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PRESENTED BY

M.KINNERA (153H1R0046)
M.JANAKI RAM (153H1R0047)
M.RATNA BHAVANI (153H1R0048)

M.V.S.MANVITHA (153H1R0049)

N.SAI MONOHAR (153H1R0050)

N.LALITHAA SRI (153H1R0051)

UNDER THE SUPERVISION OF


CH.SIVA RAMESH M.Pharm.
Asso.professor
ACOP
Aim and objectives
Introduction
Selection of drug
Drug profile
Polymers used
Literature review
Method of preparation
Evaluation of Solid Dispersions
Results and discussion
Conclusion
References
To Design And Carry Out In Vitro Evaluation Solid
Dispersions Of Glimepiride For Dissolution Rate
Enhancement by using different hydrophilic polymers.
OBJECTIVES
 To formulate solid dispersions of Glimepiride using
hydrophilic carriers in different concentrations and to
determine their effect on solubility of drug.
To prepare solid dispersions by fusion method
To characterize & evaluate the prepared solid dispersions.
To carry out the in-vitro dissolution studies of prepared
solid dispersions.
The solid dispersion approach has been widely and
successfully applied to improve the solubility, dissolution
rate and consequently the bioavailability of poorly water
soluble drugs.
Solid dispersions (SDs) are defined as the dispersion of one
or more active ingredients in an inert hydrophilic carrier or
matrix in a solid state.
SOLID DISPERSION – METHODS OF PREPARATION
•Melting method Solvent evaporation method
• Melting solvent method Melt extrusion methods
• Lyophilization techniques Melt agglomeration Process
• The use of surfactant Electrospinning
Glimepiride has been selected as the test drug.
 Glimepiride is a BCS Class II drug having low aqueous
solubility and high membrane permeability
 Bioavilability of the drug is low (25%) due to poor
aqueous solubility.
Low water soluble drugs often exhibit low dissolution
profile and oral bioavailability problems . Therefore, the
objective of the present study was to improve in vitro
dissolution profile, there by bioavailability of Glimepiride
using solid dispersions by fusion method
 Glimepiride solid dispersions were prepared to enhance
solubility of drug and there by enhancing bioavailability.
DRUG PROFILE
Name : Glimepiride
Description : Glimepiride is the first III
generation sulphonyl urea it is a very potent sulphonyl urea
with long duration of action.
Solubility: It is insoluble in water, freely soluble in alcohol
Half life :4-5 hrs
Use: treatment of type II diabetes mellitus.
IUPAC Name: 3-ethyl-4-methyl-N-{2-[4-({[(4-
methylcyclohexyl)carbamoyl]amino}sulfonyl)phenyl]ethyl}-
2-oxo-2,5-dihydro-1H-pyrrole-1-carboxamide
Chemical Formula: C24H34N4O5S
MOA:Glimepiride likely binds to ATP-sensitive potassium
channel receptors on the pancreatic cell surface
POLYMERS USED:
Urea
PEG-4000
PLAN OF WORK
Preparation of Glimepiride standard graph.
Evaluation of drug excipient interaction by FTIR.
Preparation of solid dispersion of Glimepiride using PEG-
4000, Urea.
 Evaluation of solid dispersion:
a) Drug content,
b)Dissolution studies.
c)Flow properties
 Chitra K et al.27studied the influence of solubility of Rofecoxib
released from the solid dispersion system using different water-soluble
carriers like Urea, Mannitol, PEG 6000, and PVP by common solvent
method and melting method.
 Gupta MK et al.28 reported the mechanism for further enhancement
in drug dissolution from solid dispersion granules upon storage.
Naproxen and a non-proton donating drugs were studied; Granules
containing progesterone (a non-proton donating drug) do not show an
increase in the amount of drug hydrogen bonded to Neusilin upon
storage.
 Vippagunta SR et al.29 conclude the method of preparation of solid-
state characterization of Nifedepine solid dispersion. The results
indicate that the Nifedepine solid dispersion is physically stable over 8
weeks. Also indicate that Nifedepine is released faster from the solid
dispersion than from the pure crystalline drug of the same particle
size.
 Lifa H U et al.30studied the dissolution improvement of poorly soluble
SILY from solid dispersion of PEG 6000 can be illuminated by the
changes of the lattice parameters of PEG 6000 on drug
CALIBRATION CURVE
buffer: 6.8pH phosphate buffer
Lambda max:232nm
S.no Concentr Absorban
ation ce
1 0ug/ml 0
2 5ug/ml 0.071
3 10ug/ml 0.134
4 15ug/ml 0.201
5 20ug/ml 0.261
6 25ug/ml 0.322
7 30ug/ml 0.382
8 35ug/ml 0.443
Fig:1 calibration
curve
Fusion Method

Urea and PEG 4000 in proportions viz. 1:1, 1:2, 1:3, 1:4
(Drug: Carrier)

Melted in a porcelain dish at 80-85ºC and to this


calculated amount of glimepiride was added
with thorough mixing for 1-2 minutes followed
by quick cooling.

The dried mass was then pulverized by passing


through sieve no.85 and stored in a dessicator
until used for further studies
Drug :
SNO Formulation Composition
Polymer
Solid dispersion urea formulation- 1:1
1 1 Glimepiride +Urea

Solid dispersion urea formulation- 1:2


2 2 Glimepiride +Urea

Solid dispersion urea formulation- 1:3


3 3 Glimepiride Urea

Solid dispersion urea formulation- 1:4


4 4 Glimepiride +Urea

Solid dispersion PEG formulation-1 1:1


5 Glimepiride +PEG 4000

Solid dispersion PEG formulation- 1:2


6 2 Glimepiride +PEG 4000

Solid dispersion PEG formulation- 1:3


7 3 Glimepiride +PEG 4000

Solid dispersion PEG formulation- 1:4


8 4 Glimepiride +PEG 4000
1 • Solubility studies

• Flow properties
2

• Drug content
3

• Drug release studies


4
Pure drug

Pure drug + polymers


drug with polymers showed no significant variation in height, intensity and position of
peaks, suggesting that
drug and excipients were compatible. There is no interaction between drug and polymer.
solubility studies were conducted in order to find out the
solubility of the solid dispersions in water, by dissolving
solid dispersions equivalent to 100 mg of the drug in 100 ml
of distilled water. This solution was sonicated for 1hr and
filtered through Whatmann filter paper 44.The filtered
solution was analyzed for drug release from the solid
dispersion by Uv-Visible spectrophotometer at 232 nm.
sample Carrier Solution Solubility mcg/ml
PURE DRUG Pure drug in water 19.3
Solid dispersion urea Glimepiride +Urea(1:1) 24.57
formulation-1
Solid dispersion urea Glimepiride + Urea (1:2) 26.41
formulation-2
Solid dispersion urea Glimepiride + Urea (1:3) 29.53
formulation-3
Solid dispersion urea Glimepiride + Urea (1:4) 35.51
formulation-4
Solid dispersion PEG 4000 Glimepiride +PEG(1:1) 25.1
formulation-1
Solid dispersion PEG 4000 Glimepiride + PEG( (1:2) 29.5
formulation-2
Solid dispersion PEG 4000 Glimepiride + PEG( (1:3) 33.3
formulation-3
Solid dispersion PEG 4000 Glimepiride + PEG( (1:4) 45.56
formulation-4
FLOW PROPERTIES
 CARR’S INDEX:-it is an indication of compressibility
 Of powder.it is calculated by formula:-
C=TD-BD/TD×100
Carr’s index value of 15 indicates good flowability.
 Hausner’s Ratio:-a hausners ratio greater than 1.25 is
indicative of poor flowability.it is calculated by:-
H=TD/BD
ANGLE OF REPOSE:-is the angle of the conical pile
produced when a granular material is poured on
horizontal plane.it is calculated by:-
ѳ=tan⁻¹h/r TD=tapped density
BD=bulk density
h=Height
Sample Carr’s index Hausner’s Angle of
ratio repose(°)
38.37 1.62 45
PURE DRUG
Solid drug dispersion urea 16.77 1.201 30.32
formulation 1
Solid drug dispersion urea 16.62 1.199 29.72
formulation 2
Solid drug dispersion urea 16.52 1.197 29.51
formulation 3
Solid drug dispersion urea 16.19 1.193 29.68
formulation 4
Solid drug dispersion PEG4000 14.33 1.167 29.24
formulation 1
Solid drug dispersion PEG4000 13.98 1.162 28.59
formulation 2
Solid drug dispersion PEG4000 15.22 1.179 30.03
formulation 3
DRUG CONTENT
 The drug content was determined by accurately weighing
out solid dispersion equivalent to 100 mg of Glimepiride in
a 100 ml volumetric flask. Approximately 20 ml of
Methanol was added and sonicated for 30 minutes. The
volume was made up to 100 ml with buffer and filtered. An
aliquote 10 ml the drug solution was transferred to a 100
ml volumetric flask and volume was made upto 100ml with
buffer. An aliquote 1 ml the drug solution was transferred
to a 10 ml volumetric flask and volume was made upto
100ml with buffer. The absorbance was measured at 232
nm and the value was compared with that of a standard 10
µg/ml solution.

Assay=test abs/std abs×dilution factr×1/wt sample


Drug:
S.no Formulat (%) Drug
carrier content

1 PD 100
SDUF1
2 1:1 96.4
SDUF2
3 1:2 97.6 PD-PURE DRUG

SDUF3 SDUF-SOLID DISPERSION


4 1:3 95.8 UREA FORMULATION

SDUF4 SDPF-SOLID DISPERSION


5 1:4 99.49 PEG FORMULATION

SDPF1
6 1:1 98.8
SDPF2
7 1:2 97.8
SDPF3
8 1:3 99.5
SDPF4
9 1:4 97.4
USP type I Dissolution Testing Apparatus (LABINDIA )
 Dissolution medium - phosphate buffer pH 6.8
Volume – 900ml
 RPM – 50 , Temperature - 37 ̊C±0.5 ̊C
Sampling intervels-5,10,15,20,30,45,60,90 mins
Sample volume:5ml withdrawn at fixed time intervals &
replaced with 5ml of pH 6.8 phosphate buffer.
analyzed spectrophotometrically at 232nm
Time SDUF1 SDUF2 SDUF3 SDUF4 SDPF1 SDPF2 SDPF3 SDPF4
PD
(min)

5 9.7 18 22 30 32 17 20 19 29

10 18.6 29 35 42 46 28 31 30 37

15 24.8 36 44 56 54 36 37 39 46

20 28.1 49 53 68 69 44 45 47 55

30 30.3 63 67 82 80 57 59 65 68

45 35.5 75 80 89 97 63 66 72 80

60 37.3 87 89 94 97 72 79 85 99

90 42.2 88 91 93 96

PD-pure drug
SDUF-solid dispersion urea formulation
SDPF-solid dispersion PEG formulation
Fig:- 1 Comparison of Dissolution Profiles of
SolidDispersions of UREA and Pure Drug

Fig:- 2 Comparison of Dissolution Profiles of SolidDispersions of PEG


and Pure Drug
COMPARITIVE STUDIES OF UREA&PEG
UREA PEG

Prepared mixtures: - 1:1,1:2,1:3,1:4 Prepared mixtures: - 1:1,1:2,1:3,1:4

Maximum Solubility : - 35.5 mcg/ml Maximum solubility: -45.5 mcg/ml

Maximum solubility exhibiting ratio :-1:4 Maximum solubility exhibiting ratio : 1:4
But more than urea.
Drug release kinetics:- zero order Drug release kinetics:- zero order

Drug release :- 97% in 60mins Drug release: - 99% in 60mins


CONCLUSION:
From the results of the present study it can
be concluded that the solubility of the drug can
be significantly enhanced with the polymers
used. With increase in the carrier content there
is increase in the solubility resulting in
enhanced dissolution rate.

Formulation containing 1:4 ratio of drug:


PEG4000 is considered as best formulation
as it has shown highest drug release in short
time i.e. 99% in 60 min. Therefore PEG 4000
can be successfully employed for developing
solid dispersions of poorly soluble drugs like
Glimperide
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