SNEDDS definition and the advantages of it, The detailed Formulation of SNEDDS

1. SELF-NANO
EMULSIFYING DRUG
DELIVERY SYSTEMS
PRESENTED BY- RAJDEEPA KUNDU (JISU/2022/0198)
Under the guidance of – Dr Tapan Kumar Shaw (Associate
professor of JIS university)

2. INTRODUCTION
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Self-nano emulsifying drug delivery systems
(SNEDDS) are anhydrous homogenous liquid
mixtures consisting of oil, surfactant, drug and
co-Surfactant or solubilizer, which spontaneously
form oil-in-water nano-emulsion of approximately 200
nm or less in size upon dilution with water under
gentle stirring.
It shows good bioavailability of the highly lipophilic,
poorly water-soluble drug by various mechanisms
but also it can improve oral bioavailability of
hydrophobic drugs by several mechanisms.

3. FORMULATION
1. Oil Phase:
• The oil phase has great importance in the formulation of SNEDDS as physicochemical properties
of the oil (e.g., molecular volume, polarity and viscosity) significantly govern the spontaneity of
the nano-emulsification process, the droplet size of the nano-emulsion, drug solubility
and biological fate of nano-emulsions and drug.
• Usually, the oil, which has maximum solubilizing potential for the selected drug candidate, is
selected as an oily phase for the formulation of SNEDDS. This helps to achieve the maximal
drug loading in the SNEDDS
• the choice of the oily phase is often a compromise between its ability to solubilize the drug and its
ability to facilitate the formation of nano-emulsion with desired characteristics. ex-medium-chain
monoglycerides and fatty acid esters (e.g., ethyl oleate), are easy to nano-emulsify compared
with long-chain triglycerides(fixed oil) but long-chain triglycerides have demonstrated a great
ability to improve intestinal lymphatic transport of drugs (responsible for preventing first-pass
metabolism of drugs) compared with medium-chain triglycerides. In certain cases, using a
mixture of oils can also be used to meet the optimum properties of the oily phase.

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2. Surfactant:
• The concentration of the surfactant in the SNEDDS has considerable influence on the droplet size
of nano-emulsions.
• The acceptability of the selected surfactant for the desired route of administration and its regulatory
status (e.g., generally regarded as safe [GRAS] status) must also be considered during surfactant
selection.
• Cuine and coworkers have demonstrated that the surfactant structure and concentration can
influence the drug precipitation in the GI tract, which in turn influences the bioavailability of
the drug.
• Certain surfactants might cause irritation to the GI mucosa and skin at higher concentrations.
• The surfactants are not innocuous and they have favourable and/or unfavourable biological effects
depending upon the chemical nature and the concentration of the surfactant. The unfavourable
characteristics associated with the surfactant might diminish after association with the oily phase.
• Example of surfactant- Polysorbates(Tween 80, Tween20), Sorbitan esters (Span20, Span60,
Span80), POE-stearate

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3. Co-emulsifiers, cosurfactants or solubilizers:
• Coemulsifiers, cosurfactants or solubilizers are typically employed in the SNEDDS for
pharmaceutical use. They can be incorporated in SNEDDS for different purposes, including:
 increase the drug loading to SNEDDS;
 modulate the self-nano emulsification time of the SNEDDS;
 modulate droplet size of nanoemulsion.
• The incorporation of the co-emulsifiers or solubilizers in SNEDDS may result in an expanding
self-nano emulsification region in the phase diagrams.
• are often used in the SNEDDS to improve drug loading and time required for self-nano
emulsification.In certain cases, short-chain alcohols, such as ethanol, have also been used by
investigators.
• Examples- Polyethylene glycols (PEG 400), Alkane diols and triols (Propylene glycol, Glycerol)

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5. Drug:
• It is important to know that the therapeutic agent of
interest can also havea significant impact on the
various aspects of SNEDDS.
• phase behavior and nanoemulsion droplet size.
Various physicochemical properties of the drug,
such as log P, pKa, molecular structure and
weight, presence of ionizable groups and also the
quantity have considerable effects on the
performance of SNEDDS.
• ncorporation of a drug into SNEDDS can lead to
an increase in the nanoemulsion droplet size
compared with SNEDDS without the drug.
• The amount of drug incorporated in SNEDDS also
has an influence on its properties. The droplet size
of the nanoemulsion rises with increases in the
amount of the drug.
4.Aquous Phase:
• The droplet size and stability of nanoemulsion is
influenced by the nature of aqueous phase where
SNEDDS would be introduced. Hence, pH and ionic
content of aqueous phase should be given due
importance while designing SNEDDS.
• The pH of the aqueous phase can have a dramatic
influence on the phase behavior of the SNEDDS,
especially when a drug with pH-dependent solubility is
loaded in the system
• It is well known that electrolytes can have influence on
the nanoemulsion characteristics, such as droplet size
and physical stability.
• Hence, it is advisable to evaluate the self-nano
emulsification of the SNEDDS and the characteristics
of the resultant nanoemulsion in aqueous phases with
varying pH and/or electrolyte concentration (depending
upon the type of application).

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8. FACTORS LIMITING ORAL BIOAVAILABILITY OF
DRUGS & POTENTIAL OF SNEDDS IN ORAL DRUG
DELIVERY
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 Dissolution rate-limited absorption- These therapeutic agents belong to BCS class II and IV
(e.g., cyclosporine, celecoxib and artemether, among others) the poor dissolution rate of these
compounds is responsible for the poor absorption from the GI tract.
• SNEDDS spontaneously present the drug in very fine nanodroplets offering very high surface
area for absorption. This helps with quick absorption of the drug and improves oral bioavailability.
 Poor permeability-Poor permeability is also one of the major factors that limits oral bioavailability
of several drugs, such as atenolol and acyclovir (BCS class III).
 several SNEDDS components have the ability to enhance the membrane permeation of the
therapeutic agents. For example, oily phases (e.g., oleic acid, monoglycerides of caprylic acid and
propylene glycol esters of caprylic acid [46]), surfactants (e.g., Labrasol®, vitamin E tocopheryl
polyethene glycol 1000 succinate [TPGS] and polysorbate 80 [75–77]) and cosurfactants (e.g.,
PEG 400, Transcutol and alcohol [78]) are known to have permeation enhancing properties

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 High degree of presystemic & hepatic first-pass metabolism- SNEDDS components
including Gelucire 44/14 (lauroyl macrogol glycerides) and Labrasol (caprylocaproyl
macrogol glycerides) have the ability to modulate/inhibit the activity of cytochrome P450
and gut metabolizing enzymes], whereas long-chain tri- and mono-glycerides (glyceryl
monooleate) have demonstrated the ability to improve the intestinal lymphatic transport of
the hydrophobic drugs.Both these mechanisms are responsible for reducing/preventing the
first-pass or presystemic metabolism of the drug resulting in the improvement of oral
bioavailability;

10. ADVANTAGES OF SNEDDS
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 Reduction in inter & intra-subject variability & food effects- The bioavailability of probucol is not
affected by the fed and fasted state in minipigs when administered as SNEDDS, whereas powder
formulation shows considerable variation in fed and fasted state bioavailability.
 Onset of action-SNEDDS can facilitate oral absorption of the drug, which would result in quick
onset of action. The comparative pharmacokinetic analysis of SNEDDS to conventional formulation
has demonstrated that there is considerable reduction observed in tmax (an indirect measure of
quick onset of action) in case of SNEDDS .
 Reduction in the drug dose-The ability of the SNEDDS in improving Cmax and oral bioavailability.
The improvement in bioavailability can be translated into reduction in the drug dose and dose-
related side effects of many hydrophobic drugs, such as antihypertensive and antidiabetic drugs.
 Ease of manufacture & scale-up-compared with other novel drug delivery systems, such as solid
dispersions, liposomes and nanoparticles. SNEDDS require very simple and economical
manufacturing facilities, such as simple mixer with an agitator and volumetric liquid filling
equipment for large-scale manufacturing.

11. DISADVANTAGES OF SNEDDS
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• Self-nanoemulsifying drug delivery systems, being liquid in nature, need to be delivered through
either soft/hard gelatin or hydroxypropylmethylcellulose capsules. There are few issues associated
with these systems when presented in capsules, such as incompatibility of components with the
capsule shell in the long term, precipitation of drugs during fabrication and storage at low
temperature and critical method of production, among others.
• SNEDDS may not be useful for hydrophobic drugs that can undergo pH catalyzed or solution-state
degradation. We observed that modified oily phases used for SNEDDS fabrication have acidic pH
owing to the presence of traces of free fatty acids. These acids can catalyze the degradation of pH-
sensitive drugs, such as cefpodoxime proxetil on long-term storage.
• simvastatin SNEDDS formulation was susceptible to hydrolytic degradation at accelerated
conditions of storage owing to reactive ester and lactone moiety and on long-term storage of
SNEDDS. In view of our experience, we believe that chemical stability of drugs in SNEDDS needs
to be studied at accelerated conditions.

12. FUTURE PERSPECTIVE
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Research on SNEDDS technology has accelerated in the
last 5 years and several reports have appeared in the
literature. SNEDDS have primarily been explored for
enhancement of bioavailability in oral drug delivery. The
pHcatalyzed and solution-state degradation of drugs in
SNEDDS needs to be evaluated. The conversion of
SNEDDS to a solid state can reduce drug degradation but
cannot eliminate it in many cases.
Considerable investigations have been carried out to
convert liquid SNEDDS to a solid dosage form such as
tablets and pellets. However, there is a need to identify a
suitable highly porous amphiphilic carrier that can convert
liquid SNEDDS into a solid powder without significant
increase in the volume or bulk density

13. REFERENCE
• Date AA, Desai N, Dixit R, Nagarsenker M. Self-
nanoemulsifying drug delivery systems: formulation insights,
applications and advances. Nanomedicine. 2010
Dec;5(10):1595-616.
• Rehman FU, Shah KU, Shah SU, Khan IU, Khan GM, Khan
A. From nanoemulsions to self-nanoemulsions, with recent
advances in self-nanoemulsifying drug delivery systems
(SNEDDS). Expert opinion on drug delivery. 2017 Nov
2;14(11):1325-40.
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14. THANK YOU
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