Download Name of the institution

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
BANGALORE,KARNATAKA.
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
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Name of the candidate and address
K. NAVEEN
PERMANENT ADDRESS
S/O K.SUNDARA RAJA GUPTA
BAZAR STREET, BHAKARAPET (P.O),
CHITTOOR(D.T), ANDHRA PRADESH.
2
Name of the institution
KRUPANIDHI COLLEGEOF
PHARMACY,
Chikka Bellandur,
Carmelaram Post,
Varthur Hobli,
Bangalore – 560035
3
Course of study and subject
MASTER OF PHARMACY IN
PHARMACEUTICS
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Date of the admission
JUNE 2009
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Title of the topic:
“DEVELOPMENT AND EVALUATION OF
VOGLIBOSE TABLETS ”
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6.
Brief resume of the intended work:
6.1 Need for the study:
Presently, there are about 150 million diabetic patients worldwide, out of which 33
million are in India alone. As per WHO estimates, the number of diabetics worldwide would
increase to 300 million by 2025, with India will become the Diabetes capital of the world.1
The delivery of drugs for management of Diabetes in solid oral dosage forms is
desirable from both economic and compliance point of view. These drugs have the capacity to
improve the quality of patient life substantially.
α- glucosidase inhibitors are oral anti-diabetic drugs. These drugs are competitive
inhibitors of the intestinal α- glucosidases and reduce post meal excursions by delaying
digestion and absorption of starch and disaccharides.2 Their mechanism of action being limited
to the intestinal brush border membrane, and owing to their structural features, they have
limited systemic bioavailability, due to which they have much reduced side-effect profile
compared to contemporary antihyperglycemic drugs. A large section of people are diagnosed
to be suffering from pre-diabetes condition (such as obesity) and to treat that condition alphaglucosidase inhibitors is widely prescribed.
There are currently three drugs which belong to this class - acarbose, miglitol and
voglibose, of which voglibose is the newest. Voglibose scores over both acarbose and miglitol
in terms of lower side effects profile.3 Voglibose is 20 to 30 fold more potent competitive
inhibitor of intestinal alpha-glucosidase than acarbose. Beneficial effects of voglibose have
been demonstrated both in human and rodents with diabetes.4 The drug has been clinically
used to improve glucose tolerance by inhibiting digestion and absorption of glucose from the
intestine without promoting insulin secretion.
In diabetic patients, post-prandial impaired glucose tolerance (IGT) level is
observed leading to hyperglycemia. To reduce hyperglycemia and IGT, voglibose tablets can
be used. These tablets release their medicaments in intestine and act locally to avoid the
hyperglycemia by competitively binding with the disaccharidases in intestine and the activity
will become low and through these events patient compliance is improved.
The oral route is a route of choice for the patients because they are effective and
self medication is possible. Solid oral dosage forms utilize relatively inexpensive technology
and are compact and their appearance can be modified to create brand identification and
patient compliance.
They are usually available in various formulations such as tablets,
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capsules and powders. In the preparation of tablets, based on the drug, different excipients are
selected by performing various preformulation studies. It is always a challenge to develop lowcost non-patent infringing formulations for the generic market.
Therefore, in the present investigation, an attempt will be made to develop a patent
non-infringing generic formula of a tablet of α-glucosidase inhibitor (voglibose) and
characterize the product using appropriate evaluation parameters.
6.2 Objectives of the study:
The primary aim of the proposed project is to develop voglibose tablets. In order to
fulfill the aim, the following objectives have to be achieved:
1. Preformulation studies for selection of suitable excipients to develop a suitable tablet
based on physicochemical properties of drug and excipients.
2. Screening of excipients to check compatibility and efficacy for developing
the tablets.
3. Formulation development of the Tablet dosage form
4. Study of pre-compression parameters of the formulation.
5. Evaluation of compressed products, identification and troubleshoot compression defects,
if any.
6. Optimizing the product to comply with official specifications / standards.
7. Study the stability of the formulation as per ICH guidelines.
6.3 Review of the literature:
Oral route is the most suitable method of administering the drugs for systemic
effect. It is the preferred route for most therapeutic agents owing to its patient acceptance;
convenience of administration, cost-effective manufacturing and most importantly it does not
require sterile processing and generally have long shelf life. The tablets are perhaps the
simplest, most common and most economical method of processing an active agent into a drug
delivery product.5,6 Tablets are sufficiently resistant to shock and abrasions to withstand
handling during manufacturing / packaging / transport. As the tablets are unit dosage form
they together offer greatest capabilities of all oral dosage form for the greatest dose precision
and least content variability. The unit cost is lowest as compared to all other dosage forms,
well situated for large-scale production and easiest, cheapest to package and ship. They
provide the greatest ease of swallowing with the least tendency to hang up above the stomach.6
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The solid oral dosage forms have to be analyzed regularly for their in vitro
performance as per official and un-official methods such as assay, weight and content
uniformity, size, shape, color, hardness, disintegration, dissolution, etc. following
pharmacopoeial or drug authority recommendations and ensuring GMP compliance at each
stage of production and testing .7,8
The generic formulations should be non-patent infringing with respect to excipients,
their quantities and manufacturing methodologies and hence need considerable intellectual
inputs from the formulators to arrive at the best possible formulation which could be accepted
by the drug authorities. Further, the formulations should comply with standards and safety
specifications of the regulated market for which it is intended. In the formulation of the generic
products, the formulator mainly aims to match the dissolution profile of the generic product
with the innovator product by in vitro release studies or otherwise prove the bioequivalence of
the product compared to the innovator brand or (Reference Listed Drug) RLD product. For
suitable category of drugs there may be bio-waiver, and hence a huge savings on the part of the
sponsor company.9
In addition, the growth of the pharmaceutical industry as well as increased
competition from both foreign and domestic markets require that a tablet manufacturer have
greater concern regarding the economics of tablet production by introducing the less laborintensive, higher productive manufacturing methods for making the increasing number of
tablet products available today .10
Type 2 diabetes accounts for 90% to 95% of all known cases of diabetes. Although it
normally occurs among older, inactive individuals, children and adolescents are increasingly
identified, contributing to the growing pool of patients who require lifelong care. Progressive
in nature, type 2 diabetes begins with peripheral insulin resistance and ends in complete loss of
insulin secretion if the disease progresses through its entire natural history. Initially, pancreatic
beta cells are able to compensate for insulin resistance by increasing basal and postprandial
insulin secretion. In time, however, compensation fails as beta cells exhaust their capacity to
react appropriately to rising glucose concentrations. A deterioration of glucose homeostasis
ensues, and glucose intolerance develops. Left untreated, intolerance worsens, and the diabetic
state is manifested. 11
α- Glucosidase inhibitors are being recently used for the treatment of hyperglycemia
in patients with type 2 diabetes mellitus. These drugs can delay digestion of complex
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carbohydrates by acting locally at the small intestine as competitive inhibitors of the intestinal
glucosidase enzyme. It has been shown that these drugs in the presence of carbohydrate
administration reduce significantly the postprandial rise in plasma insulin both in nondiabetics
and in type 2 diabetic patients, an effect that is secondary to the reduced peaking in
postprandial glycemic levels. This effect is thought to be desirable because it may inhibit the
overwork of the pancreatic cells and may avoid hyperinsulinemic state probably related to
ischemic heart disease. 12
Voglibose is a valiolamine derivative.13 Voglibose is
an anti-diabetic agent and it belongs to alpha-glucosidase
inhibitors class. It competitively and reversibly inhibits the
alpha–glucosidase enzymes; glucoamylase, sucrose, etc and it
acts by delaying the digestion and absorption of sugar.
Voglibose is slowly and poorly absorbed, and is rapidly
excreted. Little metabolism occurs and no metabolites have as
Structure of voglibose
yet been found .Voglibose should be administered in
conjunction with diet treatment or diet plus a sulfonylurea. Some investigators recommend the
use of voglibose only in patients who achieve satisfactory fasting glucose level.14
The predicted water solubility of voglibose is 1.90 x 102 mg/ml, calculated using
ALOGPS.15
The inhibition power of voglibose on alpha-glucosidase is evaluated by performing an
inhibition assay in an Enzyme-Immobilized amino-microplate.16
The determination of
voglibose in pharmaceutical tablets is performed with a highly sensitive liquid
chromatographic procedure with post-column derivatization using fluorescence detection (LCFD).17
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Materials and methods:
7.1 Source of data:
Data will be obtained from drug bank, rxlist, Pubmed, Science Direct, Medline, US
patent office website and other Internet facilities, literature search, and related articles from
library of Krupanidhi College of Pharmacy and Bal Pharma ltd..
7.2 Method of collection of data (including sampling procedures if any):
Data on drugs will be collected from drug information center, standard books,
physicochemical database, and literature search. Extensive Preformulation trial provides the
basis of selecting the excipients and system for final formulation development. The precompression studies include the particle size, adhesion and cohesion of particles, wettability,
moisture content and hygroscopicity, effect of lubricants and adhesives. The post compression
parameters include identification of defects in the tablets, weight variation, content uniformity,
friability, Disintegration, dissolution studies.
7.3 Does the study require any investigation or interventions to be
Conducted on patients or other humans or animals?
No.
7.4 Has ethical clearance been obtained from your institution in case of 7.3?
Not Applicable
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List of References:
1. http://www.medicalnewstoday.com/articles/36827.php [Access date : 2009 Nov 27]
2. Nolte MS. Pancreatic Hormones & Antidiabetic Drugs. In: Katzung BG, Masters
SB, Trevor AJ, editors. Basic and clinical pharmacology. 11th ed. New Delhi: Tata
McGraw Hill Education Private Limited; 2009. p. 742-4.
3. http://en.wikipedia.org/wiki/Voglibose [Access date : 2009 Nov 27]
4. Yasuda K, Shimowada K, Uno M, Odaka H, Adachi T, Shihara N et al. Longterm therapeutic effects of voglibose, a potent intestinal alpha-glucosidase inhibitor,
in spontaneous diabetic GK rats. Diabetes Res Clin Pract 2003;59(2):113-22.
5. Speers M, Bonnano C. Economic aspects of controlled drug delivery. In:
Mathiowitz E, editor. Encyclopedia of controlled drug delivery. New York: Wiley
Interscience; 1999. vol 1. p. 342-7.
6. Peck GE, Baley GJ, Banker SG. Tablet formulation and design. In: Lieberman HA,
Lachman L, Schwartz JB editors. Pharmaceutical dosage forms: tablets. New York:
Marcel Dekker Inc; 2005. p. 131-245.
7. USP-NF 18. 23rd ed. Rockville: The United States Pharmacopoeial Convention Inc;
1996.
8. http://www.who.int/medicines/areas/quality_safety/quality_assurance/gmp/en/
index.html. [Access date: 2009 Nov 27].
9. http://www.fda.gov/ohrms/dockets/ac/00/slides/3657s2_01_hussain/ [Access date :
2009 Nov 27].
10. Banker GS, Anderson NR. Pharmaceutical dosage forms: tablets. In: Lieberman
HA, Lachman L, Kanig JL, editors. Volume 3. 2nd ed. New York: Marcel Dekker
Inc; 1990.
11. Stolar MW, Chilton RJ. Type 2 diabetes, cardiovascular risk, and the link to insulin
resistance. Clin Ther 2003;25 Suppl B:B4-31.
12. Hirose T, Miyashita Y, Takagi M, Sumitani S, Kouhara H, Kasayama S.
Characteristics of type 2 diabetic patients responding to voglibose administration as
an adjunct to sulfonylurea. Diabetes Res Clin Pract 2001 Oct;54(1):9-15.
13. Kageyama S, Nakamichi N, Sekino H, Nakano S. Comparison of the effects of
acarbose and voglibose in healthy subjects. Clin Ther 1997 Jul-Aug;19(4):720-9.
14. http://www.voglibose.com/ [Access date : 2009 Nov 27]
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15. http://www.drugbank.ca/drugs/DB04878 [Access date : 2009 Nov 27]
16. Matsui T, Shimada M, Saito N, Matsumo K. Alpha-glucosidase inhibition assay in
an enzyme-immobilized amino-micro-particulate. Anal Science 2009
Apr;25(4):559-62.
17. Woo JS, Ryu JK. Quantitative determination of pharmaceutical tablets using highperformance liquid chromatography-fluorescence detection with column
derivatization and mass spectrometric detection. J Pharm Biomed Anal 2006 Sep
26;42(3):328-33.
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9.
Signature of the Candidate
(K. NAVEEN)((Rajesh
10.
Remarks of the Guide:
Product development for generic marketing is a promising field. Formulation strategy for
new molecules must begin well in time to produce comparable product. The project is
specifically aimed at huge global market. Recommended for approval.
11.
Name & Designation (in BLOCK LETTERS)
11.1 Guide
Prof. Dr.R.S THAKUR
Professor and Head
Department of Pharmaceutics
Krupanidhi College of Pharmacy
Bangalore – 560035.
11.2 Signature of Guide
(Mrs. ROHINI R. M.)
K. SRINIVASU
Dy. Manager
Formulation and development,
BAL PHARMA LIMITED,
Bangalore-560 009.
11.3 Co-Guide
11.4 Signature of Co-Guide
11.5 Head of the Department
Prof. Dr.R.S THAKUR
Professor and Head
Department of Pharmaceutics
Krupanidhi College of Pharmacy
Bangalore – 560035.
11.6 Signature of HOD:
12.
12.1 Remarks of the Principal:
12.2 Signature of the Principal
Prof. Dr. AMIT KUMAR DAS
PRINCIPAL
Krupanidhi College of Pharmacy,
Chikka Bellandur,
Carmelaram Post,
Varthur Hobli,
Bangalore – 560035.
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