed method for the assay of pharmaceutical preparations was examined. The results of recovery studies performed at three different levels showed high degree of reproducibility and precision of the methods. Also SD calculated was low, indicating the suitability of the proposed method for the routine examination of tablet dosage forms with good precision, sensitivity and accuracy.

TABLE – 2: ANALYSIS OF RISPERIDONE IN TABLET FORMULATION

S. No

Pharmaceutical dosage form (Tablets)^a

Labeled Amount

(mg/tablet)

% Label

Claim Estimated ^b

Percent Recovery ^c

S.D.

99.26

99.32

99.04

99.66

100.1

99.89

0.487

0.559

0.240

^aT1, T2, T3 are tablets from different manufacturers. ^b Average of five determinations. ^cAverage of recovery studies at three different concentration levels. S.D. =Standard Deviation

FIG.3 CALIBRATION CURVE OF RISPERIDONE

ACKNOWLEDGMENTS:

The authors are thankful to Orchid Pharmaceuticals, Chennai for providing the gift sample of Risperidone; and the Principal, Hindu College of Pharmacy, for providing the necessary facilities to carry out the research work.

REFERENCES:

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Received on 15.10.2009 Modified on 10.12.2009

Asian J. Research Chem. 3(1): Jan.-Mar. 2010; Page 151-153