Process Validation for Atenolol Tablet Dosage Form

‘‘PROCESS VALIDATION FOR ATENOLOL TABLET DOSAGE FORM’’

DISSERTATION PROTOCOL

SUBMITTED TO

RAJIVGANDHIUNIVERSITY OF HEALTH SCIENCES

BANGALORE, KARNATAKA.

BY

MARJADI NIRMAL BHUPESHBHAI

B.PHARM,

UNDER THE GUIDANCE OF,

DR. SURESH D.

PROFESSOR.

DEPARTMENT OF QUALITY ASSURANCE,

SHREE DEVI COLLEGE OF PHARMACY

MANGALORE – 574 142

(2010-2012)

RAJIVGANDHIUNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA.

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. / NAME OF THE CANDIDATE
AND ADDRESS (IN BLOCK LETTERS) / MARJADI NIRMAL BHUPESHBHAI
A/102, INDRAHARSH APARTMENT,
MOTI MEHTWAD,VALSAD-396 001,
GUJARAT.
2. /

NAME OF THE INSTITUTION

/ SHREE DEVI COLLEGE OF PHARMACY,
AIRPORT ROAD, KENJAR VILLAGE,
MALAVOOR PANCHAYAT,
MANGALORE -574 142
KARNATAKA.
3. /

COURSE OF STUDY AND SUBJECT

/ MASTER OF PHARMACY IN
QUALITY ASSURANCE
4. / DATE OF ADMISSION OF COURSE / NOVEMBER- 2010
5. /

TITLE OF TOPIC :- ‘‘ PROCESS VALIDATION FOR ATENOLOL TABLET

DOSAGE FORM”
6.
6.1
6.2
6.3
7.
7.1
7.2
7.3
7.4
8. / BRIEF RESUME OF THE INTENDED WORK:
NEED FOR THE STUDY:
Cardiovascular Diseasesare the class of diseases that involve the heart or blood vessels(arteries and veins). Most countries face high and increasing number of cardio vascular diseases. Each year heart disease kills more Americans than cancer In recent years, cardiovascular risk in women increasing and has killed more women than breast cancer.[1]
HYPERTENSIONOR HIGH BLOOD PRESSUREis a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. It is the opposite of hypotension. Hypertension is classified as either primary (essential) hypertension or secondary hypertension; about 90-95% of cases are termed “primary hypertension” ,
which refers to high blood pressure for which no medical cause has been found. The remaining 5-10% of cases (secondary hypertension) are caused by other conditions that affects the kidneys, arteries, heart or endocrine system.
Persistant hypertension is one of the risk factor for stroke, myocardial infarction, heart failure and arterial aneurysm, and is a leading cause chronic of kidney failure. Moderate elevation of arterial blood pressure leads to shortened life expectancy .Diet and lifestyle can improve blood pressure control and decrease the risk of blood pressure and associated health complications, although drug treatment may prove necessary in patients for whom life style changes prove ineffective or insufficient.[2]
ATENOLOLis a selective β receptor antagonist, a drug belonging to the group of beta blockers, a class of drugs used primary in cardio vascular diseases. Introduced in 1976, atenolol was developed as a replacement for propranolol in the treatment of hypertension. The chemical works by slowing down the heart and reducing its workload. Unlike propranolol, atenolol does not pass through the blood brain barrier thus avoiding central nervous system side effects.[3]
Atenolol is used alone or in combination with other medications to treat high blood pressure. It is also used to prevent angina (chest pain) and improve survival after a heart attack. Atenolol is in a class of medications called beta blockers. It works by relaxing blood vessels and slowing heart rate to improve blood flow and decrease blood pressure.[4]
PROCESS VALIDATIONis establishing, through documented evidence, a high degree of assurance that specific process will consistently produce a product that meets its predetermined specifications and quality characteristics.[5]
There is no specific process validation method reported for atenolol. Hence, investigation of new process validation method is in need for the process validation for atenolol, in pharmaceutical dosage form.
REVIEW OF LITERATURE :
chemically atenolol is (RS)-2-{4-[2-hydroxy-3(propan-2-ylamino)propoxy]
phenyl]acetamide and molecular formula is C14H22N2O3 and molecular weight is 266.336g/mol. [3] It is soluble in ethanol/methanol. [6]

[ATENOLOL]
Venkata RT, et al., developed Process Validation of Citalopram Hydrobromide Tablets ,Validation is found on, but not required by regulatory departments and is bestviewed as an impartment and integral part of cGMP. Validation is therefore one element of quality assuranceprograms associated with a particular process. Then word validation simply means “assessment of validity” or action of proving effectiveness. This process involves addition of granulating agent to the dry mixed materialand converting into granules .The goal of quality system is to consistently produce products that are suitablefor their intended use. Process validation is a key element in assuring that these principles and goals are met.[7]
Rohokale BS, et al., developed studiesin process developmentof Metformin HCl tablet dosageformulation,Process development batches (PDB) were taken and evaluated for satisfactory result during sifting, dry mixing, preparation of granulating agent, wet mixing, wet milling, drying, sizing, lubrication and compression. Process development parameter with respect to ruggedness and robustness of manufacturing process were evaluated by trial and error methods. Process development batch PDB1 wastaken as per R & D guidelines and evaluated for satisfactory result. Due to unsatisfactory results, changes was done PDB2, in quantity of granulating agent and processing stage. Process development parameter of PDB2 were evaluated & found satisfactory for production run.[8]
Rohokale BS, et al., developedstudies in process development ofnimusulide 100 mg tablet dosage formulation Process development batches (PDB) were taken and evaluated for satisfactory result during sifting, dry mixing, preparation of granulating agent, wet mixing, drying, sizing, lubrication and compression. Process development stage parameter with respect to ruggedness and robustness of manufacturing process were evaluated by trial and error methods. Process development batch PDB1 was takenas per R & D guidelines and evaluated for satisfactory result. Tablet lamination was reported during compression of PDB1, due to excessive moisture content. Hence drying time and inlet air drying time was increased . This changes was done in PDB2 and batch was taken as per same manufacturing process. In orderto develop rugged and robust PDB3 was taken as per same manufacturing process. Result obtained fromPDB2 and PDB3 was shows that the manufacturing process as well as formulation was found satisfactory for production run.[9]
Devi NK et al., developed process validation of Galantamine hydrobromide tablets, Here the validation of critical steps during manufacturing such as blending, compression, coating and dissolution was done for Galantamine hydrobromide tablets with the support of process validation protocol.[10]
Jena S et al., developed industrial process validation for solid dosage forms.
Here this article concentrates on the process validation of solid dosage forms,
protocol preparation and regulatory basis for process validation with special
emphasis on tablets in industry. It gives in detail the validation of each step of
the manufacturing process through wet granulation.[11]
Marjo-riitta H., developed a literature review of pharmaceutical process validation, The advantages and disadvantages of process validation have never been systematically evaluated, and validation is frequently performed without a real understanding of the work involved. The challenge for the pharmaceutical industry is to streamline and/or simplify validation without sacrificing product quality.[12]
Ted Buyers of Food & Drug Administration, “Food & Drug Administration expects the industry tobuild quality into the product” Food & Drug Administration requires the validation to be completed even atthe time of applying for approval any piece of equipment, facility or process operatedunder Current Good Manufacturing Practices should be validated.[13]
OBJECTIVES OF THE STUDY:
Review of literature revealed that there is no specific method reported for the process validation of Atenolol in pharmaceutical dosage form.
Hence the goals of the present work are
The manufacturing process, in addition to the individual equipment, must be validated.
The goal is to create a robust manufacturing process that consistently produces a drug product with minimal variation that adheres to quality criteria of purity, identity, and potency.
A validation plan for the manufacturing process should be drafted and executed by engineers in order to satisfy guidelines.
Just as equipment validation, major changes after the initial validation will result in the need for subsequent revalidation.
In the end, process validation will ensure a robust product that is highly reproducible over time.
MATERIALS AND METHODS:
Materials
Drugs and excipients as needed for the specific pharmaceutical formulation under study.
Source of data:
Data will be obtained from Science Direct, and other internet facilities, literature search and related articles from library of Shree Devi College of Pharmacy, Digital Library of RGUHS, Bangalore, etc.
Journals
Asian Journal of Research in Chemistry
International Journal of chem. Tech Research
Journal of young Pharmacists
Indian Journal of Pharmaceutical Science
International Journal of Pharmacy and Pharmaceutical Science
Journal of Pharmacy Research
Text Books and Pharmacopoeia

• Josepd D. Nally, Good Manufacturing For Pharmaceuticals, 6thed.
• PD Sethi, Quantitative Analysis of Drugs in Pharmaceutical Formulation,

3rded. Delhi: CBS Publisher and Distributors

• WHO Good Manufacturing Practices And Inspection (Quality Assurance Of Phamaceuticals)
• Robert A. Nash, Alfred H. Wachter, Pharmaceuticals Process Validation, 3rded.

Copyright 2003 by Marcel Dekker, Inc.

• Stephen W. Hoag, Larry L. Augsburger, pharmaceutical dosage forms : tablets, 3rded.
• The Indian Pharmacopoeia, Government of India, Ministry of Health and Family Welfare, Published by The Indian Pharmacopoeia commission Gaziabad, Volume 2, 2007

Internet Browsing
MethodofCollectionofData (IncludingSampling Procedures, IfAny)
Data will be collected from process validations carried out on the different stages of tablet manufacture like Sifting or Pulverization, Granulation, Drying, Compression, Packaging and Finished product testing.
The following parameters will be consider as a process parameter.
Processing stage / Process parameters
Sifting / Sieve integrity
Dry Mixing / Speed of Mixer
Mixing Time
Granulation
[Wet mixing] / Speed of Mixer & chopper
Mixing Time
Total quantity of solvent used
Drying of wet granules / Inlet air temperature
Drying time
Blending & Lubrication / Mixing time
Speed of the blender
Compression / Speed of compression
Pre-compression force (if applicable)
Compression force
Primary Packing
[Blister Packing] / Machine speed,
Sealing & forming temperatures
Primary Packing
[Strip Packing] / Machine speed,
Sealing temperature
Primary Packing
[Container Packing] / Type of filling (manual / auto)
Power value (in %) of the induction sealing machine
The Intermediate dosage form will be evaluated for moisture content or LOD of dried granulation, granulation particle size distribution, blend uniformity, Bulk Density, Angle of repose etc.
The finished product will be analyzed for appearance, Dimensions, individual tablet weight, assay, content uniformity, friability, tablet hardness, tablet thickness and disintegration time, dissolution.
This will be followed by statistical analysis of data obtained using tools like Standard deviation, Relative standard deviation, comparision in Chart form, Tolerance limit, ANOVA etc.
Does the study require any investigation or intervention to be conducted on patients or other humans or animals? If so, please mention briefly.
- NOT APPLICABLE -
Has ethical clearance been obtained from your institution in case of 7.3?
- NOT APPLICABLE-
LIST OF REFERENCES:
1) date 2011April24).
2) date 2011April24).
3) ,(access date 2011April24).
4) 2011April24).
5) date 2011April24).
6) date 2011April24).
7)Venkat RT, Kotta KK, Leela M, Rao K, Sasaikanth K. Process validation of citalopram hydrobromide tablets.International Journal Of Research in Pharmaceutical And Biomedical Sciences.2010 Oct – Dec;1(2):109-23.
[
8)Rohokale BS, Jadhav VM, Kadam VJ.Studies in process development of metformin hcl tablet dosage formulation. International Journal Of Pharmacy And Pharmaceutical Science.2010 July;2(4):80-2.
[
9) Rohokale BS, Jadhav VM, Kadam VJ.studies in process development of
nimusulide 100 mg tablet dosage formulation. International Journal Of Pharmtech
Research.2010 Oct-Dec;2(4):2441-44.
10) Devi NK, Reddy VV, Mrudula BS and Madhavi BR. Process validation of
galantamine hydrochloride tablets.Research Journal Of Pharmaceutical Dosage
Form And Technology (RJPDFT).2010 January – February;2(1):189.
[
11) Jena S, Arjun G, Anil kumar RNV, Satish kumar D, Vinod KR, David B.
industrial process validation of solid dosage forms – an overview.International
Journal Of Pharmaceutical Sciences Review And Research.2010 September –
Octber;4(2)(25):145-54.
[
12) Marjo-Riitta H, Jouko Y, Jakka-Pekka M. A literature review of pharmaceutical
process validation.Pharmaceutical Technology Europe.2003 March1.
[
Review-of- Pharmaceutical-Process-Vali/ArticleLong/Article/detail/52258]
13) U.S. FDA. Guidelines on general principles of Process Validation;1987 May.
9. / Signature of the candidate / (MARJADI NIRMAL BHUPESHBHAI)
10. / Remarks of the Guide
‘‘PROCESS VALIDATION FOR ATENOLOL
TABLET DOSAGE FORM’’. To carried out by Mr. Marjadi Nirmal B. of M.pharm has been discussed and worked out under my direction and supervision as an official guide. The project work envisaged is of great importance in the field of process validation. The work can be carried out in Quality Assurance laboratory of Shree Devi College Of Pharmacy for which facilities are available. Hence the project is viable and recommended for clearance and approval.
11. / Name & Designation of
(in block letters)
11.1Guide / DR. SURESH D.
Department of Quality Assurance.
Shree Devi College Of Pharmacy,
Airport Road, Kenjar Village,
Malavoor Panchayath,
Mangalore, 574 142,
Karnataka.
11.2 Signature
11.3 Head of the department / DR. SURESH D.
Department of Quality Assurance.
Shree Devi College Of Pharmacy,
Airport Road, Kenjar Village,
Malavoor Panchayath,
Mangalore, 574 142,
Karnataka.
11.4 Signature
12. / 12.1 Remarks of Principal
The Programme and the Research work that is undertaken by Mr. Marjadi Nirmal B. has potential implication in the field of Quality Assurance. The work can be carried the Research Laboratory of Quality Assurance department at Shree Devi College of Pharmacy. Hence the project is recommended and requested for the clearance and approval.
12.2 Signature

1