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Research guide

Department of quality assurance

Government College of Pharmacy, Amravati

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 CONTENTS
INTRODUCTION LITERATURE
REVIEW
AIM,
OBJECTIVE & Drugs Profile
Scope PLAN OF WORK

BIBLIOGRAPHY

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 INTRODUCTION
The “Stability” of a drug dosage form refers to the ability of a
particular formulation, in a specific container, to maintain it’s
physical, chemical, therapeutic and toxicological
specification presented in the monograph on its identity,
strength, quality, and purity
Stability testing is an important part of the process of
drug product development. The stability of a drug product or
a drug substance is a critical parameter which may affect
purity, potency and safety.
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Degradation studies are carried out for the
following reasons:
• To develop and validate a stability indicating
method.
• To determine degradation pathways of drug
substances and drug products (e.g., during
development phase).
• To identify impurities related to drug substances or
excipients.
• To understand the drug molecule chemistry.
• To generate more stable formulations.
• To generate a degradation profile. 4
Conditions generally employed for force
Degradation:
Experimental
Degradation type Storage condition Sampling time.
condition
Hydrolysis 0.1N HCL 400c 600c 1,3,5 days
0.1N NaOH 400c 600c 1,3,5 days
PH 2,4,6,8. 400c 600c 1,3,5 days
Oxidative 3% H2O2 25oc 400c 1,3,5 days
Azo-bis-iso-butyro-
25oc 400c 1,3,5 days
nitrile
Photolytic Light 1x ICH NA 1,3,5 days
Light 3x ICH NA 1,3,5 days
Thermal Heat chamber 600c 1,3,5 days
Heat chamber 600c 5 1,3,5 days
Heat chamber 800c 1,3,5 days
 Types of Stability indicating Assay methods:
1.Specific stability indicating Assay method: -
It is a method that is able to measure unequivocally the drug in the
presence of all degradation products, in the presence of excipients
and additives which are expected to be present in the formulation.

2.Selective stability indicating Assay method: -

It is method that is able to measure unequivocally the drugs and all
degradation products in the presence of excipients and additives
which are expected to be present in the formulation.

3.Development and validation of Stability indicating assay

methods:-
• Step 1: Critical study of drug structure to assess the likely
decomposition route. 6
• Step 2: Collection of information of Physicochemical
Parameters.

• Step 3: Force decomposition Studies.

• Step 4: Preliminary separation studies on stressed

samples.

• Step 5: Final method development and optimization.

• Step 6: Identification and characterization of degradation

products and preparation of standards.

• Step 7: Validation of stability indicating Assay method.

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DRUG PROFILE:-
Domeperidone:

IUPAC Name:-5-chloro-1-(1-[3-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-
yl)propyl]piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one

Category:- Anti-Emetics.

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Esomeprazole:

IUPAC Name:- (S)-5-Methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-

yl)methylsulfinyl]-3H-benzoimidazole.

Category:- Proton Pump inhibitor.

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Pantaprazole:

IUPAC Name:- (RS)-6-(Difluoromethoxy)-2-[(3,4-dimethoxypyridin-

2-yl)methylsulfinyl]-1H-benzo[d]imidazole

Category:- Proton Pump inhibitor.

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 LITERATURE
REVIEW
V S Janardhanan et al: (2010)

HPLC method has been developed and subsequently validated for the
simultaneous determination of pantoprazole and domperidone in
commercial tablets. The proposed HPLC method utilizes Phenomenex
Gemini C18 column (150 mm _ 4.6 mm i.d., 5 μm) and mobile phase
consisting of methanol acetonitrile-20 mM dipotassium hydrogen phosphate
and phosphoric acid buffer pH 7.0 (20:33.11:46.89, v/v/v) at a flow rate of
1.10 mL/min.Quantitation was achieved with UV detection at 280 nm based
on peak area with linear calibration curves at concentration ranges 1.0-
10μg/ml for pantoprazole and 0.5-5.0μg/mL for domperidone.
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R. K. Seshadri et al: (2012)
A gradient reversed-phase liquid chromatographic (RP-LC) method was developed for the
quantitative estimation of the pharmaceutical dosage form of esomeprazole and
Domperidone capsules. The chromatographic separation was achieved on a column
packed with octadecyl silane, having a column length of 250 mm and diameter of 4.6 mm
with a particle size of 5 μm, and by following a gradient program using a combination of
a monobasic potassium phosphate buffer (0.05M) and acetonitrile. Since the spectral
properties were similar, both compounds were estimated at 285 nm.

Balkrishna et al(2012)
Methods like Spectrophotometry, HPLC, HPTLC and LC-MS were reported for the
determination of Domperidone in combination with other drugs as well as in biological
fluids but no method has been reported for simultaneous analysis of Domperidone and
Omeprazole in its combination anywhere before. These above developed methods are too
expensive and time consuming. An attempt has been made to develop a simple,
economical, precise, accurate and reproducible HPLC method for estimation of
Domperidone and Omeprazole in bulk as well as pharmaceutical 12formulations.
A.B.N. Nagewara Rao et al(2012)
A simple reversed-phase high-performance liquid chromatographic (RP-HPLC) method has
been developed and validated for simultaneous determination of Domperidone (DOM) and
Pantoprazole(PAN) in capsules. The drugs were separated on an analytical column, HiQ Sil
C18V, 4.6mm x 250 mm, 5 μm (Kya Tech Japan). The mobile phase was a mixture of
acetonitrile and 0.05M potassium di- hydrogen phosphate buffer (pH 6.5 adjusted with
ortho phosphoric acid) in ratio of 50:50% v/v plus 0.05% TEA. UV detection was performed
at 290 nm.

Prasanna Reddy Battu :(2009)

The present work describes a simple reverse phase HPLC method for the determination of
pantoprazole and domperidone from tablet formulations. The determination was carried
out on a Hypersil, BDS, C-18 (150×4.6 mm, 5 micron) column using a mobile phase
consisting of 0.05 M, 4.70 pH, potassium dihydrogen phosphate buffer - acetonitrile
(720:280 v/v) at a flow rate and run time of 1.0 ml/min and 10 min, respectively. The
eluent was monitored at 280 nm. The method was reproducible, with good resolution
between pantoprazole and domperidone. The detector response was found to be linear in
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the concentration range of 10-60 μg/ml for pantoprazole and 5-30 μg/ml for domperidone.
Vandana B.Patel et al :( 2011)
Simple, accurate and precise first derivative zero crossing spectrophotometric method has
been developed for simultaneous determination of domperidon and esomeprazole
magnesium in pure and commercial formulation without any prior separation or
purification. The linearity range was found to be 3-12 μg ml-1 for both the drugs. The
value of limit of detection and limit of quantification was 0.1674 μg ml-1 and 0.558 μg ml-
1 for domperidone and 0.0454 μg ml-1 and 0.151 μg ml-1 for esomeprazole magnesium
respectively.

Rajnish Kumar et al :( 2011)

A simple and sensitive spectrophotometric method has been described for the assay of
pantoprazole either in pure form or in pharmaceutical solid dosage form.Absorption
maxima of Pantoprazole in water were found to be at 292 nm. Beer’s law is obeyed in the
range 5-70 μg/mL. Result of percentage recovery and placebo interference shows that the
method was not affected by the presence of common excipients. The percentages assay of
Pantoprazole in tablet was more than 99%. The method was validated by determining its
sensitivity, accuracy and precision which proves suitability of the developed method for
the routine estimation of pantoprazole in bulk and solid dosage form.
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AIM, OBJECTIVES AND
SCOPE:

AIM:
Development of stability indicating assay method for antiemetic drugs in combined
dosage form.

OBJECTIVES:
Analysis is important in every product but it is vital in medicines as it involves life. The
assurance of quality is achieved through analysis of drug product. The analytical
chemistry has number of challenges in developing methods for their analysis with the
number of analytical techniques which are available for the estimation drugs and their
combination.
The objective of present study is:
 To simultaneously estimate the component of anti-emetic drug in dosage form.
 To develop stability indicating assay method of anti-emetic drug.
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SCOPE:

Method developed can be conveniently used Routine determination of

drug in pharmaceutical preparation in pharmaceutical industry.
Comparative estimation of different branded products may be coincide
one.
The Proposed method could be employed for the stability studies on
Pharmaceutical preparations within Pharmaceutical industry. The
objective of the present study is framed on the basis of literature review
and preliminary evaluation it can be changed specially drugs selected and
chromatograph conditions as per the need and requirement of the study.

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 PLAN OF WORK

 Literature survey.

 Procurement of reference standards.

 Assay of drugs.

 Evaluation by spectroscopy technique.

 Development of chromatographic method.

 To conduct force degradation studies/ stability study of product.

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 BIBLIOGRAPHY
• Raja Kumar, Thummala Veera, Ivon Elisha, “ A Single Gradient Stability-Indicating
Reversed-Phase LC Method for the Estimation of Impurities in Omeprazole and
Domperidone Capsules”, Sci Pharm. 2013; 81: 437–458.

• Vaithiyanathan Sree Janardhanan, Rajappan Manavalan and Kannappan Valliappan,

“Stability-indicating HPLC method for the simultaneous,determination of
pantoprazole, and domperidone from their combination dosage forms” , Int. J. Drug
Dev. & Res., Oct-Dec 2011, 3 (4): 323-335.

• Sunil Singh, Jyoti Rai, Inamullah, Nisha Choudhary, “Stability Indicating Simultaneous
Equation Method for Determination of Domperidone and (S)-Esomeprazole in Capsule
Dosage Form Using UV-Spectrophotometer, British Journal of Pharmaceutical Research
3(3): 435-445, 2013.

• Jitendra Kumar, M.S. Charde, A.S. Welankiwar and R.D Chakole: “Development of
forced degradation studies of drugs” , International Journal 18of Advances in
Pharmaceuticals,vol 2 (3) 2013, pageno 35-38.
• www.ncbi.nlm.nih.gov/m/..

• Rajnish Kumar, Harinder Singh and Pinderjit Singh, “ Development of UV

Spectrophotometric method for estimation of Pantoprazole in pharmaceutical dosage
forms”, J. Chem. Pharm. Res., 2011, 3(2):113-117.

• Sagar Solanki, Anandkumari Captain and Vandana B.Patel, “Simultaneous

determination of Domperidone and Esomeprazole magnesium in Pharmaceutical
Capsule Formulation by Derivative Spectrophotometric Method”, Int.J. ChemTech
Res.2011,3(4).

• Balkrishna et al “Method development and the simultaneous determination of

omeprazole and domeperidone in solid dosage form by RP-HPLC”,Int J Pharm Pharm
Sci, Vol 4, Suppl 5, 109-114.

• G.Srinivasa Rao, A.B.N.NagewaraRao, G. Rohini Reddy, “RP-HPLC method for

simultaneous estimation of domperidone and pantoprazole in capsule dosage form”,
Der Pharmacia Lettre, 2012, 4 (6):1712-1720.
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• Prasanna Reddy, “Simultaneous HPLC Estimation of Pantoprazole and Domperidone
from Tablets”, Int.J. ChemTech Res.2009, 1(2).

• Sohan S. Chitlange, Amir I. Mulla, Ganesh R. Pawbake and Sagar B. Wankhede,“ A

validated RP-HPLC method for simultaneous estimation of Dexrabeprazole and
Domperidone in pharmaceutical dosage form”, Der Pharmacia Sinica, 2010, 1 (1):42-47.

• Shodhganga, “Simultaneous determination of Omeprazole and Domperidone impurities in

active pharmaceutical ingredients by UPLC”,
shodhganga.inflibnet.ac.in/bitstream/10603/12745/.../10.

• P. Sriniwas, T shiva rao, “Validation for the simultaneous analysis of related substances of
omeprazole and domperidone active pharmaceutical ingredient”, Int J Pharm Bio Sci
2013 Apr; 4(2): (P) 906 – 911.

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