Gel is a soft solid which contains both solid & liquid components where the solid component (gelator) is present as a mesh/network of aggregates, which immobilizes the liquid component

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ORGANOGEL
Mr. Sagar Kishor Savale
[Department of Pharmaceutics]
avengersagar16@gmail.com
2015-2016
Department of Pharmacy (Pharmaceutics) | Sagar savale

2. CONTENTS
 Introduction
 Classification of Organogel
 Factors affecting gel formation
 Types of Organogel
 Applications
 Conclusions
 References

3. INTRODUCTION
 Gel – Contains both solid & liquid.
 Components of gel -Solid
-Liquid
-Drug.
 Thermoreversible.

4.  In the last decade, interest in organogels has grown rapidly with the
discovery and synthesis of a very large number of diverse
molecules, which can gel organic solvents at low concentrations.
 A simple working definition of the term ‘gel’ is a soft, solid or
solid-like material, which contains both solid and liquid
components, where the solid component (the gelator) is present as
a mesh/network of aggregates, which immobilises the liquid
component. This solid network prevents the liquid from flowing,
primarily via surface tension.

5.  The gel is said to be a hydrogel or an organogel depending on the
nature of the liquid component: water in hydrogels and an organic
solvent in organogels.
 However, only a few organogels are currently being studied as drug
delivery vehicles as most of the existing organogels are composed of
pharmaceutically unacceptable organic liquids and/or
unacceptable/untested gelators.
 In this seminar a brief overview of organogels is presented, followed
by a more in-depth review of the gels that have been investigated for
drug delivery.

6. Organogel
 Gel is a soft solid which contains both solid & liquid components
where the solid component (gelator) is present as a mesh/network
of aggregates, which immobilizes the liquid component
 The solid network prevents the liquid from flowing
 The gel is called as hydrogel or organogel depending on the nature
of the liquid component( water in hydrogels & an organic solvent
in organogels
 In hydrogels the gelator is a polymer while in case of organogel,
gelators are small molecules

7. Advantages
7
•Ease of administration.
•Avoids first pass effect.
•Absorption enhancement.
•Overcome the problems of conventional dosage forms.
•Site specific drug delivery.
•Avoid systemic adverse effects associated with oral
administration of drug.

8. Organogelators
 n-alkanes such as hexadecane & organic liquids
 Non ionic surfactant- sorbitan monostearate
 Steroids & their derivatives
 Anthranyl derivatives
 Macrocyclic gelators (calixarenes)

9. Organogel structure &
mechanism of organogelling
 The organogelling or gelation of lecithin solutions
in organic solvents is induced as a result of
incorporation of a polar solvent
 Lecithin when dissolved in nonpolar media alone ,
self assembles into reverse micelles.
 The growth of spherical reverse micelles & further
transformation into tubular & cylindrical micellar
aggregates (sphere to cylinder transformation) is
triggered by addition of small & critical amounts of
polar additive

10. CLASSIFICATION
 Nature of solvent
 Nature of Gelators
 Nature of IMI
The specific process leading to the formation of the gelling
matrix depends on the physicochemical properties of gel
components and their resulting interactions.

12. Organogel preparation
Gelators + Liquid phase
Heat
Organic Solution/dispersion
Cool
Gel
 Why heating and cooling ?
 Is this gel form or not ?

13.  Most of the organogels are prepared by heating a mixture of the gelator &
the liquid component to form organic solution/dispersion
 Heating allows dissolution of gelator in the liquid
 Following cooling, the solubility of gelator in the liquid phase decreases &
gelator-solvent interactions are reduced, which results in gelator molecules
coming out of solution
 Entanglement of the aggregates & connections among them result in the
formation of three dimensional network, which immobilizes the fluid phase
 The physical organogels, held together by noncovalent forces are
thermoreversible

14.  Following heating the gel melts to the sol phase as the gelator aggregates
dissolve in the organic liquid, whereas cooling the hot sol phase results in
gelation
 The temperature at which the sol-to-gel or gel-to-sol transition occurs is
called the gelation temp.
 The Tg of 10% w/v sorbitan monostearate is 41-440C
 Solutions of lecithin in an organic solvent such as iso-octane can be gelled
by the addition of trace amounts of a polar substance e.g. water ,glycerol,
ethylene glycol or formamide

15. Factors affecting gel formation
 Molecular shape of Solvent
Ex. SNO in t-Decalin ,Cyclohexane.
 Functional Group of solvent
Ex. CAB in 1-Octanol & n-alkens
 Presences/Addition of other component

16. TYPES OF ORGANOGEL
 Sorbitan Monostearate Organogels
 In Situ Formation Of An Organogel Of L-alanine Derivative
 Eudragit Organogels
 Microemulsion-based Gels
 Lecithin Organogels
 Pluronic Lecithin Organogels

17. Sorbitan Monostearate Organogels
 Sorbitan monostearate (Span 60) and sorbitan monopalmitate
(Span 40) have been found to gel a number of organic
solvents at low concentrations. They are prepared by heating
the gelator/liquid mixture in a water bath at 60°C (which
results in dispersion of the gelator in the liquid medium) and
cooling of the resulting suspension, following which the latter
sets to an opaque, white, semisolid gel.
 Sorbitan monostearate molecules are arranged in inverted bilayers within
the tubules, as shown in Figure.
Sorbitan Monostearate Organogel

18.  The tubules form a three-dimensional network, which immobilizes the liquid, and hence
a gel is formed.
 Sorbitan monostearate gels has been investigated as delivery vehicles for hydrophilic
vaccines

19. L-alanine derivative Organogel
LAM + O.S. + Soyabin oil
Gel
Addition of ethanol – Form solution.
(Used as Sustained released implant)

20. Eudragit Organogel
Drug + Polyhydric Alcohol ( PG )
Pour into
Eudragit L or S Solution (30 to 40%)
 Gelling property – Vary.

21. Micro emulsion based
 Gelatin is used as Gelator.
2-(ethylhexyl) Na Sulfosuccinates + Isooctane
hot water
Gelatin

22. Lecithin Organogel
Lecithin + O.S.
Polar Solvent
Gel
 Water: Lecithin (2:10)
 Incorporate both types of drugs
 small amt. of water requied
 long chain, short chain

23. Figure 1. Schematic diagram of the preparation of lecithin organogels.
Note: Lipophilic drugs are solubilized in the organic phase (stage 1),
whereas hydrophilic compounds can be solubilized in the polar phase
(stage 2). For the preparation of pluronic lecithin organogel (PLO gel),
the co-surfactant pluronic is taken along with polar phase (stage 2).

24. Table 1. Various Salient Features of Lecithin Organogels
Salient Features
Template vehicle LOs provide opportunities for incorporation of a wide range of
substances with diverse physicochemical characters (e.g. chemical
nature, solubility, molecular weight, size)
Process benefits Spontaneity of organogel formation, by virtue of self-assembled
supramolecular arrangement of surfactant molecules, makes the
process very simple and easy to handle.
Structural/physical
stability
Being thermodynamically stable, the structural integrity of LOs is
maintained for longer time periods.
Chemical stability LOs are moisture insensitive, and being organic in character, they also
resist microbial contamination.
Topical delivery
potential
 Being well balanced in hydrophilic and lipophilic character, they can
efficiently partition with the skin and therefore enhance the skin
penetration and transport of the molecules.
 LOs also provide the desired hydration of skin in a lipid-enriched
environment so as to maintain the bioactive state of skin.
Safety Use of biocompatible, biodegradable, and non immunogenic materials
makes them safe for long term applications.

25. Pluronic lecithin organogel
 PLO is an opaque, yellow gel, composed of isopropyl
palmitate, soy lecithin, water and the hydrophilic polymer,
Pluronic F127. The difference between PLO and its precursor,
lecithin gels, is the presence of Pluronic F127 (a hydrophilic
polymer that gels water) and the greater amount of water
compared with the oi
 PLO gel looks and feels like a cream but is actually a gel.
When the aqueous phase (pluronic gel) is combined with the
lecithin oil base creates an emulsion that forms together due to
the pluronic gel and the viscosity of that gel at room
temperature.

26.  PLO has been shown in vivo and in vitro to modulate the
release and permeation of drugs applied transdermally.
 It improves the topical administration of drug mainly due to
the desired drug partitioning, biphasic drug solubility and the
modification of skin barrier system by organogel components.
 It shows low skin irritation, increases patient compliance,
reduces side effects, avoids first pass metabolism and
increases efficiency of drug.

27.  Despite the large abundance and variety of organogels systems,
relatively few have current applications in drug delivery, owing
mostly to the lack of information on the biocompatibility and
toxicity of organogelator molecules and their degradation
products. This review focuses on organogel systems that have
been geared towards pharmaceutical applications and are at
various stages of development, from preliminary in vitro
experiments to clinical studies.
Table I provides a summary of the key drug delivery studies
conducted using organogels.
Organogels In Drug Delivery

28. Table I: Organogel Formulations Used In Drug Delivery
Sr.No. Types Route of
administration
Study conducted Model drugs
1 Lecithin Transdermal  Clinical trials
 In vivo skin
permeation & efficacy
 In vitro skin
Permeation
 In vitro release
 Diclofenac
 Piroxicam, tetrabenzamidine
 Scopolamine and boxaterol
Propranolol, nicardipine
 Aceclofenac, indomethacin &
Diclofenac
2 Sorbitan
monostearate
(SMS)
 Nasal
 Oral
 Subcutaneous &
intramuscular
 In vitro release
 In vitro release
 In vivo efficacy
 Propranolol
 Cyclosporin A
 BSA1 and HA2
3 PLOs Transdermal  Clinical trials
 In vivo skin permeation
& efficacy
 In vitro release
Promethazine, Ondansetron &
Diclofenac
Methimazole, Fluoxetine,
Dexamethazone, Amitriptyline,
Methadone, Morphine,
Buprenorphine & Buspirone
Scopolamine, Metoclopramide,
Haloperidol & Prochlorperazine

29. Sr.No Types Route of
administration
Study conducted Model drugs
4 L-alanine
derivative
Subcutaneous  In vitro/in vivo
release
 In vitro/in vivo
release
and efficacy
 Rivastigmine
 Leuprolide
5 Eudragit
organoges
 Rectal
 Buccal
 In vivo efficacy
 In vivo efficacy
 Salicylic acid
 BSA

30.  In contrast to the ease of preparation, characterization of organogels is
relatively complicated on account of their interior structural design build-up
on the self-associated supramolecules.
 These microstructures, the result of varied polar-nonpolar interactions, are
highly sensitive and pose difficulties in the investigative studies. However,
different characterization studies are extremely useful while investigating the
potential applications of organogel systems as a topical vehicle.
 It has been reported that many of the physicochemical properties of
organogels viz Rheological behavior, physical and mechanical stability and
drug release behavior are dependent upon how molecules arrange themselves
to provide the specific structural network within the organogel system.
Characterization of Organogels

31.  Gelation Studies
 Rheological Behavior
 Structural Features
 Phase Transition Temperatures
 Gel Strength
 Water Content
 Percentage Drug Content
 In-vitro / Permeation Study
 In-vivo Study
 Stability Study
Evaluation Of Organogels

32.  Gelation Studies:-A simple visual test to determine whether
gelation has taken place involves inverting the reaction vessel,
gelation has occurred if the sample does not flow
 Rheological Behavior:- are viscoelastic in nature, prior to
gelling exhibit Newtonian behavior & follows viscoelastic
behavior on addition of polar phase. It has been observed that
increasing the gelatos conc. leads to increase in the viscosity &
hence gel strength
 Structural features:-Molecular architecture of organogels has
been evaluated using NMR spectroscopy, hydrogen bonding
has been established by FTIR spectroscopy. The knowledge of
molecular packing within organogel network has been
obtained using scanning & transmission electron microscopy

33.  Phase transition Temperature:- gives insight into the nature
of microstructures that form the gelling cross linked network.
A narrow PTT range(3-50C) is indicative of homogeneous
microstructures within the gel. It is determined by hot stage
microscopy (HST)& high sensitivity DCS
 Gelation study:-A simple visual test to determine
whether gelation has taken place involves inverting the
reaction vessel; gelation is said to occurred if the
sample does not flow.
 Water Content:-water loss by evaporation can lead to
decrease in viscisity thus affecting the gel stability. Near
infrared spectroscopy(NIR,1800-2200) is used for determining
water content

34. Stability study:-
The organogels were tested under following
condition of temperature and relative humidity.
 25°C ± 2°C at 75 ± 5% RH
 40°C ± 2°C at 75 ± 5% RH
In vitro study:-
The formulation is subjected to in vitro diffusion
through dialysis membrane.
 In vivo study:-
Carrageenan induce rat paw edema method was
used as a model.

35.  The site of application can drastically affect the
distribution and absorption of a drug.
 If a systemic effect is desired, the gel should be
applied to neck, inner thigh, or inner wrist area.
 For a local effect, the gel should be applied directly to
the joint or painful region, then rub in well
Area of Application

36.  Ease of preparation & scale up, easier quality monitoring, thermodynamic
stability, enhanced topical performance, biocompatibility, safety upon
applications for prolonged period make the organogels a vehicle of choice for
topical drug delivery
 Ease of administration.
 Site specific drug delivery.
 Avoids first pass effect.
 Absorption enhancement.
 Overcome the problems of conventional dosage forms.
Application

37. Limitation
 The major limitation in the formation of Los is the requirement
of high purity lecithins
 High purity lecithin is expensive
 Difficult to obtain in large quantities
 Inclusion of pluronics as cosurfectant makes organogelling
feasible with lecithin of relatively less purity

38. Conclusions
 Very Few Organogels are used in drug delivery -
Component of Organogel are not pharmaceutically
acceptable.
 LO – good for TDDs
 Eudragit gel – Under investigation.
 LAM – used as Implant.

39. References
 Murdan S. Organogels in drug delivery, Expert Opin Drug Deliv ,
2(3), 2005,p.489-505.
 Anda V., Leroux J. , Organogels and Their Use in Drug Delivery - A
Review, Journal of Controlled Release, Accepted 27 September
2007,p. 18-59.
 Kumar R and Katare OP. Lecithin organogels as a potential
phospholipid-structured system for topical drug delivery: a review,
AAPS PharmaSciTech, 6(2), 2005,p. 298-310.
 Murdan S. A review of pluronic lecithin organogel as a topical and
transdermal drug delivery system, Hospital Pharmacist, 12, 2005, p.
267-270.
 Shchipunov YA. Lecithin organogel: a micellar system with unique
properties, Colloids and Surfaces: A Physicochemical and Engineering
Aspects, 183-185, 2001, p. 541-554.

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