Plotting of ternery phase diagram for preparation of SMEDDS

M.VAMSHIKRISHNA
M.PHARMACY 1ST YEAR 1ST SEMESTER
HT.NO: 19004P-1303
DEPARTMENT OF INDUSTRIAL PHARMACY
UCPSC,KAKATIYA UNIVERSITY.
1

CONTENTS
2
 INTRODUCTION
 DEFINITION
 ADVANTAGES AND DISADVANTAGES
 FACTORS AFFECTING SMEDDS
 FORMULATION OF SMEDDS
 EVALUATION TESTS
 CONCLUSION
 REFERENCES.

INTRODUCTION OF SMEDDS
In drug discovery,about 40% of new drug cadidates displays
low solubility in water, which leads to poor bioavailability.
Lipid based delivery system are suitable for this kind of
problem by one of the most popular approach is “self micro
emulsifying drug delivery system (SMEDDS)”.
These are shown to be reasonably successful in improving the
oral bioavailability of poorly water soluble and lipophillic drugs.
The improvement of oral bioavailability is mainly by two
mechanisms i.e 1.electrostatic
2.mucoadhesive 3

 DEFINITION :
SMEDDS are Isotropic mixtrure of drug, oil/lipid,
Surfactactant, Co-surfactant, which form a fine
emulsion /lipid droplets ranging approximately
<250nm in size on dilution with physiological fluid.
4

ADVANTAGES AND DISADVANTAGES
ADVANTAGES DISADVANTAGES
 oral bioavailability improvement.  Increase in side effects.
 Ease of manufacture and scaleup.  Precipitation of the lipophillic
drugs.
 Prolonged release of medicament.  Chemical instabilities.
 Useful in both solid and liquid
dosage forms.
 Irritates GIT.
5

FACTORS AFFECTING SMEDDS
 Drug dose
Solubility of drug
Droplet size and charge
6

FORMULATION OF SMEDDS
1) Composition
A) Active pharmaceutical ingredient(API)
B) Oils
C) Surfactant
D) Co-surfactant or Co-solvent
7

A) Active pharmaceutical ingredient (API)
 It should be soluble in oil phase as this influence the
ability of SMEDDS to maintain the API solubilised
form.
B) Oil
 It solubilises the lipophillic drug in a required
quantity or facilitate self emulsification and also
enhances the absorption through the GIT.
Eg: corn oil, olive oil, soyabean oil.
8

C) Surfactant
 The most widely recommended one being the Non-
Ionic surfactants with a relatively high hydrophillic-
lipophillic balance(HLB) values are used in
formulation of SMEDDS.
 The usual surfactant strength ranges having 30-60%
W/W in order to form stable SMEDDS.
Eg: sorbitan esters(spans)
polysorbates(Tween80).
9

D) Co-surfactant or Co-solvent
 Hydrophillic co-surfactants are preferabley alcohol
of intermediate chain length wich reduce the O/W
interface and allows the spontaneous formation of
microemulsion.
 Organic solvents are enable the dissolution of large
quantities of either the hydrophillic surfactant or
the drug in the lipid base.
Eg:Ethanol,propyleneglycol(PG),polyethyleneglycol.
10

2) Construction of ternery phase diagram
o The following methods are used to plot ternery phase
diagram for SMEDDS.
A) Phase titration method.
B) Phase inversion method.
A) Phase titration method :
The pseudo-ternery phase diagrams is constructed by
titration of homogeneous liquid mixture of oil,
surfactant, and co-surfactant with water. 11

 Surfactant and Co-surfactant is mixed (Smix) in
different volume ratios (1:1),(2:1),(3:1),(4:1).
For each phase diagram Oil and specific surfactant /
Co-surfactant (Smix) ratio is mixed thoroughly in
different volume ratios from 1:9 to 9:1 (1:9, 2:8, 3:7,
4:6, 5:5, 6:4, 7:3, 8:2, 9:1) in different glass vials.
 Each mixture is then slowly titrated with water untill
they showed turbidity.
12

Identify the regions of phase diagrams based on the
results, appropriate percentage of oil,surfactant, and
co-surfactant is selected,correlated in the phase
diagram.
13

B) Phase inversion method :
 Phase inversion of microemulsion occur upon
addition of excess of dispersed phase or in resopnse
to temperature.
 During phase inversion drastic physical changes
occur including changes in particle size that can be
affect drug release both in vitro and in vivo.
 For non-ionic surfactant, this can be achieved by
changing the temperature of the system.
15

o Forcing a transition from an o/w microemulsion at low
temperature to a w/o microemulsion at higher temperature
16

EVALUATION TESTS
1) Droplet size and Particle size measurement
2) Refractive index and Percent transmission
3) Zeta potential measurement
4) Thermodynamic stability studies
5) In vitro and In vivo studies
6) Bioavailability study
7) Dispersibility test 17

1) Droplet size and particle size measurement:
 The droplet size analysis of microemulsion is
performed by Transmission electron microscopy
(TEM).
 The optimal droplet size is in range of 100 -500nm.
 The particle size of microemulsion is determined by
Photon correlation sprectoscopy (PCS) or Scanning
electron microscopy (SEM) which can measure sizes
between 10 and 5000nm.
18

2) Refractive index and percent transmission:
This test proves the clearance of formulation.
The refractive index of SMEDDS is measured by
refractometer and compared with that of water.
The percent transmission of the system is measured
at perticular wavelength using UV-visible
sprectophotometer keeping distilled water as blank.
Eg: If refractive index is similar to refractive index of
water (1.333) and percent transmittance above 90%,
then formulation have a transparent nature. 19

3)Zeta potential measurement:
20
It is generally measured by
zeta potential analyser or
zetameter system to
identify the charge of
droplets.
 The SMEDDS fomulation
with zeta potential greater
than ±30mv are
charecterised as stable.

4)Thermodynamic stability studies:
 SMEDDS is diluted with distilled water and to check
the stability by keep at two different temperature
ranges and [2-8°c(refregerator) and room
temperature] and observed for phase separation.
 The optimised formulation is exposed to three freeze
thaw cycles between -21°c and +25°c with storage at
each temperature for not <48hrs to check
thermodynamic stability of emulsion.
21

5) In-vitro and In-vivo studies:
 In-vitro drug release of microemulsion is
determined by dialysis bag method.
 The sample is analysed in perticular λmax of drug
molecle by using sprectophotometer.
 In-vivo study conducted in male albino rats having
200-250gm of weight. (n=6)
 Perform the statistical analysis of collected data.
22

6) Bioavailability study:
 Based on the self emulsification properties,
particle size data and stability of microemulsion,
the formulation is selected for bioavailability.
 calculate the pharmacokinetic parameters of
maximum plasma concentration(Cmax),
corresponding time (tmax) for oral
administration.
23

7)Dispersibility test:
 Dispersibility test can be done by using USP XXII
dissolution apparatus 2.
 The In-vitro performance of the formulation is
visually determined by using grading system.
Grade-A: Rapidly forming(within 1minute),having
clear and bluish appearance.
Grade-B: Rapidly forming, slightly less clear, having
bluish white appearance. 24

Grade-C: Fine milky emulsion that forms within
2minutes
Grade-D: Dull grayish white emulsion having slitely oil
appearance that slow to emulsify.
Grade-E: Formation of poor emulsification with large oil
soluble present on the surface.
25

 CONCLUSION
 It is a novel approach for the formulation of drug
compounds with poor aqueous solubility.
 The oral delivery of hydrophobic drugs can be made
possible by SMEDDS, it is shown to improve oral
bioavailibility.
 By this approach ,it is possible to prolong the release of
drug via incorporation of poymer in composition.
 In future, SMEDDS will continue to advance and will
represent a viable alternative to incease oral use of
various poorly water soluble drugs. 26

References:
27
 Vikas sharma.et.al,(2012),SMEDDS: A NOVEL APPROACH FOR LIPOPHILIC
DRUGS,INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCENS AND
RESEARCH,Vol(3),page.no(2441-2450).
 Anand.kyatanwar.et.al,(2009),Self Micro-Emulsifying Drug Delivery
System(SMEDDS),Review Article,vol(3),page no(75-83).
 Priyanka kalamkar.et.al,(2016), A Review on “Self Micro Emulsifying Drug
Delivery System (SMEDDS)”,INTERNATIONAL JOURNAL OF PHARMACY
&PHARMACEUTICAL RESEARCH,Vol(6),page no(361-373).
 Katla Venu Madhv.et.al,(2017),Self Micro Emulsifying particles of loratadine
for improved oral bioavailability:preparation,
Charecterization and In vivo evaluation,Journal of pharmaceutical
investigation.

Plotting of ternery phase diagram for preparation of SMEDDS

More Related Content

What's hot (20)

Similar to Plotting of ternery phase diagram for preparation of SMEDDS (20)

Recently uploaded (20)

Plotting of ternery phase diagram for preparation of SMEDDS