Visible Spectrophotometric Determination Of Risperidone In Tablet Formulations

A. Goyal * and I. Singhvi **

*  B. N. P.G. College of Pharmacy, Udaipur (Raj.) 313002

** Department of Pharmaceutical Sciences,  M. L. Sukhadia University,
Udaipur (Raj.) 313001

* For Correspondence

Mailing address: 277,Sector 11, Hiran Magri, Udaipur(Raj.),313001.Telephone
No.: 02942584851, mobile: 09828135201.

E-mail-goyalanjugoyal@yahoo.com

Abstract:

Three simple, economical, precise, convenient and reproducible visible spectrophotometric
methods have been developed for the estimation of risperidone in tablet formulation.
The developed methods are based on the formation of chloroform extractable complex
of risperidone with bromophenol blue, bromothymol blue and bromocresol green
in acidic medium, which shows absorbance maxima at 412.0 nm, 413.0 nm and 414.0
nm respectively. For all three methods linearity was observed in the concentration
range of 5-30 μg/ml of drug. Results of analysis for all the methods were
validated statistically and by recovery studies.

Key Words: Risperidone,Visible Spectrophotometry, Tablet Formulation.

Introduction:

Risperidone, chemically 3-[2-[4-(6-fluro-1,2-benzisoxazol-3-yl) - 1-piperidinyl ] ethyl ]-6,7,8,9- tetra hydro –2-methyl-4H-pyridol[1,2-a] pyrimidin-4-one¹ is an  antipsychotic agent ², which acts through selective antagonism  of serotonin 5HT₂, dopamine D2 receptors, used in the treatment of schizophrenia and other psychoses³. Two HPLC^4-5 methods and one LC-EC⁶ (liquid chromatography with electrochemical detection) for estimation of risperidone from human plasma have been reported in the literature but no analytical method has been developed for the determination of risperidone in tablet dosage form.

The objective of the present investigations was to develop simple,
accurate and economical spectrophotometric methods for estimation of risperidone
in tablet formulation.

Materials and Methods:

Instrument:  Thermospectronic UV1, UV/VIS double beam spectrophotometer with spectral bandwidth of 2 nm, wavelength accuracy of  ± 0.5 and 1 cm matched quartz cells were used for analytical method development.

All the chemicals and reagents used were of analytical grade. Double distilled
water was used for preparation of acid phthalate buffer of pH 4. Bromophenol
blue (0.3%w/v), bromothymol blue (0.3%w/v) and bromocresol green (0.3%w/v) reagents
were prepared in buffer of pH 4. All the three reagents were extracted several
times with chloroform so as to remove chloroform soluble impurities.

Preparation of standard stock solution:

Risperidone (50 mg) was weighed accurately and transferred into a 50 ml volumetric flask. Drug was dissolved and volume made up with chloroform so as to obtain a stock solution of 1mg/ml. This stock solution was further diluted with chloroform to obtain the working standard solution of concentration 100 µg/ml. Aliquots of standard risperidone solution (100 µg/ml) ranging from 0.5-3.0 ml were transferred into a series of 10 ml volumetric flasks and volume made to the mark with chloroform. To 10ml of each dilution taken in a separating funnel, 10 ml of bromophenol blue (method I) reagent bromothymol blue (method II) or bromocresol green (method III) was added. Reaction mixture was shaken gently for 5 minutes, aqueous and chloroform layer was separated out and absorbance of chloroform layer was measured at 412.0 nm, 413.0 nm and 414.0 nm respectively. Prepared respective calibration curve.

Twenty tablets (each 1 mg and 3 mg) were weighed accurately and finely powdered. An accurately weighed portion of each powdered sample, equivalent to 10 mg of risperidone was taken in a 100 ml volumetric flask containing 30 ml of chloroform, sonicated for 20 minutes. The resultant was filtered through whatman filter paper no. 41 into another 100 ml volumetric flask. The filter paper was washed several times with chloroform. The washings were added to the filtrate and the final volume was made up to the mark with chloroform. Ten milliliters of filtrate was further diluted to 100 ml with chloroform. Ten milliliters of each of the final dilution was taken in separating funnel and treated as per procedure described for the preparation of calibration curve. Absorbance was measured at their respective absorbance maxima and concentration of drug in sample solution was determined using calibration curve. Results of analysis are reported in Table 1.

Recovery studies were carried out by the addition of known amount of standard drug solution of risperidone to pre-analyzed tablet sample. The resulting solutions were analyzed by proposed methods. The results of recovery studies were found to be satisfactory and are reported in Table 1.

These proposed methods were found to be simple, accurate, economical and rapid. Recovery studies were found close to 100 percent that indicates accuracy and precision of the proposed methods. Statistical analysis was carried out and the results of which were satisfactory. Standard deviation and relative standard deviation values were low that indicated reproducibility of the proposed methods. It was observed that excipients did not interfere in the determination of risperidone.  Hence these developed methods could be used for routine estimation of risperidone in its tablet dosage forms.

Acknowledgement:

 The authors are thankful to Intas Labs Pvt. Ltd., Ahmedabad, for providing gift sample of risperidone.

Rerences:

1)      Budavari, S., Eds., In; The Merck
Index, Merck & Co., Inc., Whitehouse Station, 13^th ed.,  
2001,1478.

2)      British Pharmacopoeia, Vol.I, 4th   Edn., 2002, 1, 1500. 

3)      Hardman, G., Limbid, L.E. and Gilman, A.G., The Pharmacolgical Basis of Therapeutics, McGraw Hill, 10^th Edn.,  2001, 279.

4)       Avenoso, A., J. chromatogr.,  2000, 173, B-746.

5)      Kapur, S., Langlois, X.  et al, J. PET, 2002, 302,1129-34.

6)      Apseloff, G., Gerber, N. et al, Br. J. of Clin. Pharmacology, 2000, 49, 5.

Table 1  Result of Analysis and Recovery Studies

 * Average of three determinations

** Average of recovery studies at three different concentration
levels