Rohit Gurav presented on Supersaturated Drug Delivery Systems (S-SNEDDS) to improve the bioavailability of poorly water soluble drugs. S-SNEDDS generate and maintain drug concentrations above equilibrium solubility for higher absorption. They use precipitation inhibitors to prevent crystalline drug precipitation in the GI tract. Rohit discussed preparing a solid S-SNEDDS of glipizide using HPMC-E5 as a precipitation inhibitor. In vitro and in vivo tests showed the solid S-SNEDDS improved glipizide's dissolution, absorption, and hypoglycemic effects compared to the pure drug and commercial product. S-SNEDDS are a promising approach for oral delivery of class II-IV

1. “Supersaturated Drug Delivey System
:S-SNEDDS”
• Presented By :
Mr. ROHIT GURAV
M. Pharm (2nd Sem.)
Roll no. 510
• Guided By:
Prof. V. M. GAMBHIRE
M. Pharm
Department of Pharmaceutics

2. Solubility
Absorption
*Rohit Gurav 204-04-2017
Introduction
Bioavailability
40% NCEs
> one-third

3. Supersaturating DDS
Drug Concentration
exceeds the
equilibrium
solubility
Higher Bioavailability
04-04-2017 *Rohit Gurav 3

4. DDS based on
Supersaturation
Non Inclusion
Complex
Supersaturated
Liposomes
Novel Drug
Carrier
Material
Nanodrug
Solid
Dispersion
Supersaturated
SEDDS
Drug Delivery System based on
Supersaturation
04-04-2017 *Rohit Gurav 4
*Yang M. et. al, Bioavailability Improvement Strategies for Poorly Water-Soluble Drugs Based on the Supersaturation
Mechanism: An Update, J Pharm Pharm Sci 19(2) 208 - 225, 2016.

5. SNEDDS
Oil
Drug
Super
SNEDDSSNEDDS
PPI
Bioavailability HighLow
Supersaturated SNEDDs
04-04-2017 *Rohit Gurav 5

6. Spring and Parachute Approach
6
Generation of the supersaturated state by high loading dose (Spring)
Maintenance of the supersaturated state by means of precipitation
inhibitors (Parachute)
04-04-2017 *Rohit Gurav
*Yang M. et. al, Bioavailability Improvement Strategies for Poorly Water-Soluble Drugs Based on the Supersaturation
Mechanism: An Update, J Pharm Pharm Sci 19(2) 208 - 225, 2016.

7. Supersaturated SNEDDS are thermodynamically stable
SNEDDS containing precipitation inhibitors
 Poly vinyl Pyrrolidone (PVP)
 Hydroxy Propyl Methyl Cellulose
 Hydroxy propyl cellulose (HPC)
 cellulose acetate phthalate(CAP)
7
Precipitation
inhibitors
Adsorption
on crystal
surface
Inhibition of
nucleation &
crystal
growth
Maintainance of
supersaturated
state
Mechanism of precipitation inhibition
aADSORPTION
aMOBILITY
04-04-2017 *Rohit Gurav
Brouwers J., Supersaturating Drug Delivery Systems: The Answer to Solubility-Limited Oral Bioavailability,
Journal Of Pharmaceutical Sciences, Wiley InterScience, Vol. 98, No. 8, August 2009.

8. SNEDDS Supersaturated SNEDDS
Precipitation of crystalline drug in GIT Retard the precipitation of crystalline
drugs on GIT due to precipitation
inhibitors
Low loading dose (50-90% of
equilibrium solubility of drugs)
High loading dose (150-200% of
equilibrium solubility of drugs)
Lesser bioavailability More bioavailability
Lesser half life More half life
High amount of surfactant is required Low amount of surfactant,
less toxicity
Difference between SNEDDS and
Supersaturated SNEDDS
804-04-2017 *Rohit Gurav

9. Not suitable for CR drug applications
Compatibility of nanoemulsion
component with capsule
Improving oral bioavailability
Reduction in the drug dose
Long term colloidal stability
Ease of manufacture & scale up
Reduction in intra and inter subject variability
 Advantages Disadvantages
04-04-2017 *Rohit Gurav 9

10. COMPONENTS OF SUPERSATURATED
SNEDDS
10
Super
SNEDDS
Oil
phase
Surfactant
Cosurfactant
PPI
Mono and di
glycerides,
Isopropyl
myristate,
Soybean oil,
Glyceryl
monooleate,
• Span®
• Tween®
• Cremophor
e®
• Plurol®
• Labrafil®
• PG
• PEG
• Glycol
ethers
• HPMC
• PVP
04-04-2017 *Rohit Gurav
*Brouwers J., Supersaturating Drug Delivery Systems: The Answer to Solubility-Limited Oral Bioavailability, Journal
Of Pharmaceutical Sciences, Wiley InterScience, Vol. 98, No. 8, August 2009.

11. Mechanism of Self
Emulsification
11
Increasing the entropy of dispersion system
Reduction in free energy (ΔG) of formation
Spontaneous emulsification
Surfactant + oil phase
Form monolayer on oil droplets
Reduces interfacial tension between droplets
04-04-2017 *Rohit Gurav

12. Methods For Preparation of
Supersaturated SNEDDS
12
High Pressure Homogenization
Micro Fluidization
Sonication
04-04-2017 *Rohit Gurav
SagarK. Savale, A Review - Self Nanoemulsifying Drug Delivery System (SNEDDS), International Journal of
Research in Pharmaceutical and Nano Sciences. 4(6), 2015, 385 - 397.

13. 13
High Pressure Homogenization
Coarse Dispersion
Co-
surfactant
Oil Surfactant
High pressure homogenization at
500 -5000 psi
Fine droplet of dispersion
Supersaturated SNEDDS
Excess loading dose
of drug + PIs
04-04-2017 *Rohit Gurav

14. 14
Oil phase
Heat at 40°-
45°c for 30 sec
SNEDDS
SUPER
SNEDDS
Heating &
cooling method
Co-surfactant Exceed dose of
Drug + PI
Surfactant
Sonication Method
Sonication
04-04-2017 *Rohit Gurav

15. *Rohit Gurav 1504-04-2017
Micro fluidization

16. 04-04-2017 16*Rohit Gurav
• Emulsification time
• Droplet size, zeta potential
• In-vitro dissolution study
• In-vivo Study
• Stability studies

17. 17
04-04-2017
*Rohit Gurav
Objective: To prepare a solid S-SNEDDS to improve dissolution, absorption, pharmacodynamic
effects of a poorly water-soluble drug Glipizide.
Case Study

18. *Rohit Gurav 1804-04-2017
PPI HPMC-E5 (0.5, 1, 3, 5, 7.5, 10% w/w)
mixtures were mixed for 5 min using a Cyclo-mixer
liquid SNEDDS (10 gm) (Glipizide + SNEDDS
preconcentrate)
Liquid S-SNEDDS
Method

19. *Rohit Gurav 1904-04-2017
liquid S-SNEDDS (10gm) + Calcium carbonate (15 g)
Talc (2 gm) was added to the above mass
Passed through a mesh (250-mm)
Solid S-SNEDDS

20. Analytical Methodology
*Rohit Gurav 2004-04-2017
Sr. No Parameters Specifications
1 Column used
Luna C8100* 4.6mm, 3μm
Phenomenex C18
2 Absorbance detector (λ) 226 nm
3
Isocratic elution
(Mobile phase)
Acetonitrile: Potassium
dihydrogen phosphate
35:65 (V/V)
4 pH 4.5
5 Injection Volume 20μL
6 Flow rate 0.8 ml/min

21. 21
Results
and
Discussion

22. 22
04-04-2017
*Rohit Gurav
SEM images of a, glipizide; b, solid S-SNEDDS; c, solid S-SNEDDS blank; d, physical mixture.
Scanning Electron Microscopy

23. In-vitro Supersaturation
test
*Rohit Gurav 2304-04-2017
Apparent glipizide concentration-time profile obtained from different concentration of HPMC-E5
during in-vitro supersaturation test

24. 24
04-04-2017
*Rohit Gurav
In-vitro release profiles for the solid S-SNEDDS, solid SNEDDS, Glucotrol®, and glipizide (pure drug).
In-Vitro Release

25. *Rohit Gurav 2504-04-2017
Plasma concentration-time profile of glipizide in fasted rabbits after oral administration of glipizide, Glucotrol®,
solid SNEDDS and solid S-SNEDDS
In-Vivo Release

26. 26
04-04-2017
*Rohit Gurav
Observed and predicted pharmacokinetic parameters for glipizide after oral administration of pure drug,
Glucotrol®, solid-SNEDDS and solid S-SNEDDS to rabbits (n = 6).
In-Vivo Release

27. 2704-04-2017 *Rohit Gurav
The mean percentage decrease in plasma glucose in normal rabbit after oral administration of glipizide,
Glucotrol®, solid SNEDDS and solid S-SNEDDS.
Pharmacodynamic Study

28. • Solid S-SNEDDS resulted in a large surface area for
enhanced drug solubilisation and dissolution.
• The incorporation of HPMC-E5 into solid S-SNEDDS
effectively inhibited drug precipitation
• This stable solid supersaturatable formulation
substantially improved in-vitro release, in-vivo
absorption, thus may offer a useful oral dosage form
option for oral delivery of glipizide.
28
04-04-2017
*Rohit Gurav
Conclusion :Case Study

29. 04-04-2017 29*Rohit Gurav
• Supersaturated SNEDDS is promising approach for
poorly soluble drug candidates of class II, III and IV
• Supersaturated SNEDDS formulation with optimum
droplet size and zeta potential gives better oral absorption
• Cost effectiveness, ease of manufacture and scale up
CONCLUSION

30. References
• Yang M. et. al, Bioavailability Improvement Strategies for Poorly Water-
Soluble Drugs Based on the Supersaturation Mechanism: An Update, J Pharm
Pharm Sci 19(2) 208 - 225, 2016.
• Brouwers J., Supersaturating Drug Delivery Systems: The Answer to
Solubility-Limited Oral Bioavailability, Journal Of Pharmaceutical Sciences,
Wiley InterScience, Vol. 98, No. 8, August 2009.
• Dash R. N. et. al, Solid supersaturatable self nanoemulsifying drug delivery
systems for improved dissolution, absorption and pharmacodynamic effects of
Glipizide, Journal of Drug Delivery Science and Technology, Elsevier, 28
(2015) 28-36.
• SagarK. Savale, A Review - Self Nanoemulsifying Drug Delivery System
(SNEDDS), International Journal of Research in Pharmaceutical and Nano
Sciences. 4(6), 2015, 385 - 397.
*Rohit Gurav 3004-04-2017

31. • Sweta Modi, Enhanced active liposomal loading of a poorly soluble
ionizable drug using supersaturated drug solutions, Journal of Controlled
Release, Elsevier, 162 (2012) 330–339
*Rohit Gurav 3104-04-2017

32. 3204-04-2017