METHOD DEVELOPMENT AND VALIDATION OF

ANTI-HYPERTENSIVE DRUG(IRBESARTAN) BY USING

ANALYTICAL TECHNIQUES SUCH AS RP-HPLC &
UPLC

Under the guidance of: Presented by:

Dr. Sumanta Mondal
Associate Proffesor
GITAM Institute of Pharmacy
GITAM (Deemed to be University)
Arindam Pal
Regd. No.: 121825201011
M.Pharmacy(MPA)
GITAM Institute of Pharmacy
GITAM (Deemed to be University)
1
 CONTENTS
• Aim and Objective

• Plan of work

• Drug profile

• Litreture Work

• Conclusion

• References

2
 AIM AND OBJECTIVE
Aim of the proposed work

• To develop and validate the estimation of anti-hypertensive drugs in

pharmaceutical dosage forms by analytical techniques such as RP-HPLC and

UPLC.

Objective of the proposed work

• To develop new, simple, accurate and reproducible method for the

multicomponent estimation of antiviral and anticancer drugs by RP-HPLC

and UPLC.

• To validate the developed method in accordance with ICH guidelines.

3
 PLAN OF WORK
The plan of the proposed work includes the following steps:

• The extensive survey of literature for drugs

• To undertake solubility studies for the drug for analysis.

• Selection of suitable solvent.

• Development of suitable mobile phase.

• Selection of suitable detection wavelength

4
DRUG PROFILE

IRBESARTAN
 IRBESARTAN
• IUPAC name :- 2-butyl-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]-
1,3-diazaspiro[4.4]non-1-en-4-one.
• Molecular formula:-C25H28N6O
• Colour:-Crystals from 96% ethanol
• Solubility:-Practically insoluable in water; Slightly soluble in
alcohol, methylene chloride.
• Drug Class:-Angiotensin II Receptor Antagonists.
• Molecular weight:-428.5g/mol
• Melting point:-180-181°C
• Storage conditions:-Keep container tightly closed in a dry and well-
ventilated place. Recommended storage temperature: 2 - 8 °C.
 DRUG PROFILE CONTD.
• Pharmacodynamics:-It has a long duration of action as it is usually taken once
daily and a wide therapeutic index as doses may be as low as 150mg daily but
doses of 900mg/day were well tolerated in healthy human subjects.
• Mechanism of action:- Irbesartan is an Angiotensin 2 Receptor Blocker. The
mechanism of action of irbesartan is as an Angiotensin 2 Receptor Antagonist
• Absorption:- Irbesartan is 60-80% bioavailable with a Tmax of 1.5-2
hours.Taking irbesartan with food does not affect the bioavailability.
• Volume of distribution:- The volume of distribution of irbesartan is 53-93L.
• Metabolism:- Irbesaran is largely metabolized by glucuronidation and
oxidation in the liver.
• Elimination:- 20% of a radiolabelled oral dose of irbesartan is recovered in
urine and the rest is recovered in the feces.<2% of the dose is recovered in
urine as the unchanged drug.
• Halflife:- The terminal elimination half life of irbesartan is 11-15 hours.
 INTRODUCTION
• Irbesartan is a medication used to treat high blood pressure,heart failure &
diabetic kidney diseases. It is a reasonable initial treatment for high blood
pressure. It is taken by mouth.
• Common side effects include dizziness, diarrhea, feeling tired, muscle pain,
and heartburn.
• Serious side effects may include kidney problems, low blood pressure,
and angioedema.
• Use in pregnancy may harm the baby and use when breastfeeding is not
recommended.
• Irbesartan was patented in 1990 and approved for medical use in 1997.
• In 2016, it was the 171st most prescribed medication in the United States,
with more than 3.6 million prescriptions
• .
LITERATURE REVIEW.
 UV METHODS.
METHODS REFERENCE SOLVENTS LINEARITY RANGE

UV Method-1 Kishanta Kumar Methanol 246nm

Pradhan et al

UV Method-2 Piusha Shakya et Methanol 224nm

al
 HPLC METHODS
METHOD SOLVENTS/ COLUMN WAVELENGTH REFERENCE
MOBILE PHASE

RP-HPLC Acetonitrile Hypersil BDS 202nm R. A. Mhaske et

Method 1 al

RP-HPLC Mixture of Hypesil BDS 260nm B.Raja et al

Method 2 sodium acetate
buffer:
acetonitrile
(45:55v/v).
RP-HPLC Mixture of Hypersil pack 260nm M.M.Eswarudu
Method-3 sodium acetate BDS et al
buffer:
acetonitrile
(45:55v/v).
 Plan of work

 To undertake solubility studies of Irbesartan.

 To develop new UV Spectrophotometric and RP –
HPLC methods for Irbesartan in API.
 To validate the developed UV Spectrophotometric and
RP-HPLC methods as per ICH guidelines.
 To study the stability indicating aspects of the
developed RP-HPLC method.
 REFERENCES
• Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, Ritz E, Atkins
RC, Rohde R, Raz I: Renoprotective effect of the angiotensin-receptor antagonist
irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001
Sep 20;345(12):851-60. [PMID:11565517]

• Adams MA, Trudeau L: Irbesartan: review of pharmacology and comparative

properties. Can J Clin Pharmacol. 2000 Spring;7(1):22-31. [PMID:10822210]

• Croom KF, Curran MP, Goa KL, Perry CM: Irbesartan: a review of its use in
hypertension and in the management of diabetic nephropathy. Drugs.
2004;64(9):999-1028. [PMID:15101793]

• Method Development, Validation and Stability Study of Irbesartan in Bulk and

Pharmaceutical Dosage Form by UV-Spectrophotometric Method Kishanta Kumar
Pradhan*1, Uma Shankar Mishra1, Subasini Pattnaik2,Debananda Mishra1,
Ghanshyam Panigrahi1, Kanhu Charana Sahu.
 CONTD.
• SIMULTANEOUS ESTIMATION OF IRBESARTAN AND HYDROCHLOROTHIAZIDE BY UV
SPECTROSCOPY PIUSHA SHAKYA1*12 , PUSHPENDRA KUMAR JAIN, S. P.
SHRIVASTAVA, ASMITA GAJBHIYE.

• RP-HPLC METHOD FOR SIMULTATANEOUS DETERMINATION OF IRBESARTAN,

LOSARTAN, HYDRO-CHLOROTHIAZIDE AND CHLORTHALIDONE–APPLICATION TO
COMMERCIALLY AVAILABLE DRUG PRODUCTS . R. A. Mhaske*1, S. Sahasrabudhe 1 and A.
A. Mhaske 1

• RP-HPLC Method for the Simultaneous Estimation of Irbesartan and Hydrochlorthiazide in

Pharmaceutical Dosage Form .B. Raja,Potru Himasri, Bantu Ramadevi

• RP-HPLC Method Development and Validation for Simultaneous Estimation of Irbesartan and
Hydrochlorothiazide in Pharmaceutical Dosage Form M.M. Eswarudu, T. Narendra Chary1, Sunil
Junapudi1, M. Sushma.

• Wikipedia
THANK YOU