A. Brief resume of the intended work:

A.1. Need for study

Parkinsonism is chronic progressive disorder of the central nervous system, which is the result of damage

to cells located in the basal ganglia of the brain. It leads to disturbances in gait impaired speech, muscle weakness and autonomic hyperactivity like salivation and seborrhea. There are many antiparkinsonian drug combinations available in market, Trifluoperazine hydrochloride and Trihexyphenidyl hydrochloride is a combination in market used for the treatment of Parkinsonism .1, 2

Trifluoperazine hydrochloride is a trifluoro-methyl phenothiazine derivative intended for the management of Schizophrenia and other psychotic disorders. Trifluoperazine hydrochloride blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain and depresses the release of hypothalamic and hypophyseal hormones and is believed to depress the reticular activating system thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and emesis.1,2,3

Trihexyphenidyl hydrochloride is an anticholinergic used in the symptomatic treatment of all etiologic groups of Parkinsonism and drug induced extrapyramidal reactions (except tardive dyskinesia). Trihexyphenidyl hydrochloride possesses both anticholinergic and antihistaminic effects, although only the former has been established as therapeutically significant in the management of Parkinsonism.1, 2, 4

Trihexyphenidyl hydrochloride is a selective M1 muscarinic acetylcholine receptor antagonist it is able to discriminate between the M1 (cortical or neuronal) and the peripheral muscarinic subtypes (cardiac and glandular). Trihexyphenidyl hydrochloride partially blocks cholinergic activity in the CNS, which is responsible for the symptoms of Parkinson's disease. It is also thought to increase the availability of dopamine, a brain chemical that is critical in the initiation and smooth control of voluntary muscle movement.

Hence, investigation of new analytical methods is in need for the quantitative estimation of Trifluoperazine hydrochloride and Trihexyphenidyl hydrochloride, individual as well as in combination in bulk drug and pharmaceutical dosage form.

A.2. Review of literature:

Chemically Trifluoperazine hydrochloride is 10-[3-(4-methylpiperazin-1-yl) propyl]-2-(trifluoromethyl) phenothiazine hydrochloride.5, 6 Molecular formula is C21H24F3N3S 5, 7 and molecular weight is 407.5.5 It is freely soluble in water, ethanol and methanol.5,8 Melting point is 242 to 115 0C.5

Chemically Trihexyphenidyl hydrochloride is 1-cyclohexyl-1-phenyl-3-piperidin-1-ylpropan-1-ol hydrochloride.7,9 Molecular formula is C20H31NO5 and molecular weight is 337.94.5 It is freely soluble in water, ethanol and methanol.5,8 Melting point is 114.3 to 1150C.3, 5

Literature survey reveals that no methods have been developed for the simultaneous estimation of Trifluoperazine hydrochloride and Trihexyphenidyl hydrochloride. But only two methods are developed for estimation of Trifluoperazine hydrochloride such as UV-visible spectroscopic method10 and HPLC11 method. Where as two HPLC12 methods have been developed for the estimation of Trihexyphenidyl in bulk drug and in pharmaceutical dosage form. One LC-ESI-MS 13 and one radioimmunoassay for Trihexyphenidyl.14

The chemical structure of Trihexyphenidyl (I) 7 and Trifluoperazine (II) 7 are;

(I)

B. Materials and Methods

B. 1. Objectives of the study:

No methods have been developed for the simultaneous estimation of Trifluoperazine hydrochloride and Trihexyphenidyl hydrochloride in bulk drug and in pharmaceutical dosage form.

In view of above fact various analytical methods are planned to develop with accuracy, precision, economy and sensitivity.

1. UV/Visible Spectrophotometric methods can be developed for the simultaneous estimation of Trifluoperazine hydrochloride and Trihexyphenidyl hydrochloride bulk drug and in pharmaceutical dosage form.

2. Reversed phase HPLC methods can also be done for simultaneous estimation of Trifluoperazine hydrochloride and Trihexyphenidyl hydrochloride.

3. HPLC methods can be developed for the estimation Trifluoperazine hydrochloride and Trihexyphenidyl hydrochloride individually and in pharmaceutical dosage form.

4. HPTLC methods can be developed for the estimation of Trifluoperazine hydrochloride and Trihexyphenidyl hydrochloride individually and in pharmaceutical dosage form.

In the present investigation of the new analytical methods for quantitative estimation of Trifluoperazine and Trihexyphenidyl hydrochloride, we are in need and using Double beam UV/Visible spectrophotometer (Shimadzu 1700), HPLC (Knauer pump K-501, U.V Detector K-2501), other chromatographic instruments and volumetric glass apparatus.

B.2. Source of data:

a.  Internet, National College of Pharmacy, Shimoga.

b.  Digital Library, RGUHS, Bangalore.

c.  Library, National College of Pharmacy, Shimoga.

d.  Central Library, Kuvempu University, Shimoga.

B.3. Method of Collection of data (Including sampling procedures, if any)

Data’s were collected from:

1)  Internet, National College of Pharmacy, Shimoga.

2)  Analytical and Chemical Abstracts – Digital Library, RGUHS, Bangalore; and Library, National College of Pharmacy, Shimoga

3)  Chinese Journal of Chromatography, Journal of Pharmaceutical and Biomedical Analysis, Indian Journal of Pharmaceutical Sciences, Indian Journal of Analytical Chemistry, Analyst, Indian Journal of Chemical Sciences, Indian Journal of Chemical Technology, Asian Journal of Chemistry etc.

B.4. – Not applicable -

B.5. – Not applicable -


C. References:

  1. Joel GH, Lee EL, Perry BM, Raymond WR, Alfred Cg, editor. Goodman Gilman’s the pharmacological basis of therapeutics. 9th ed. New Jersy: McGraw Hill Companies; 1996.
  2. Rang HP, Dale MM, More KP, Text book of pharmacology. 5 th ed
  3. http://en.wikipedia.org/wiki/trifluroperazine
  4. http://en.wikipedia.org/wiki/trihexyphenidyl
  5. Neil MJ, editor. The Merck Index- an Encyclopedia of Chemicals, Drugs and Biologicals. 13th ed. New Jersy: Merck and Co; 2001.
  6. http://www.drugbank.ca/drugs/DB00376
  7. Sweetmann SC, editor. Martindale-The Complete Drug Reference. 33rd ed. London: Pharmaceutical press; 2002.
  8. Indian Pharmacopoeia. 2007; Vol I: page no 162
  9. http://www.drugbank.ca/drugs/DB00831
  10. Kapka, Yan XU, Yong Hong Chen. Stereoselective determination of Trihexyphenidyl in human serum by LC-ESI-MS. J Pharma and Biomed Anal.1999; 21(3):507-17.
  11. Mahadik KR, AggrawalH, Maul N. Development and validation of HPLC method for simultaneous estimation of Trihexyphenidyl hydrochloride and Chlorpromazine hydrochloride from tablet dosage. J Pharma Sci.ISSN0019-462X CodenIndrba.
  12. Bhongade SL, Kasture AV. Spectrophotometric determinations of Phenothiazine derivatives. Ind J Pharma Sci 1996; 58: 258-261.
  13. Saudagar RB, Swarnlata S, Saraf S. Spectrophotometric determination of Chlordiazepoxide and Trifluoperazine hydrochloride from combined dosage. Ind J Pharma Sci. 2007; 69: 149-152.
  14. Handan H, McKay G, Wirshing B , Kamal K. Development and application of a specific and sensitive radioimmunoassay for Trihexyphenidyl to a pharmacokinetic study in humans. J Pharma Sci ISSN0022-3549CodenJpmsae
  15. Gennarora RA, Remington, The science and practice of pharmacy 20th ed .vol IV. Lippnocott, Williams and Wilkins. 2000

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