Download 6.4 a brief introduction about loratadine [10][11]

“DEVELOPMENT OF NEW ANALYTICAL METHODS AND THEIR VALIDATION
FOR THE DETERMINATION OF METOCLOPRAMIDE HYDROCHLORIDE AND
LORATADINE IN BULK AND MARKETED FORMULATIONS”
MASTER OF PHARMACY DISSERTATION PROTOCOL
SUBMITTED TO THE
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES KARNATAKA,
BANGALORE
BY
SOLANKI MEGHABEN JAGDISHBHAI
Under The Guidance of
DR. E.V.S. SUBRAHMANYAM. M.PHARM. Ph.D
P.G. DEPARTMENT OF QUALITY ASSURANCE,
SRINIVAS COLLEGE OF PHARMACY, MANGALORE – 574143
2011 – 2013
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
BANGALORE, KARNATAKA
ANNEXURE – II
REGISTRATION OF SUBJECT FOR DISSERTATION
1.0
NAME OF THE CANDIDATE
SOLANKI MEGHABEN JAGDISHBHAI
ADDRESS
DEPARTMENT OF Q.A.,
SRINIVAS COLLEGE OF PHARMACY,
VALACHIL,POST PARENGIPETE,
MANGALORE TQ-574143
2.0
NAME OF THE INSTITUTION SRINIVAS COLLEGE OF PHARMACY,
VALACHIL, MANGALORE.
COURSE OF STUDY &
MASTER OF PHARMACY
SUBJECT
(QUALITY ASSURANCE)
4.0
DATE OF ADMISSION
31st OCTOBER,2011
5.0
TITLE OF THE TOPIC:
3.0
“DEVELOPMENT OF NEW ANALYTICAL METHODS AND THEIR
VALIDATION FOR THE DETERMINATION OF METOCLOPRAMIDE
HYDROCHLORIDE AND LORATADINE
FORMULATIONS”
IN BULK AND MARKETED
6.0 BRIEF RESUME OF THE INTENDED WORK:
6.1 NEED FOR STUDY:
Analytical Method Development for Pharmaceutical Formulations:
Analytical methods are essential to characterize drug substances and drug products
composition during all stages of pharmaceutical development. For routine analytical
purpose it is always necessary to establish methods capable of analyzing large number of
samples in a short time period with high accuracy and precision
The number of drugs, which may be either new entities or partial structural
modification of the existing ones, introduced into the market is increasing every year. Very
often there is a time lag from the date of introduction of a drug into the market to the date
of its inclusion in pharmacopoeias. Hence, standards and analytical procedures for these
drugs may not be available in the pharmacopoeias. It becomes necessary, therefore to
develop new analytical methods for such drugs. These products can present challenges to
the analytical chemist responsible for the development and validation of analytical
methods.
Basic criteria for new method development of drug analysis:

The drug or drug combination may not be official in any pharmacopoeias.

A proper analytical procedure for the drug may not be available in the literature due
to patent regulations.

Analytical methods may not be available for the drug in the form of a formulation
due to the interference caused by the formulation excipients.

Analytical methods for a drug in combination with other drugs may not be
available.

The existing analytical procedures may require expensive reagents and solvents. It
may also involve cumbersome extraction and separation procedures and these may
not be reliable.
Analytical method development provides the support to track the quality of the product
from batch to batch. Estimation can be performed by the following two methods:

Titrimetric methods and

Instrumental methods.

Spectrophotometric Methods

Chromatographic Methods
Methods for analyzing drugs in dosage forms can be developed, provided one
has knowledge about the nature of the sample, its molecular weight, polarity, ionic
character and the solubility parameter. Method development involves considerable trial and
error procedures. The most difficult problem usually is where to start, what type of column
is worth trying with what kind of mobile phase.
Method development scheme for a typical HPLC-UV related substance describe below.
1. To define the goals for method development (e.g., what is the intended use of the
method?), and to understand the chemistry of the analytes and the drug product.
2. To develop preliminary HPLC conditions to achieve minimally acceptable
separations. These HPLC conditions will be used for all subsequent method
development experiments.
3. To develop a suitable sample preparation scheme for the drug product
4. To determine an appropriate standardization method and the use of relative
response factors in calculations.
5. To identify the “weaknesses” of the method and optimize the method through
experimental design. Understand the method performance with different conditions,
different instrument set ups and different samples.
6. To complete method validation according to ICH guidelines as mentioned in
Q2 (R1).
6.2 A BRIEF INTRODUCTION ABOUT METOCLOPRAMIDE
HYDROCHLORIDE[1]
MOLECULAR STRUCTURE:
IUPAC NAME: 4-amino- 5-chloro-N-(2-(diethylamino)ethyl)-2- methoxybenzamide
Hydrochloride
MOLECULAR FORMULA: C14H22ClN3O2·HCl
MOLECULAR WEIGHT: 336.26 g/mol
CATEGORY: Antiemetic and gastroprokinetic agent
PHYSICAL APPEARANCE: white, crystalline, odourless powder
SOLUBILITY: very soluble in water, freely soluble in alcohol, sparingly soluble in
methylene chloride
MELTING POINT: 147˚C (297˚F)
BIOAVAILABILITY: 80±15%(oral)
PROTEIN BINDING : 30%
METABOLISM: Hepatic
HALF-LIFE: 5 to 6 Hours
EXCRETION: 70-85% renal, 2% faecal
ROUTE: Oral, Intravenous, Intramuscular
PHARMACOLOGY:[1]
MEDICAL USES:
Metoclopramide hydrochloride is commonly used to treat nausea including that which is
due to chemotherapy and that occurring post operatively. Evidence also supports its use for
gastroparesis (poor stomach emptying) and gastroesophageal reflux disease.
Antiemetic: Metoclopramide hydrochloride commonly treats nausea and vomiting
associated with conditions such as uremia, radiation sickness, malignancy, labor, infection,
migraine headaches, and emetogenic drugs. In the setting of painful conditions such as
migraine headaches, Metoclopramide hydrochloride may be used in combination with
paracetamol (acetaminophen) (available in the UK as Paramax, and in Australia as
(Metomax) or in combination with aspirin (Migramax).
Gastroprokinetic: Metoclopramide hydrochloride increases peristalsis of the jejunum and
duodenum, increases tone and amplitude of gastric contractions, and relaxes the pyloric
sphincter and duodenal bulb. These gastroprokinetic effects make Metoclopramide useful
in the treatment of gastric stasis (e.g. after gastric surgery or diabetic gastroparesis ), as an
aid in gastrointestinal radiographic studies by accelerating transit through the
gastrointestinal system in barium studies, and as an aid in difficult intubation of the small
intestine. It is also used in gastroesophageal reflux disease (GERD).
Other Indications: By inhibiting the action of dopamine, Metoclopramide hydrochloride
has sometimes been used to stimulate lactation. It can also be used in the treatment of
migraines in the setting of allodynia, where it is more effective than triptans.
Veternary Use: Metoclopramide hydrochloride is also use in animals. It is commonly used
to prevent vomiting in cats and dogs. It is also used as a gut stimulant in rabbits.
MECHANISM OF ACTION:
Metoclopramide hydrochloride appears to bind to dopamine D2 receptors where it is a
receptor antagonist, and is also a mixed 5-HT3 receptor antagonist / 5HT4 receptor agonist.
The antiemetic action of Metoclopramide hydrochloride is due to its antagonist activity at
D2 receptors in the chemoreceptor trigger zone (CTZ) in the central nervous system (CNS)this action prevents nausea and vomiting triggered by most stimuli. At higher doses, 5-HT3
antagonist activity may also contribute to the antiemetic effect. The gastroprokinetic
activity of Metoclopramide hydrochloride is mediated by muscarinic activity, D2 receptor
antagonist activity and 5-HT4 receptor agonist activity. The gastroprokinetic effect itself
may also contribute to the antiemetic effect. Metoclopramide hydrochloride also increases
the tone of the lower esophageal sphincter.
ADVERSE EFFECTS:
Common adverse drug reaction (ADRs) associated with Metoclopramide hydrochloride
therapy include restlessness, drowsiness, dizziness, fatigue, and focal dystonia. Infrequent
ADRs include hypertension, hypotension, hyperprolactinaemia, leading to galactorrhea,
constipation, depression, headache, and extrapyramidal effects such as oculogyric crisis.
Rare but serious ADRs associated with therapy include agranulocytosis, supraventricular
tachycardia, hyperaldosteronism, neuroleptic malignant syndrome, akathisia and tardive
dyskinesia. Recent research suggests that Metoclopramide hydrochloride may be the most
common cause of drug-induced movement disorders. The risk of extrapyramidal effects is
increased in people under 20 year of age and with high dose of prolonged therapy. Tardive
dyskinesia may be persistent and irreversible in some patients. The majority of reports of
tardive dyskinesia occur in people who have used Metoclopramide hydrochloride for more
than three months. Consequently, the USFDA recommends that Metoclopramide
hydrochloride be used for short term treatment, preferably less than 12 weeks. In 2009, the
USFDA required all manufacturers of Metoclopramide hydrochloride to issue a black box
warning regarding the risk of tardive dyskinesia with chronic or high-dose use of the drug.
Dystonic reactions may be treated with benztropine, diphenhydramine, trihexyphenidyl or
procyclidine.
CONTRAINDICATIONS AND PRECAUTION:
Metoclopramide hydrochloride is contraindicated in phaeochromocytoma. It should be
used with caution in Parkinson’s disease since, as a dopamine antagonist, it may worsen
symptoms. Long-term use should be avoided in patients with clinical depression as it may
worsen mental state. Also contraindicated with a suspected bowel obstruction.
Use in pregnancy: Metoclopramide hydrochloride has long been used in all stages of
pregnancy with no evidence of harm to the mother or unborn baby. A large cohort study of
babies born to Israeli women exposed to Metoclorpamide hydrochloride during pregnancy
found no evidence that the drug increases the risk of congenital malformations, low birth
weight, preterm birth, or perinatal mortality. Metoclopramide hydrochloride is excrete into
milk.
6.3 REVIEW OF LITERATURE:
A literature survey was carried out for the estimation of Metoclopramide
hydrocloride in bulk and marketed dosage forms. It was found that a very few methods
have been reported for this drug. The collection of references are reproduced below:
1. Hosakere D. Revanasiddappa and Malligere A. Veena[2] have developed
sensitive spectrophotometric determination of Metoclopramide hydrochloride and
Dapsone in bulk sample and dosage forms. The method is based on the diazo –
coupling reaction of the studied drugs with a new coupling agent, imipramine
hydrochloride, in an acid medium. The resulting violet – colored azo dyes exhibit
maximum absorption at 570 nm for both Metoclopramide hydrochloride and
Dapson.
2. N. P. Dudhane, M. J. Umekar, R. T. Lohiya,[3] have developed a validated RPHPLC method for estimation of Metoclopramide hydrochloride and Paracetamol in
solid dosage form. RP-HPLC estimation of drugs in selected combination was done
using Phenomenex ODS 5μ, C18 column (250×4.6mm) and Acetonitrile:
Methanol: (0.5%) TEA Buffer (18.5:6.5:75) as mobile phase which shows sharp
and resolved peak when detected at 273nm.
3. Dudhane N.P., Vidhate S.S., Borkar B.H., Lohiya R.T., Umekar M.J[4]. have
developed
simultaneous UV spectrophotometric estimtion of Metoclopramide
hydrochloride and Paracetamol in solid dosage form.
Method I: Simultaneous Equation method, wavelengths selected were
243.0 nm and 273.5 nm for estimation of Metoclopramide
hydrochloride (MET) and Paracetamol (PAR) respectively.
Method II: Absorbance Ratio method, wavelengths selected were 243.0
nm, 262.0nm Isoabsorptive point of Paracetamol and
Metoclopramid hydrochloride.
Method III: Correction method,309.0 nm
4. Vinay
Wamorkar,
Manjunath
S.Y.,
M.Mohan
Varma[5],
have
done
development and validation of UV spectroscopic method for determination of
Metoclopramide hydrochloride in bulk and tablet formulation. Drug concentrations
in various tests were determined spectrophotometrically (SL‐164 Double beam UV
spectrophotometer, Elico, India.) at 272 nm using 1 cm quartz match cells.
5. Nawal. A. Al-Arfaj[6]
determination
of
has developed flow-injection chemiluminescent
Metoclopramide
hydrochloride
in
pharmaceutical
formulations and biological fluids using the [ru(dipy)32+]–permanganate system.
The method is based on the CL reaction of Metoclopramide with Ru(dipy)32+ and
KMnO4 in a sulfuric acid medium. Under the optimum conditions, a calibration
graph was obtained over the concentration range
0.005–3.5 _gml−1 with a limit
of detection (S/N = 2) of 1 ngml−1. The correlation coefficient was 0.99993 (n =
8) with a relative standard deviation of 0.48% for 10 determinations of 1 _gml−1 of
drug. The method was successfully applied to the determination of Metoclopramide
in pharmaceutical preparations and biological fluids after IP administration of 25
mg kg−1 dose to rats. The elimination half-life was 2.5 ± 0.4 h.
6. Ahmad Khan, Syed Baqir Shyum Naqvi, Muhammad Harris Shoaib, Rabia
Ismail Yousaf, Jallat Khan, Muhammad Hanif and Asadullah Madni [7] have
done validation and application of RP-HPLC method for the quantification of
Metoclopramide hydrochloride in oral formulations prepared for IVIVC studies. A
reverse chromatographic method was used with the mobile phase of Acetonitrile,
20m M.Potassium dihydrogen phosphate buffer solution (pH 3 adjusted with
orthophosphoric acid) in the ratio of 40:60.The column used was Waters C18
3.9×300mm μBondapak (RP). The flow rate of the mobile phase was 2ml/minute.
The detector was set at the wavelength of 275nm.
7. S R Patel, Dr. L J Patel[8] have done development and validation of first derivative
spectroscopy method for simultaneous determination of Ondansetron and
Metoclopramide in combined dosage form. The first derivative spectroscopy was
performed on a double beam UV Visible spectrophotometer using methanol as a
solvent. Absorbances were recorded at 266 nm (ZCP of ONDA) and 253 nm (ZCP
of METO) for Metoclopramide hydrochloride and Ondancetron, respectively.
8. Gaikwad Shubhangee, Kondawar Manish, Nazarkar Swapnil, Phase Sheetal
and Narkhede Harshal[9] have developed RPHPLC method for
the simultaneous determination of Metoclopramide hydrochloride and
Paracetamol in tablet dosage form. The method was carried out on a HiQsil
C8,
(4.6×250mm)
column
with
a
mobile
phase
consisting
of
acetonitrile:acetate buffer (pH 6.78) (50:50v/v) at a flow rate of 1ml/min.
Detection was carried out at 308 nm. The retention time of Paracetamol and
Metoclopramide hydrochloride was 3.2 and 5.5 min respectively.
6.4 A BRIEF INTRODUCTION ABOUT LORATADINE[10][11]
MOLECULAR STRUCTURE:
IUPAC NAME: ethyl 4-(8-chloro-5,6-dihydro-11 H-benzo[5,6]cyclohepta[1,2-b]pyridin11-ylidene)-1-piperidinecarboxylate
MOLECULAR FORMULA: C22H23ClN2O2
MOLECULAR WEIGHT: 382.88 g/mol
CATEGORY: H1 histamine antagonist ,drug used to treat allergies
PHYSICAL APPEARANCE: white to off white powder
SOLUBILITY: insoluble in water, soluble in acetone, alcohol and chloroform
BIOAVAILABILITY: Almost 100%
PROTEIN BINDING: 97-99%
METABOLISM: Hepatic(CYP2D6 and 3A4 mediated)
HALF LIFE: 8 Hours
EXCRETION: 40% as conjugated metabolites into urine, similar amount into the feces
ROUTES: ORAL
PHARMACOLOGY:[11][12]
MECHANISM OF ACTION:
Loratadine competes with free histamine and exhibits specific, selective peripheral H1
antagonistic activity. This blocks the action of endogenous histamine, which subsequently
leads to temporary relief of the negative symptoms (eg. nasal congestion, watery eyes)
brought on by histamine. Loratadine has low affinity for chlolinergic receptors and does
not exhibit any appreciable alpha-adrenergic blocking activity in-vitro. Loratadine also
appears to suppress the release of histamine and leukotrienes from animal mast cell, and
the release of leukotrienes from human lung fragments, although the clinical importance of
this is unknown.
ADVERSE EFFECTS:
As a“non sedative” antihistamine, Loratadine causes less (but still significant, in some
cases) sedation and psychomotor retardation than the older antihistamines because it
penetrates the blood brain barrier to smaller extent. Although drowsiness is rare at the
common 10 mg dose, patients should, nevertheless, be advised that it can occur and may
affect performance of skilled task (eg. driving). Patients should also avoid the use of
alcohol as it can increase the central nervous system depressing effects of Loratadine.
Other possible side effects include headache and antimuscarinic effects such as urinary
retention, dry mouth, blurred vision, and gastrointestinal disturbances.
DRUG INTERACTIONS:
Substances that act as inhibitors of the CYP3A4 enzyme such as ketoconazole,
erythromycin, cimetidine and furanocoumarin derivates (found in grapefruit) lead to
increased plasma levels of Loratadine. This had clinically significant effects in controlled
trials of higher than usual doses of Loratadine (20 mg). Antihistamines should be
discontinued approximately 48 hours prior to skin allergy tests since these drugs may
prevent to diminish otherwise positive reactions to dermal activity indicators.
CAUTION AND CONTRAINDICATIONS:
Patients with severe hepatic (liver) disorders may need to start with a lower dose. No dose
adaptation is necessary for elderly or renally impaired patients. Loratadine is usually
compatible with breast feeding (classified category L-2 by the American Academy of
Pediatrics). In the U.S., it is classified as category B in pregnancy, meaning that animal
reproduction studies have failed to demonstrate a risk to the fetus, and there are no
adequate and well controlled studies in pregnant women.
6.5 REVIEW OF LITERATURE:
A literature survey was carried out for the estimation of Loratadine in bulk and
marketed dosage forms. It was found that a very few methods have been reported for this
drug. The collection of references are reproduced below:
1. Krishna Veni Nagappan, Meyyanathan SN, Rajinikanth B Raja, Suresh Reddy,
Jeyaprakash MR, Arunadevi S Birajdar and Suresh Bhojraj[13] have developed
RP-HPLC method for simultaneous estimation of Ambroxol Hydrochloride and
Loratidine in pharmaceutical formulation. The method was carried out on a
Phenomenex Gemini C18 (25 cm x 4.6 mm i.d., 5 μ) column with a mobile phase
consisting of acetonitrile: 50mM ammonium acetate (50:50v/v) at a flow rate of 1.0
mL/min. Detection was carried out at 255 nm. Hydrochlorthiazide was used as an
internal standard.
2. K Basavaiah and V S Charan[14]
have developed spectrophotometric
determination of Astemizole and Loratadine based on charge-transfer complex
formation with chloranilic acid. The determination was based on the formation of
charge transfer complexes between chloranilic acid as a p - acceptor and the studied
drugs as n-donors in acetonitrile solvent. The spectra, various experimental
parameters, composition and formation constant of the complexes were studied. The
formation constant (K) values of CT complex with Astemizole were 0.9x103 and
1.06x103 calculated from Benesi-Hildebrand plot and from Turner and Anderson
plot, respectively, whereas the corresponding values for Loratadine were 4.50x103
and 4.19x103, respectively. The charge-transfer complexes formed were found to
absorb at 520 nm.
3. Georgeta Pavalache, Vasile Dorneanu And Antoanela Popescu[15]
have
developed validation of UV molecular absorption spectrophotomertric method for
Loratadine determination. Loratadine and potassium tetraiodomercuriate form a
macromolecule which can be detected by molecular absorption spectrometry in well
determined working conditions: reaction environment, the optimal amount of
reagent, time reaction. Detection wavelength was established at λ = 380 nm (at this
wavelength the compound shows maximum absorption in methanol in comparison
with maximum absorption Loratadine, which is at 288 nm).
4. Ilangovan Ponnilavarasan, Chebrolu.Sunil Narendra Kumar, And P.Asha [16]
have developed simultaneous estimation of Ambroxol hydrochloride and Loratadine
in tablet dosage form by using UV Spectrophotometric method. The method
employs measurement of absorbance at two wavelengths, 308nm and 245nm, of
Ambroxol and Loratadine respectively. Beer´s law obeyed in the concentration
range of 10-50&g/ml and 10-50&g/ml for Ambroxol and Loratadine respectively.
5. F.J. Rupe´rez, H. Ferna´ndez, C. Barbas[17] have developed LC determination of
Loratadine and related impurities. A HPLC method employing a Symmetry Shield
RP8 column has been developed and validated for Loratadine and related
compounds measurement, the last ones under the 0.1% level. The mobile phase
consisted of methanol-buffer A (65:35, v/v), being buffer A: H3PO4 10 mM (H2O)
brought up to pH 7.00 with triethylamine. UV detection was performed at 244 nm..
6. Radhakrishna T., Narasaraju A.,Ramakrishna M.,Satyanarayana[18] studied
high performance liquid chromatography (HPLC) and second derivative
spectrophotometry for the simultaneous determination of Montelukast and
Loratadine in pharmaceutical formulations, HPLC separation was achieved with a
Symmetry C18 column and sodium phosphate buffer (pH adjusted to
3.7):acetonitrile (20:80, v/v) as eluent, at a flow rate of 1.0 ml/min. UV detection
was performed at 225 nm. In the second-order derivative spectrophotometry, for the
determination of Loratadine the zero-crossing technique was applied at 276.1 nm,
but for Montelukast peak amplitude at 359.7 nm (tangent method) was used. Both
methods were fully validated and a comparison was made for assay determination of
selected drugs in formulations.
6.6 OBJECTIVES OF THE STUDY:
In the proposed work, attempt shall be made :
 To develop a new instrumental method for estimation of Metoclopramide
hydrochloride and Loratadine
To develop a validated method according to ICH guidelines.
 To apply validated method for the estimation of Metoclopramide hydrochloride and
Loratadine in pharmaceutical formulation.
7.0 7.1 Materials And Methods:
 All experiments will be carried out in the Department of Quality Assurance.
Srinivas college of Pharmacy, Valachil, Mangalore.
 Pure sample of Metoclopramide hydrochloride and Loratadine will be procured
from Industries involved in bulk manufacture of this drug.
 Dosage formulation will be procured from local market.
 The methods will be developed and validated in Q.A. lab of Srinivas college of
Pharmacy.
 The methods will be first developed, then Validated as per ICH guidelines, then
the method will be applied to the formulations.
 UV spectrophotometer Shimadzu-UV1700 with spectral band width of 2nm and
10nm and matched quartz shall be used for measuring absorbance for
Metoclopramide hydrochloride and Loratadine solutions.
 Reagents supposed to use for the estimation.

3-methyl,2-benzothiazolinehydrazone,(MBTH)

1,10-phenanthroline,

4-amino phenazene,

Para dimethyl amino benzaldehyde (PDAB)

Folin Ciocaltaeau reagent
In combinations

3-methyl 2-benzothiazoline hydrazine and cerric ammonium
sulphate

3-methyl 2-benzothiazoline hydrazineand and ferric ammonium
sulphate etc. can be used as reagents for Spectrophotometric method
development.
7.2 Sources of data:
 References from library – Srinivas College of Pharmacy, Valachil, Mangalore.
 www.pharmainfo.net.
 www.google.com
 www.sciencedirect.com
 www.rxlist.com
 www.pubmed.com
 www.medline.com
 www.wikipedia.com
7.3 Does the study require any investigation to be conducted on patients or animals?
No
7.4 Has the ethical clearance been obtained from your institution in case of 7.3 ?
Not applicable
8.0 REFERENCES:
1. en.wikipedia.org/wiki/metoclopramide hydrochloride
2. Hosakere D. Revanasiddappa and Malligere A. Veena, sensitive spectrophotometric
determination of Metoclopramide hydrochloride And Dapsone in Bulk Sample And
Dosage Forms. ScienceAsia;2006;32:319-321
3.
N. P. Dudhane, M. J. Umekar, R. T. Lohiya, a validated RP-HPLC method for
estimation of Metoclopramide hydrochloride and Paracetamol in solid dosage form.
JPR 2010, 3(12):3064-3066
4. Dudhane N.P., Vidhate S.S,. Borkar B.H., Lohiya R.T., Umekar M.J., simultaneous
UV
spectrophotometric
estimtion
of
Metoclopramide
hydrochloride
and
Paracetamol in solid dosage form.J. Pharm. Sci. & Res.2010;.2(1): 48-52
5. Vinay Wamorkar,Manjunath S.Y., M. Mohan Varma, development and validation
of UV spectroscopic method for determination of Metoclopramide hydrochloride in
bulk and tablet formulation. IJPRS, 2011; 3(3);171-174
6. Nawal.
A.
Al-Arfaj,
flow-injection
chemiluminescent
determination
of
Metoclopramide hydrochloride in pharmaceutical formulations and biological fluids
using the [ru(dipy)32+]–permanganate system, Talanta 2004;62: 255–263
7. Ahmad Khan, Syed Baqir Shyum Naqvi, Muhammad Harris Shoaib, validation and
application of RP-HPLC method for the quantification of Metoclopramide
hydrochloride in oral formulations prepared for IVIVC studies. Pak. J. Pharm.
Sci.,2012January;25(1):135-140
8. S R Patel, Dr. L J Patel, development and validation of first derivative spectroscopy
method for simultaneous determination of Ondansetron and Metoclopramide in
combined dosage form. International Journal of Pharmacy and Pharmaceutical
SciencesIJPRS 2011;3(4):85-88
9. Gaikwad Shubhangee, Kondawar Manish, Nazarkar Swapnil, Phase Sheetal and
Narkhede Harshal, developed RPHPLC method for the simultaneous determination
of Metoclopramide hydrochloride and Paracetamol in tablet dosage form. IJPLS
2010July;1(3):127-132
10. www.chemicalland21.com/lifescience/phar/LORATADINE.htm
11. en.wikipedia.org/wiki/loratadine
12. www.drugbank.ca/drugs/loratadine/DB00455
13. Krishna Veni Nagappan, Meyyanathan SN, Rajinikanth B Raja, Suresh Reddy,
Jeyaprakash MR,Arunadevi S Birajdar and Suresh Bhojraj developed RP-HPLC
method for simultaneous estimation of Ambroxol Hydrochloride and Loratidine in
pharmaceutical formulation. Research J. Pharm. and Tech.2008 Oct-Dec;1(4):366369
14. K Basavaiah and V S Charan, Spectrophotometric determination of Astemizole
and Loratadine based on charge-transfer complex formation with chloranilic acid.
ScienceAsia 2002;28:359-364
15. Georgeta Pavalache,, Vasile Dorneanu and Antoanela Popescu, validation of UV
molecular absorption spectrophotomertric method for Loratadine determination.
Ovidius University Annals of Chemistry 2010;21(2): pp157-162,
16. Ilangovan
Ponnilavarasan,Chebrolu.Sunil
Narendrakumar,
and
P.Asha
simultaneous estimation of Ambroxol hydrochloride and Loratadine in tablet
dosage form by using UV spectrophotometric method.,Int J Pharma and Bio
Sciences,2011 Apr-Jun;2(2):338-344
17. F.J. Rupe´rez, H. Ferna´ndez, C. Barbas.LC determination of Loratadine and related
impurities. J. Pharm. Biomed. Anal.2002; 29:35–41
18. Radhakrishna T., Narasaraju A.,Ramakrishna M.,Satyanarayana studied high
performance
liquid
chromatography
(HPLC)
and
second
derivative
spectrophotometry for the simultaneous determination of Montelukast and
Loratadine in pharmaceutical formulations.J Pharma Biomed Anal 2003;31:359368
9.0
SIGNATURE OF THE CANDIDATE
10.0 REMARKS OF THE GUIDE
Solanki Meghaben Jagdishbhai
Forwarded for Approval
Dr. E.V.S. Subrahmanyam,
10.1 NAME AND DESIGNATION OF GUIDE
Professor and Head,
Dept of Quality Assurance
10.2 SIGNATURE
Dr. E.V.S. Subrahmanyam,
11.0 HEAD OF THE DEPARTMENT
Professor and Head,
Dept of Quality Assurance
11.1 SIGNATURE
12.0 REMARKS OF THE PRINCIPAL
Forwarded for approval
Dr. Ramakrishna Shabaraya A.
12.1 SIGNATURE
Principal,
Srinivas college of pharmacy,
Valachil, Mangalore