Useful in developing CR tablets

1. Development and evaluation of combined formulation for the immediate
delivery of vildagliptin and sustained delivery of metformin hcl with
comparison to the marketed formulation
CONTENTS:
 Aim and objective
 Introduction
 Plan of work
 Literature review
 Drug profile
 Experimental methodology

2. Aim
The aim of this study is to formulate and evaluate the bilayer tablet (immediate
delivery of vildagliptin and sustained release of metformin hcl with comparison to
marketed formulation
Objectives
• Preparation of immediate release layer of vildagliptin 400mg (polymers used
HPMC, PEO, Locust bean gum)
• Preparation of sustained release layer of metformin hcl 900mg (polymers used
HPMC, Eutragid, PEO)
• Preparation of bilayer tablet by direct compression method.
• Evaluation studies of bilayer tablet of vildagliptin and metformin hcl.
• Optimization by using DOE (to find the best levels for input factors)
• Comparative studies by using dissolution and disintegration time.

3. • Diabetes mellitus (DM) is a major public health issue affecting more than 400
million people worldwide.
• DM is caused either by deficiency of insulin secretion, damage of pancreatic β
cell or insulin resistance related to non-use of insulin.
• Type 1 DM and type 2 DM are the 2 types of DM.
• Type 1 DM is an autoimmune disorder that affects pancreatic cells which reduces
or impairs the production of insulin while type 2 DM is a result of impairment of
pancreatic beta cells that hinder the individual’s ability to use insulin
• The multilayered tablet concept has been long utilized to develop sustained
release formulations.
• Such a tablet has a fast releasing layer and may contain bi& or triple layers to
sustain the drug release.
• The pharmacokinetic advantage relies on the fact that drug release from
immediate release layer leads to a sudden rise in the blood concentration.
• However, the blood level is maintained at steady state as the drug is released
from the sustained release layer.
INTRODUCTION

4. Selection of drug-vildagliptin and metformin hcl
Selection of polymers and excipients
Method of preparation of bilayer tablet
Evaluation of bilayer tablet
Comparison with marketed bilayer tablets
PLAN OF WORK

5. DRUG FORMULATION METHOD PURPOSE REFERENCE
Vildagliptin
and metformin
HCL
Bilayer tablet Direct
compression
method
Treatment of
patient with
type II Diabetes.
Twinkle K.
Prajapati
(IJCAR) research
article
LITERATURE REVIEW

6. DRUG FORMULAT
ION
EXCIPIEN
T
METHOD PURPOSE REFERENC
E
Vildagliptin(
IR)and
metformin
hcl(SR)
Bilayer tablet IR-
Microcrystall
ine cellulose,
Magnesium
stearate,
Super
disintegrant,
SR-HPMC
K4M,
Carbopolol
934p,
Lactose
monohydrate
IR- Direct
compression
SR- wet
granulation
Treatment for
type II
diabetes
mellitus
Nishit Gohel,
Komal Patel,
Jignasa Modi,
Formulation
development
and evaluation
of modified
release tablet
using a fixed
dose
combination
of anti
diabetic drugs

7. Metformin
Summary: Metformin is a biguanide anti hyperglycemic used in conjunction with
diet and exercise for glycemic control in type 2 diabetes mellitus. It is also used off-
label for insulin resistance in polycystic ovary syndrome (PCOS).
Brand Names: Actoplus Met, Avandamet, Fortamet, Glucophage, Glucovance,
Glumetza, Glycon, Invokamet, Janumet, Jentadueto, Kazano, Kombiglyze,
Komboglyze, Qternmet, Riomet, Segluromet, Synjardy, Trijardy, Velmetia, Xigduo
Generic Name: Metformin
Structure:
BCS classification: class III
Weight: Average: 129.1636
Chemical Formula: C4H11N5
DRUG PROFILE

8. Synonyms: Dimethyl biguanid
Metformin combination products: DPP-4 inhibitors (sitagliptin,vildagliptin,
linagliptin, alogliptin, or saxagliptin), combination with SGLT2 inhibitors
(canagliflozin, empagliflozin, ertugliflozin, or dapagliflozin) or in combination
with pioglitazone.
Half-life: The plasma elimination half-life of metformin is 6.2 hours in the
plasma. The elimination half-life in the blood is approximately 17.6 hours
Clearance: Renal clearance is about 3.5 times greater than creatinine clearance,
which indicates that tubular secretion is the major route of metformin elimination.
Following oral administration, approximately 90% of the absorbed drug is
eliminated via the renal route within the first 24 hours
DOSE: 500mg – 1000mg

9. VILDAGLIPTIN
Summary: Vildagliptin is a once-daily dipeptidyl peptidase 4 (DPP-4) inhibitor used in
the management of type 2 diabetes mellitus.
Brand Names: Galvus, Jalra, Xiliarx
Weight Average: 303.3993
Structure:
Chemical Formula: C17H25N3O2
Half-life: The mean elimination half-life following intravenous administration is
approximately two hours. The elimination half-life after oral administration is
approximately three hours.
Clearance: After intravenous administration to healthy subjects, the total plasma and
renal clearance vildagliptin were 41 and 13 L/h, respectively
Dosage: 50mg or 100 mg

10. C:UsersLenovoNew folder16MAR2023VILDAGLIPTIN (DRUG).0 VILDAGLIPTIN (DRUG) SOLID 16-03-2023
3967.21
3926.34
3839.82
3817.27
3742.96
3675.15
3563.20
3411.59
2922.66
2851.28
1700.84
1654.52
1618.90
1541.37
1456.35
1402.91
1357.50
1250.59
500
1000
1500
2000
2500
3000
3500
Wavenumber cm-1
0
20
40
60
80
100
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11. Experimental methodology: SR-900MG
S.no Materials
1. Drug ( metformin)
2. HPMC
3. Eutragid
4. PEO
5. Magnesium stearate
6. Aerosil
7. MCC
5OO mg
300mg, 270mg, 225mg, 180mg
3mg
3mg
94mg, 124mg, 169mg, 214mg

12. S.NO MATERIALS
1 Drug (vildagliptin)
2 HPMC
3 HPMC+PEO
4 Locust bean gum + PEO
5 HPMC+ Locust bean gum
6 Mg stearate
7 Aerosil
8 MCC
Immediate Release: 400mg
100mg
100mg
75mg+ 75mg
75mg+75mg
75mg+ 75mg
2mg
2mg
196mg, 146mg

13. SR- drug (metformin is added to the polymers (hpmc, eutragid and PEO)
coshift and mix well
magnesium stearate ,aerosil and mcc is added.
pass through 60 mesh
Double compression
( tablet compression machine)
Preparation of SR layer (metformin) and IR vildagliptin {double compression)
Direct compression method
IR- drug (vildagliptin) + hpmc, PEO, locust bean gum, mg stearate, aerosil, mcc

14. • Hardness
• Angle of repose
• Disintegration
• Dissolution
• Friability
• Weight variation
• Bulk density
Evaluation