Quantitative determination of Domperidone and Ranitidine in combined dosage form by FT-IR spectroscopy

Transcription

1 RESEARCH ARTICLE Am. J. PharmTech Res. 2012; 2(4) ISSN: Quantitative determination of Domperidone and Ranitidine in combined dosage form by FT-IR spectroscopy P. Ravi Prasad *1, K. Bhuvaneswari 1, Murarilal 1, K. Rajani 1 1. Analytical Chemistry Division, Indian Institute of Chemical Technology,Hyderabad , India. ABSTRACT A simple and rapid method has been developed for the quantification of Domperidone (DMP) and Ranitidine (RAN) through FT-IR in combined dosage form. The method involves the measurement of peaks of amine (-NH) at 1620 cm -1 (RAN) and carbonyl group (C=O) at 1717 cm -1 (DMP). The method was validated for pharmaceuticals in tablet form and found to be precise with high recovery levels (>99%). Journal home page: Key words: FT-IR, Ranitidine, Domperidone, combined dosage form. *Corresponding Author raviprasad_pandit@rediffmail.com Received 15 May 2012, Accepted 2 June 2012 Please cite this article in press as: Prasad PR et al., Quantitative determination of Domperidone and Ranitidine in combined dosage form by FT-IR spectroscopy. American Journal of PharmTech Research 2012.

2 INTRODUCTION Chemically, Ranitidine (RAN) is N-(2-[(5-(dimethylaminomethyl)furan-2-yl)methylthio]ethyl)- N-methyl- 2-nitroethene- 1,1-diamine. It is a H 2 -receptor antagonist and recommended for the treatment of peptic ulcers. Domperidone (DMP) is chemically 5-chloro-1-[1-{3-(2-oxo-2, 3- dichloro-1h-benzimidazole-1-yl}propyl]-piperidine-4-yl]-1,3-dihydro-2h-benzimidazol-2-one and is used as antiemetic drug. Both the drugs are available in combination with other drugs as combined dosage tablet forms. A combination of RAN (150mg) with DMP (10mg) is available as combined dosage tablet under the trade name RANTAC D for clinical practice. The tablet is used for antiemetic and peptic ulcer disorders. Many methods are available in literature for their determination in pure form [1-9] and their combination with other drugs [10-16]. But methods for their determination in combined dosage forms of RAN and DMP are not available except HPLC [17] and UV-spectroscopic [18] method using Vierodt s formula. An attempt was made to develop a simple, rapid and non-destructive method using FT-IR for the estimation of both these drugs (Figure 1 & Figure 2) in combined dosage tablet forms. Figure 1: RAN Figure 2: DMP MATERIALS AND METHODS Materials FT-IR spectra were recorded on Thermo Nicolet, Model Nexus 670, USA, Spectrophotometer. KBr used for recording spectra was spectroscopic grade obtained from Sigma-Aldrich, Germany. The reference standards of Ranitidine and Domperidone were obtained as gift samples from M/s Dr. Reddy s Laboratory, Hyderabad and M/s Ipca Laboratories Ltd., Madhya Pradesh respectively. Combined dosage form tablets RANTAC D were procured from local market, Hyderabad. Methods Standards preparation and calibration Fused KBr pellete spectra were recorded between 4000cm -1 and 400cm -1, by averaging 32 scans with a resolution of 4cm -1 with a DTGS detector. For calibration, the spectra were recorded by compressing the standard substances RAN & DMP in the concentration range 0.58mg to 1.45mg and 0.04mg to 0.10mg respectively in spectral grade KBr

3 Absorbance (1620cm-1) Absorbance (1717cm-1) A synthetic mixture of pure DMP & RAN was prepared in the ratio 1:15 similar to commercial tablet formulations namely RANTAC D. Calibration was carried out for RAN and DMP in synthetic mixture in the concentration range mentioned for individual drugs. Sample preparation and formulation analysis Ten tablets of RANTAC D were weighed and ground to a fine powder. A known quantity of it equivalent to the concentration of the individual drug in the calibration range was compressed with spectral grade KBr. Five KBr discs of different concentrations were prepared and spectra were recorded for both RAN and DMP under similar experimental conditions as standards. The validation of the developed method was ascertained by carrying out recovery studies and the precision of the method was expressed as %RSD of a series of measurements. RESULTS AND DISCUSSION The FT-IR spectra of pure RAN and DMP by KBr pellete method is given in Figure 5. The compounds exhibited strong sharp signals at 1620cm -1 (RAN) & 1717cm -1 (DMP) which are due to the absorption of amine (-NH) and carbonyl group (C=O) respectively. This feature is taken for the quantitative analysis. A calibration has been carried out for RAN and DMP using known quantities of standards as mentioned in the experimental section. It was found that the compounds followed the linearity in the concentration range studied (0.58mg 1.45mg for RAN and 0.04mg mg for DMP) (Table 1). Linearity plots of concentration vs absorbance of the compounds for RAN and DMP were shown in Figure 3 & Figure Concentration (mg) Concentration (mg) Figure3:Calibration plot of pure RAN Figure 4: Calibration plot of pure DMP 374

4 % T % T a b Wavenumber(cm -1 ) Figure 5: FT-IR Spectra of pure a. DMP and b. RAN a b Wavenumber(cm -1 ) Figure 6: FT-IR Spectra of a. Synthetic Mixture b. RANTAC D Table 1: Optical characteristics Parameters Ranitidine Domperidone Beer s Law Limit mg mg Limit of detection 0.001mg 0.001mg Limit of quantification 0.01mg 0.02mg Regression equation (Y*) Y= x Y= x Slope (B) Intercept (A) Correlation coefficient (R 2 ) Y=A + Bx, where x is the concentration of analyte and y is the absorbance value 375

5 Similarly FT-IR spectra was recorded for synthetic mixture containing 1:15 ratio of DMP and RAN respectively (Figure 6). The spectra clearly shows the two peaks pertaining to RAN and DMP at the corresponding wave numbers (1620cm -1, 1717cm -1 ) without any interference. Quantification of both the drugs (RAN & DMP) in synthetic mixture was carried out using calibration method. To find out the unknown concentrations of the drug known weights of the sample (synthetic mixture) spectra were recorded in the region (2000cm -1 to 1500cm -1 ) of the corresponding wave numbers of the individual drug. Absorbance values were measured at the respective peak wave numbers 1620cm -1 (RAN) and 1717cm -1 (DMP). The concentration of the unknown drug was estimated from calibration plots of synthetic mixture using the absorbance values. The amount, standard deviation and % RSD were calculated and tabulated in Table 2. The results revealed that both the drugs followed Beer-Lamberts law in the concentration range studied. S. No. Table 2: Quantification of RAN and DMP in Synthetic mixture Compound Amount of drug Taken (mg) % Recovery Estimated* [Mean ± SD] %RSD Ranitidine ± ± ± ± Domperidone ± ± ± ± *Mean (η=5) Table 3: Recovery studies of commercial formulations Label claim Amount found Average of 5 % Tablet (mg/tablet) (mg/tablet) determinations Estimated RSD label claim (%) RANTAC D Ranitidine Domperidone The method was applied to combined dosage formulation and the spectrum was recorded for RANTAC D tablet (Figure 2). From the spectrum it was observed that the peaks (1620cm -1 and 1717cm -1 ) were free from interferences from other compound present in the tablet (excipients). Table 3 shows the recovery and % RSD ( =5) for commercial tablet RANTAC D. The % RSD 376

6 was found to be 2.17 and 1.54 for RAN and DMP respectively. The co-efficient of correlation (R 2 ) was calculated from the calibration and found it to be (RAN) and (DMP). The recovery was found to be >99%. The values of recovery, RSD and coefficient of correlation show high precision of the method. The estimation of both RAN and DMP in tablets by the proposed method yielded precise results indicating the reliability of the method. CONCLUSIONS In the present investigation we have studied the possibility of quantification of drug components in combined dosage formulations using FT-IR. From the data it is clear that FT-IR is capable of direct determination of RAN and DMP in the above formulations. The proposed FT-IR method was found to be simple, rapid and reproducible and less time consuming compared to UV- Spectrophotometric methods, which exists in literature. REFERENCES 1. Rajendra Prasad Y, Rajasekhar KK, Shankarananth V, Yaminikrishna HV, Saikumar S, Venkata raghav reddy P, Spectrophotometric Method for the Estimation of Domperidone inbulk and Pharmaceutical Formulations. J Pharm Res 2009; 2: Zarapkar SS, Salunke BB, Determination of Domperidone by High Performance Thin Layer Chromatography in Pharmaceutical Preparation (HPTLC), Indian Drugs, 1990; 27: Khalil I Al-Khamis, Hagga MEM, Hamad A Al-Khamees, Mahmoud Al-awadi, Spectrophotometric Determination of Domperidone using δa Method. Anal Lett 1990; 23: Pallavi Salve, Deepali Gharge, Rupali Kirtawade, Pandurang Dhabale, Kishore Burade. Simple Validated Spectroscopic Method for Estimation of Ranitidine from Tablet formulation. Int J Pharm Tech Res 2010; 2(3): Patil VS, Gaikwad PD, Bankar VH and Pawar SP. Formulation and Evaluation of floating Matrix tablet of locally acting H2-Antagonist, Int J Pharm Tech, 2010; 2(3): Punitha K, Khadhir S, Ravichandiran V, Umadevi SK, Vaijayanthi V, Padmapriya S, Suresh Kumar S. Intragastric floating Drug Delivery system of Ranitidine Hydrochloride: Formulation and Evaluation. Int J Pharm Sci 2010; 2 (4): Angus Forster, Keith Gordon, David Schmierer, Nathan Soper, Vivian Wu and Thomas Rades, The Internet Journal of Vibration Spectroscopy; Contributed Article, 1998; 2, Aneta Sokol, Joanna Karpinska, Renata Telecka and Barbara Starczewska. Quantification of Ranitidine Hydrochloride in the presence of its decomposition product by 377

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