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RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
BANGALORE, KARNATAKA
ANNEXURE –ІІ
REGISTRATION OF SUBJECT FOR DISSERTATION
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NAME OF THE CANDIDATE
ADDRESS
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NAME OF THE INSTITUTION
NAGARJUNA
CHITTIBOMMA,
D-NO- 14, MARUTHI NILAY,
12TH CROSS, 4TH MAIN,
BEHIND SINDHE HOSPITAL,
SAMPAGIRAMNAGAR,
BANGALORE-27.
Al-Ameen College of Pharmacy,
Bangalore.
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COURSE OF STUDY &
M.Pharm.,Part-1
SUBJECT
Quality Assurance
DATE OF ADMISSION
9th June 2008
TITLE OF THE TOPIC
Simultaneous Estimation of Doxylamine succinate and Pyridoxine
hydrochloride in Marketed Formulations by Instrumental Methods.
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6.0
BRIEF RESUME OF THE INTENDED WORK:
6.1
Analytical chemistry :
The study of the chemical composition of natural and artificial materials. Unlike
other major sub disciplines of chemistry such as inorganic chemistry and organic
chemistry, analytical chemistry is not restricted to any particular type of
chemical compound or reaction. Properties studied in analytical chemistry
include geometric features such as molecular morphologies and distributions of
species, as well as features such as composition and species identity. The
contributions made by analytical chemists have played critical roles in the
sciences ranging from the development of concepts and theories (pure science)
to a variety of practical applications, such as biomedical applications,
environmental monitoring, quality control of industrial manufacturing and
forensic science (applied science).
6.2
Modern analytical chemistry:
Modern analytical chemistry is dominated by instrumental analysis. Many
analytical chemists focus on a single type of instrument. Academics tend to
either focus on new applications and discoveries or on new methods of analysis.
Types:
Qualitative:

Qualitative inorganic analysis seeks to establish the presence of a given
element or inorganic compound or functional group or organic compound
in a sample.
Quantitative:

Quantitative analysis seeks to establish the amount of a given element or
compound in a sample.
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6.3
Analytical Method Development:
Provides the support to track the quality of the product from batch to
batch. Typically analytical methods will need to be validated for the specific
product at or before phase III clinical trials. Capabilities includes:

.Method development , qualification and validation.

Drug substance quality determination and in process analysis.

Characterization of reference materials(chemical and physical properties)
Method development is done for the following type of the products:

New products.

Existing products.
Methods are developed for those products where no official methods
are available. Alternate methods for existing (non-pharmaceutical) products are
developed to reduce the cost and time for better precision and ruggedness. Trial
runs are conducted, method is optimized and validated. When alternate method
proposed is intended to replace the existing procedure comparative laboratory
data including merits/demerits are made available.
Simultaneous estimation is the determination of the individual component from
the formulation of two or more components, by separating them and assaying
individually.
Simultaneous estimation can be performed by the following two methods:

Titrimetric method

Instrumental method
Titrimetric methods are labour intensive, time consuming and hence
nowadays, generally instrumental methods are preferred. Instrumental methods
are most favorable for multicomponent dosage forms. One such combination
prescribed is Doxylamine succinate and Pyridoxine hydrochloride marketed
formulation. No method has been found in the literature for simultaneous
determination of this combination.
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A.Doxylamine succinate:
Doxylamine succinate is an antihistamine. Depending on product, it may
be used to fall asleep or used to relieve symptoms of allergy, hay fever, and the
common cold. This medication works by blocking certain natural substances
(histamine, acetylcholine).This effect causes drowsiness and also helps to relieve
allergy cold symptoms such as watery eyes, runny nose, and sneezing. It is one
of the many sedating antihistamines used by itself as a short-term sedative, in
combination with other drugs as a night-time cold and allergy relief drug, and a
preparation is prescribed in combination with vitamin B6 (pyridoxine) to prevent
morning sickness in pregnant women. It will be avilable in market in the form of
tablets having brand names like Restavit, Dozile & Nyquil.
Chemical Name: Pyridine, 2-(alpha-(2-(dimethylamino)ethoxy)-alpha-methylbenzyl)-,
succinate(1:1)
Chemical Formula: C17-H22-N2-O.C4-H6-O4
B.Pyridoxine Hydrochloride:
Pyridoxine hydrochloride, (5-hydroxy-6methylpyridine3,4dimethyl)
dimethanolhydrochloride is a white crystalline powder (structure 1), used in
treatment of sideroblastic anemia’s; it is readily absorbed from the
gastrointestinal tract on oral administration and is converted to the active forms,
pyridoxal phosphate and pyridoxamine phosphate, which are stored mainly in
the liver where there is oxidation to 4-pyridoxic acid and other metabolites that
are excreted in the urine. It is involved in amino acid as well as carbohydrate and
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fat metabolism. It is used in a variety of disorders, including the treatment of
depression and other symptoms
.Hcl
6.4
OBJECTIVE OF STUDY:
In the proposed work, attempt shall be made :

To develop and validate simple, precise and accurate stability indicating
HPLC method for simultaneous determination of Doxylamine succinate
and Pyridoxine hydrochloride.

The method shall be validated by using various analytical parameters
such as accuracy, precision, specificity, robustness, ruggedness, linearity
and range.
6.5
Method and Instrumentation:
HPLC Method:
High Performance Liquid Chromatography is one of the most
powerful tools on analytical chemistry, with the ability to separate, identify and
quantitative the compounds that are present in any sample that can be recorded
in a liquid, even trace concentration of compounds as low as “parts per trillion”
are easily obtained. This technique could be employed for simultaneous
determination of the combination product. The principle involved in this method
is differential partition and differential adsorption depending upon column used.
The HPLC instrument for separation, isolation and detection
of the drug combination. Mobile phase and solvent system will be selected as per
the results obtained from the basis of pKa studies and also trial and error method.
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7.0
REVIEW OF LITERATURE:
Literature was referred for estimation of Doxylamine succinate and
Pyridoxine hydrochloride in marketed dosage form. It was found that a few
methods have been reported for these drugs individually or in combination with
other drugs. The collection of references are reproduced below:

Argekar AP., Sawant J.G.,4 performed Simultaneous determination of
pyridoxine hcl & doxylamine succinate from tablets by ion pair reversed
phase HPLC using C18 column & mobile phase water:methanol with UV
detector.

Pathak A., Rajput S.J.5, performed Simultaneous determination of a
tertiary mixture of doxylamine succinate, pyridoxine hcl & folic acid by
the ratio spectra-zero-crossing, double divisor-ratio spectra derivative &
HPLC
by using UV detection at 263 nm at different concentration
ranges.

Pons M.L., Romero J.S., et al,6 performed Spectrophotometric
determination of
the antihistamines, carbinoxamine maleate &
doxylamine succinate, in an N-cetylpyridinium chloride micellar
medium..

Aslam J., Mahajir M.J., et al7, performed
HPLC analysis of water
soluble vitamins in in vitro & ex vitro grminated chickpea Using C18
column at a flow rate of 1.0ml/min with the use of UV detector at a wave
length of 283 nm.

Mai K., Zhu W., Getian WU.8, performed Pyridoxine requirement of
juvenile ablone, haliotis discus hannai ino. By using HPLC with ODS
hypersil column at a flow rate of 1.0ml/min. ditection done by using
diode array detector.

Arayne MS., Sultana N.9, performed Spectrophotometric methods for the
simultaneous analysis of meclezine hcl & pyridoxine hcl in bulk drug &
pharmaceutical formulations. By using UV-vissible double beam
spectrophotometer mfg by shimadzu, 1601 version.
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
Sethi P.D., Chatterjee P.K., Kumar Y.10, performed Simultaneous
Spectrophotometric determination of vitamin B1, B6, & B12
in
formulations.

Zarapkar S.S., Halkar U.P; Rane S.H.11 performed Reverse phase HPLC
determination of doxylamine succinate & pyridoxine hcl in tablets.

Kohlhof
K.J; Stump D., Zizzamia J.A.12 performed Analysis of
doxylamine in plasma by HPLC.

Kall M.A13., performed Determination of total vitamin B6 in foods by
isocratic HPLC: a comparison with microbiological analysis.

Consigliere V.O., Vals NRM., Magalh J.M.14 performed First-derivative
spectrophotometric determination of pyridoxine hcl in pharmaceutial
preparations.
MATERIALS AND METHODS:
Source of data:
 References from library - Al-Ameen College of Pharmacy, Bangalore.
 References from Internet Browsing.
 www.sciencedirect.com
 www.google.com
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METHOD OF COLLECTION OF DATA:

All experiments shall be carried out in the Department of Quality
Assurance., Al-Ameen college of Pharmacy, Bangalore.

Pure samples of Doxylamine succinate & Pyridoxine Hcl shall be
procured from Industries involved in manufacture of these drugs.

The HPLC method shall be developed and validated in Q.A. lab of
AACP.
Does the study require any investigation to be conducted on patients or
animals?
No
Has the ethical clearance been obtained from your institution in case of
7.3?
Not applicable
8.0
References:
1. Sharma B.K, Instrumental methods of chemical analysis, An introduction
to Analytical Chemistry Goel Publication house, Meerut 2002;3:74.
2. Brirish Pharmacopoeia; British Pharmacopoeia commission. 2008; 76970.
3. Indian
Pharmacopoeia,
The
Indian
pharmacopoeia
commission,
Ghaziabad 2007; 1623-4.
4. Argekar AP., Sawant J.G., Simultaneous determination of pyridoxine hcl
& doxylamine succinate from tablets by ion pair reversed phase HPLC.
Drug development & industrial pharm j 1999;25:8, 945-50.
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5. Pathak A., Rajput S.J., Simultaneous determination of a tertiary mixture
of
doxylamine succinate, pyridoxine hcl & folic acid by the ratio
spectra-zero-crossing, double divisor-ratio spectra derivative & HPLC
methods. J aoac int 2008; 1059-69.
6. Pons M.L., Romero J.S., et al , Spectrophotometric determination of the
antihistamines, carbinoxamine maleate & doxylamine succinate, in an Ncetylpyridinium chloride micellar medium. Ana letters,1996;29:13991414.
7. Aslam J., Mahajir M.J., et al, HPLC analysis of water soluble vitamins in
in vitro & ex vitro grminated chickpea. African j of Biotech, 2008; 7(14)
2310-14.
8. Mai K., Zhu W., Getian WU., Pyridoxine requirement of juvenile ablone,
haliotis discus hannai ino. J of Shellfish research,2007;26:3, 815-20.
9. Arayne MS., Sultana N., Spectrophotometric methods for the
simultaneous analysis of meclezine hcl & pyridoxine hcl in bulk drug &
pharmaceutical formulations. Pak. J. Pharm. Sci.,2007;20.,149-56.
10. Sethi P.D., Chatterjee P.K., Kumar Y., Simultaneous Spectrophotometric
determination of vitamin B1, B6, & B12 in formulations. Ind J of Pharm
Sci., 1985; 118-9.
11. Zarapkar S.S., Halkar U.P; Rane S.H. Reverse phase HPLC
determination of doxylamine succinate & pyridoxine hcl in ntablets. Ind.
Drugs 1999; 36: 449-52.
12. Kohlhof
K.J; Stump D., Zizzamia J.A. Analysis of doxylamine in
plasma by HPLC. J of Phrm Sci 2006; 72:8; 961-2.
13. Kall M.A., Determination of total vitamin B6 in foods by isocratic HPLC:
a comparison with microbiological analysis. J of food Chem. 2003; 82:2;
315-27.
14. Consigliere
V.O.,
Vals
NRM.,
Magalh
J.M.
First-derivative
spectrophotometric determination of pyridoxine hcl in pharmaceutial
preparations. Ana letters 2001; 34:11; 1875-88.
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9.0
SIGNATURE OF THE CANDIDATE
10.0
REMARKS OF THE GUIDE
11.0
NAME AND DESIGNATION OF
11.1
GUIDE
11.2
SIGNATURE
11.3
CO-GUIDE
11.4
SIGNATURE
11.5
HEAD OF THE DEPT.
Forwarded for approval
Dr. Sanjay Pai P N
Professor and Head,
Dept of Quality Assurance
Dr. Sanjay Pai P N
Professor and Head,
Dept of Quality Assurance
11.6
SIGNATURE
12.0
REMARKS OF THE PRINCIPAL
SIGNATURE
Forwarded for approval
Prof. B.G. Shivananda
Principal,
Al-Ameen College of Pharmacy,
Hosur Road, Bangalore -27.
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