Absorption Ratio Method for Simultaneous Estimation of Haloperidol and Trihexyphenidyl in Tablet
Sharad Pawar College of Pharmacy, Wanadongri, Hingna Road, Nagpur – 441 110
*Corresponding Author E-mail: Indiaanshu@rediffmail.com
ABSTRACT
A simple, accurate, economical and reproducible procedure for simultaneous estimation of haloperidol (HP) and trihexyphenidyl (THP) in their tablet dosage form is described. The method involves absorbance measurement at 218.8 nm (isobestic point) and 245.0 nm (λmax of haloperidol), in methanol and 0.1N HCl (90:10). Both the drugs obey Beer Lambert’s law in the concentration range of 2.5-12.5 µg/ml (HP) and 1.0-5.0 µg/ml (THP). The results of analysis have been validated statistically and by recovery studies.
KEYWORDS: Haloperidol, Trihexyphenidyl, Validation
INTRODUCTION:
Haloperidol is 4-[4-(4-chlorophenyl)-4-hydroxy-1-piperidyl]-1-(4-fluorophenyl)-butan-1-one and is an anti-dyskinetic and anti-psychotic drug while trihexyphenidyl is 1-cyclohexyl-1-phenyl-3-(1-piperidyl)-1-propanol and is an anti-dyskinetic and anti-parkinson drug.1 Haloperidol is official in BP2 and trihexyphenidyl in IP3. BP suggests titrimetric assay method for haloperidol. IP suggests titrimetric assay method for trihexyphenidyl. Literature survey revealed that HPLC4, 5 methods have been reported for the estimation of haloperidol and trihexyphenidyl individually and with other drugs in pharmaceutical dosage forms. However, no method is reported for the simultaneous estimation of these drugs in combined dosage forms. This prompted us to develop simple, rapid, accurate, economical and sensitive spectrophotometric method for their combination.
MATERIAL AND METHODS:
Shimadzu 1700 UV/Vis spectrophotometer with matched cuvettes was used for the experimental work. The chemicals used were of analytical grade. Commercially available tablets of haloperidol and trihexyphenidyl in combination were procured from local market. Standard haloperidol and trihexyphenidyl were received as gift samples from Stadmed Pvt. Ltd., Kolkata.
Preparation of Standard Solution:
Standard stock solutions of haloperidol and trihexyphenidyl were prepared separately by dissolving 25 mg each of standard haloperidol and trihexyphenidyl in methanol and 0.1N HCl (90:10) and making up the volume to 50 ml with same solvent.
Standard solutions (25 µg/ml) HP and THP were further prepared by taking 2.5 ml of stock solution of each drug in two 50 ml volumetric flasks separately and making up the volume to the mark with same solvent.
Overlain spectra of standard solutions of haloperidol and trihexyphenidyl were obtained and scanned between 200 nm – 300 nm (Fig.1).
Haloperidol showed absorption maxima at 245.0 nm and trihexyphenidyl showed at 218.8 nm. Calibration curve for each drug was prepared in the concentration range of 2.5-12.5 µg/ml (HP) and 1.0-5.0 µg/ml (THP) at corresponding wavelengths i.e. 245.0 nm and 218.8 nm. Amount of each drug was determined using equation as follows-
Qm – Qy A Qm – Qx A
Cx = ------------- x ------ Cy = ------------- x ------
Qx – Qy Ax1 Qy – Qx Ay1
Where, Cx = Concentration of HP in g/100 ml. Cy = Concentration of THP in g/100 ml. Qm = Ratio of absorbance of laboratory mixture at 245.0 nm and 218.8 nm. Qx = Ratio of absorptivity of HP at 245.0 nm and 218.8 nm. Qy = Ratio of absorptivity of THP at 245.0 nm and 218.8 nm. Ax1 = Absorptivity of HP at 218.8 nm. Ay1 = Absorptivity of THP at 218.8 nm. A = Absorbance of laboratory mixture at isobestic point.
C x D
% Estimation = ---------- x 100
W
Where, C = Cx or Cy = Concentration of HP or THP in g/100 ml. D = Dilution factor. W = Weight of drug (either HP or THP) in laboratory mixture.
Table 1: Results of statistical data of marketed formulation
|
Tablet component |
Label claim (mg/tab) |
SD |
% RSD |
SE |
|
|
Halotex |
Haloperidol |
5 |
0.7829 |
0.7844 |
0.3501 |
|
Trihexyphenidyl |
2 |
0.2698 |
0.2690 |
0.1206 |
Table 2: Results of drug recovery study
|
Amount of pure drug added (µg/ml) |
% Recovery |
SD |
||||
|
HP |
THP |
HP |
THP |
HP |
THP |
|
|
|
2 |
2 |
99.43 |
99.50 |
|
|
|
4 |
4 |
99.33 |
99.83 |
|||
|
6 |
6 |
99.81 |
99.50 |
|||
Fig. 1: Overlain spectra of haloperidol and trihexyphenidyl in methanol and 0.1N HCL (90:10). 218.8 nm is the isobestic point.
Preparation of Sample Solution:
Marketed tablets ‘Halotex’ (Triton Health Care Pvt. Ltd., Chennai) were used for the simultaneous estimation of HP and THP. Twenty tablets were weighed and crushed to fine powder. Powder equivalent to 50 mg of haloperidol and 20 mg of trihexyphenidyl (tablet contains 5 mg haloperidol and 2 mg trihexyphenidyl) was dissolved in the solvent and volume was made up to 50 ml. Insoluble excipients were separated by filtration. The filtrate was further diluted to get final concentration of both the drugs in the linearity range. Absorbance was noted at the selected wavelengths and percent label claim was determined by using the equation.
Cx or Cy x D x W
% Label claim = ------------------------ x 100
Wm x L
Where, Cx or Cy = Concentration of HP or THP in g/100 ml. W = Average weight of tablet. Wm = Weight of sample taken. L = Label claim of sample taken.
Validation of Proposed Method:6
The reproducibility, repeatability and accuracy of the proposed method were found to be satisfactory which is evident from the low values of standard deviation (SD), percent relative standard deviation (RSD) and standard error (SE) (Table 1).
The accuracy and reproducibility of the proposed method was confirmed by recovery experiment, performed by adding known amount of the drugs to the preanalyzed formulations and reanalyzing the mixture by proposed method (Table 2).
The percent recovery obtained indicates non–interference from the excipients used in the formulation. Thus, the method developed in the present investigation is found to be simple, sensitive, accurate and precise and can be successfully applied for the simultaneous estimation of Haloperidol and Trihexyphenidyl in tablets.
ACKNOWLEDGEMENTS:
The authors wish to thank Principal Dr. K. P. Bhusari, Sharad Pawar College of Pharmacy, Rashtrasant Tukadoji Maharaj Nagpur University for providing necessary facilities. Also, thanks to Stadmed Pvt. Ltd., Kolkata for providing the authentic sample of drugs.
REFERENCES:
1. Maryadele, S., In; The Merck Index, 13th Edn, Merck and Co., Inc., Whitehouse Station, NJ, 2001, 4611, 9770.
2. British Pharmacopoeia, Vol. I, The British Pharmacopoeia Commission, London, 2008, 1047.
3. Indian Pharmacopoeia, Vol. I, New Delhi, the controller of publications, Govt of India, 1996, 91.
4. RP-HPLC Estimation of Haloperidol and Propantheline bromide in Tablets or Capsules. Sane R. T., Ghadge J. K., Jani A.B., Vaidya A. T. and Kotwal S. S., Indian Drugs, 29(5), 1992, 240-244.
5. RP-HPLC Estimation of Trihexyphenidyl HCl and Chlorpromazine HCl in Tablets. Mahadik K. R., Aggarwal H. and Kaul N., Indian Drugs, 39(8), 2002, 441-445.
6. International Conference on Harmonization (ICH), Draft guidelines on validation of analytical procedure- definition and terminology, Federal Register, 1995, 60, 11260-11262.
Received on 30.03.2009 Modified on 15.06.2009
Accepted on 21.08.2009 © RJPT All right reserved
Research J. Pharm. and Tech.2 (3): July-Sept. 2009,;Page 603-604