INTRODUCTION:

Risperidone (CAS: 106266-06-2) is used to treat schizophrenia, bipolar disorder and irritability associated with autistic disorder^1-2. Risperidone is a crystalline powder with molecular formula C₂₃H₂₇FN₄O₂(Molecular weight 410.49 g/mol). It is chemically 3-[2-[4-(6-fluoro-1,2-benzoxazol-3-yl)-1-piperidinyl] ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2a] pyrimidin-4-one. It blocks dopamine D2 and Serotonin 5-HT2A receptors and thereby stabilizing the mood and reduce the psychotic symptoms. In the present study, the authors have proposed new spectrophotometric techniques for the assay of Risperidone and validated as per ICH guidelines. Literature survey reveals that Risperidone was estimated earlier using spectrophotometry^3-12 by different authors and in the present study, the authors have proposed new spectrophotometric methods for the assay of Resperidone in phosphate buffer (pH 7.0), acetate buffer (pH 4.0) and phosphate buffer (pH 7.5) and the methods were validated as per ICH guidelines.

Figure 1: Chemical structure of Risperidone

MATERIALS AND METHODS:

Shimadzu Model No. UV-1800 double beam UV-VIS spectrophotometer with quartz cells was used for the entire study. Buffer solutions such as phosphate buffer (pH 7.0), acetate buffer (pH 4.0) and phosphate buffer (pH 7.5) were prepared as per IP 2022. Risperidone stock solution was prepared by dissolving 25 mg of Risperidone in methanol (1000 µg/mL) in 25 mL volumetric flask and a series of solutions 1-50 µg/mL were prepared on dilution with acetate buffer (pH 4.0), phosphate buffer (pH 2.0) and phosphate buffer (pH 7.5) for all the three methods as per the requirement. Risperidone is available as tablets with different brand names RISWELI 4 (Wellona Pharma; Label claim: 4 mg), RISNIA MD 1.0Tablets (Cipla; Label claim: 1.0 mg) and RASOMAX 2 (Mitslnnova; Label claim: 2 mg) etc in India.

Method validation

Zero order spectroscopy (D_o)

A series of Risperidone solutions 1-100 µg/mL were prepared from working standard solution on dilution with phosphate buffer (pH 7.0) (Method I), acetate buffer (pH 4.0) (Method II) and phosphate buffer (pH 7.5) (Method III) and scanned (200-400 nm) against their reagent blanks. The absorption spectrum so obtained has shown maximum absorbance (λ_max) at 280 nm for Methods I, II, III and calibration curves were drawn by taking the concentration of the drug solution on the X-axis and the corresponding absorbance on the Y-axis for all the three methods. Precision studies were performed by calculating the percentage relative standard deviation and accuracy studies were carried out by standard addition method.

First order spectroscopy (D₁)

The individual zero-order absorption spectra of Risperidone so obtained were converted into their first-order derivative spectra with the help of inbuilt software of the instrument for all the three methods and the resultant derivative spectrum has shown minima and maxima and therefore the amplitude was chosen for the construction of calibration curves for Method I, Method II and Method III.

Assay of Risperidone tablets

Risperidone is available as tablet dosage forms and 20 tablets of two different brands were procured, weighed, powdered and powder equivalent to 25 mg of Risperidone was accurately weighed and extracted with methanol, sonicated and diluted as per the requirement with phosphate buffer (pH 7.0) (Method I), acetate buffer (pH 4.0) (Method II) and phosphate buffer (pH 7.5) (Method III) and the percentage recovery was calculated as per the regression equations obtained.

RESULTS AND DISCUSSION

New spectrophotometric methods have been developed for the determination of Risperidone in tablets in three different reagents such as phosphate buffer (pH 7.0) (Method I), acetate buffer (pH 4.0) (Method II) and phosphate buffer (pH 7.5) (Method III) solutions.

Table 1: Literature survey

Reagent	λ_max (nm)	Linearity (µg/ml)	Ref.
Potassium dihydrogen phosphate: Acetonitrile: Methanol	280	2-6	3
Methanol	240 and280	20-60	4
Distilled water	450	5.0-40	5
HCl	202	2.5-20	6
HCl	238	2-12	7
Ethanol and Distilled water	550 and 610	4-10	8
Acetone, Dichloromathane, Ethylacetate,Methanol,	414	2-20	9
Methanol and HCl	595.8	10-80	10
Methanol and HCl	280	2-6	11
Hydrotopic solvent	234	10
Phosphate buffer (pH 7.0) Acetate buffer (pH 4.0) Phosphate buffer (pH 7.5)	280	1-50	Present method

Method validation¹³

Zero order spectroscopy (D₀)

Risperidone has shown absorption maxima (λ_max) at 280 nm for Method I, II, III and Beer-Lambert’s law was obeyed over the concentration range 1-50 µg/mL (Table 2) all the three methods and the linear regression equations were found to be y = 0.0269x + 0.0059, y = 0.0246x + 0.0058, y = 0.026x + 0.0121 for phosphate buffer (pH 7.0), acetate buffer (pH 4.0) and phosphate buffer (pH 7.5) respectively.

First order derivative spectroscopy (D₁)

The overlay first-order derivative spectra of Risperidone I phosphate buffer (pH 7.0) (Method I), acetate buffer (pH 4.0) (Method II) and phosphate buffer (pH 7.5) (Method III) were shown in Figure 2. The derivative spectrum has shown maxima at 227.07 nm, 226.45 nm and 227.06 nm for Method I, II, III respectively and a calibration curve was drawn by plotting the concentration of the drug solution on the x-axis and the corresponding derivative absorbance at the maxima on the y-axis. Risperidone obeys Beer-Lambert’s law over the concentration range 1-50 µg/mL for all the three methods (Table 3) and the first derivative absorption spectrum of Risperidone (D₁) was shown in Figure 2.

Method I

Method II

Method III

Figure 2: Overlay first order derivative absorption spectra of Risperidone (D1)

Table 2: Linearity (Zero order spectroscopy)

Conc. (µg/mL)	*Absorbance
Conc. (µg/mL)	Method I	Method II	Method III
1	0.0372	0.0281	0.0277
2	0.0578	0.0498	0.06
5	0.1474	0.1304	0.1662
10	0.2726	0.2511	0.2722
20	0.5526	0.5179	0.5474
30	0.8015	0.7456	0.7809
50	1.3576	1.2284	1.3099

*Mean of three replicates

Table 3: Linearity (First derivative spectroscopy)

Conc. (µg/mL)	Method I	Method II	Method III
Conc. (µg/mL)	Maxima (227.07 nm)	Maxima (226.45 nm)	Minima (227.06 nm)
1	0.001	0.001	0.001
2	0.002	0.003	0.002
5	0.006	0.007	0.005
10	0.011	0.013	0.011
20	0.024	0.026	0.021
30	0.035	0.039	0.031
50	0.057	0.064	0.052

*Mean of three replicates

The percentage RSD in accuracy and precision in all the methods was found to be less than 2.0 indicating that the methods are precise and accurate. The results of precision study were shown in Table 3. The percentage of purity of Risperidone tablets was found to be 99.45-99.55, 99.35-99.70 and 99.30-99.85 in zero order spectroscopy and 99.34-99.58, 99.56-99.69 and 99.34-99.80 in first order derivative spectroscopy. The optical characteristics of the method were shown in Table 4.

Table 3: Precision study (D₀)

Intraday precision
Conc. (µg/mL)		*Absorbance
Conc. (µg/mL)		Method I	Method II	Method III
10		0.2722	0.2511	0.2726
10		0.2737	0.2532	0.2731
10		0.2717	0.2561	0.2789
10		0.2724	0.2530	0.2767
10		0.2756	0.2556	0.2745
10		0.2717	0.2573	0.2776
*Mean ± S.D (% RSD)		0.2728 ± 0.0015 (0.5499)	0.2543 ± 0.0023 (0.9044)	0.2755 ± 0.0025 (0.9074)
Interday precision
Conc. (µg/mL)		*Absorbance
Conc. (µg/mL)		Method I	Method II	Method III
Day 1	10	0.2737	0.2690	0.2640
Day 2	10	0.2711	0.2620	0.2650
Day 3	10	0.2751	0.2630	0.2650
Mean ± S.D (% RSD)		0.2733 ± 0.0020 (0.7318)	0.2647 ± 0.0038 (1.4356)	0.2646 ± 0.0005 (0.1889)
Day 1	20	0.5414	0.5460	0.5450
Day 2	20	0.5486	0.5400	0.5310
Day 3	20	0.5339	0.5490	0.5430
Mean ± S.D (% RSD)		0.5413 ± 0.0074 (1.3671)	0.545 ± 0.0046 (0.844)	0.5396 ± 0.0075 (1.3899)
Day 1	50	1.3534	0.7840	0.8030
Day 2	50	1.3542	0.7830	0.8220
Day 3	50	1.3501	0.8030	0.7990
Mean ± S.D (% RSD)		1.3526 ± 0.0022 (0.1627)	0.79 ± 0.0112 (1.4177)	0.808 ± 0.0122 (1.5099)

*Mean of three replicates

Table 4: Optical characteristics

Parameters	Method I	Method II	Method III
Linearity range (µg/mL)	1-50	1-50	0-50
λ_max(nm)	280	280	280
Molar extinction coefficient (litre/mole/cm^-1)	11.048 × 10³	10.103 × 10³	10.684 × 10²
Sandell’s sensitivity (µg/cm²/0.001 absorbance unit)	0.1821	0.1951	0.4269
Slope	0.0269	0.026	0.0246
Intercept	0.0059	0.0121	0.0058
Correlation coefficient	0.9998	0.9992	0.9996

CONCLUSION:

The proposed and validated spectrophotometric methods are found to be very simple, accurate, precise and economical and can be applied for the analysis of Risperidone Pharmaceutical dosage forms.

ACKNOWLEDGEMENT:

The authors are grateful to Aurobindo Pharma Ltd. for providing the gift samples of Risperidone and M/s GITAM (Deemed to be) University for providing the research facilities.

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Received on 07.01.2025 Revised on 24.03.2025

Accepted on 29.05.2025 Published on 01.07.2025

Available online from July 05, 2025

Research J. Pharmacy and Technology. 2025;18(7):3336-3339.

DOI: 10.52711/0974-360X.2025.00482

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