ORGANOGELORGANOGELPresented by:

Chinchole Pravin Sonu(M.PHARM 2nd SEM)

DEPARTMENT OF PHARMACEUTICS & QUALITY ASSURANCE

R. C. Patel Institute of Pharmaceutical Education and Research, shirpur.

CONTENTSCONTENTS IntroductionIntroduction

Types Of OrganogelTypes Of Organogel

Organogels In Drug DeliveryOrganogels In Drug Delivery

Characterisation Of OrganogelCharacterisation Of Organogel

Area Of ApplicationArea Of Application

Applications Applications

ConclusionConclusion

Reference Reference

INTRODUCTIONINTRODUCTION In the last decade, interest in organogels has grown rapidly with In the last decade, interest in organogels has grown rapidly with

the discovery and synthesis of a very large number of diverse the discovery and synthesis of a very large number of diverse molecules, which can gel organic solvents at low concentrations. molecules, which can gel organic solvents at low concentrations.

A simple working definition of the term ‘gel’ is a soft, solid or A simple working definition of the term ‘gel’ is a soft, solid or solid-like material, which contains both solid and liquid solid-like material, which contains both solid and liquid components, where the solid component (the gelator) is present as components, where the solid component (the gelator) is present as a mesh/network of aggregates, which immobilises the liquid a mesh/network of aggregates, which immobilises the liquid component. This solid network prevents the liquid from flowing, component. This solid network prevents the liquid from flowing, primarily via surface tension.primarily via surface tension.

The gel is said to be a hydrogel or an organogel depending on the 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 nature of the liquid component: water in hydrogels and an organic solvent in organogels.solvent in organogels.

However, only a few organogels are currently being studied as drug However, only a few organogels are currently being studied as drug delivery vehicles as most of the existing organogels are composed delivery vehicles as most of the existing organogels are composed of pharmaceutically unacceptable organic liquids and/or of pharmaceutically unacceptable organic liquids and/or unacceptable/untested gelators. unacceptable/untested gelators.

In this seminar a brief overview of organogels is presented, In this seminar a brief overview of organogels is presented, followed by a more in-depth review of the gels that have been followed by a more in-depth review of the gels that have been investigated for drug delivery.investigated for drug delivery.

OrganogelOrganogel

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

The solid network prevents the liquid from flowingThe solid network prevents the liquid from flowing

The gel is called as hydrogel or organogel depending on the nature of the liquid The gel is called as hydrogel or organogel depending on the nature of the liquid component( water in hydrogels & an organic solvent in organogelscomponent( water in hydrogels & an organic solvent in organogels

In hydrogels the gelator is a polymer while in case of organogel, gelators are In hydrogels the gelator is a polymer while in case of organogel, gelators are small moleculessmall molecules

OrganogelatorsOrganogelators

n-alkanes such as hexadecane & organic liquidsn-alkanes such as hexadecane & organic liquids

Non ionic surfactant- sorbitan monostearateNon ionic surfactant- sorbitan monostearate

Steroids & their derivativesSteroids & their derivatives

Anthranyl derivativesAnthranyl derivatives

Macrocyclic gelators (calixarenes)Macrocyclic gelators (calixarenes)

Gel preparationGel preparation

Most of the organogels are prepared by heating a mixture of the gelator & Most of the organogels are prepared by heating a mixture of the gelator & the liquid component to form organic solution/dispersionthe liquid component to form organic solution/dispersion

Heating allows dissolution of gelator in the liquidHeating allows dissolution of gelator in the liquid

Following cooling, the solubility of gelator in the liquid phase decreases & Following cooling, the solubility of gelator in the liquid phase decreases & gelator-solvent interactions are reduced, which results in gelator molecules gelator-solvent interactions are reduced, which results in gelator molecules coming out of solutioncoming out of solution

Entanglement of the aggregates & connections among them result in the Entanglement of the aggregates & connections among them result in the formation of three dimensional network, which immobilizes the fluid formation of three dimensional network, which immobilizes the fluid phasephase

The physical organogels, held together by noncovalent forces are The physical organogels, held together by noncovalent forces are thermoreversiblethermoreversible

Following heating the gel melts to the sol phase as the gelator aggregates 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 dissolve in the organic liquid, whereas cooling the hot sol phase results in gelationgelation

The temperature at which the sol-to-gel or gel-to-sol transition occurs is The temperature at which the sol-to-gel or gel-to-sol transition occurs is called the gelation temp.called the gelation temp.

The The TgTg of 10% w/v sorbitan monostearate is of 10% w/v sorbitan monostearate is 41-4441-4400CC

Solutions of lecithin in an organic solvent such as iso-octane can be gelled 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, by the addition of trace amounts of a polar substance e.g. water ,glycerol, ethylene glycol or formamideethylene glycol or formamide

Organogel structure & mechanism of organogellingOrganogel structure & mechanism of organogelling

The organogelling or gelation of lecithin solutions in organic The organogelling or gelation of lecithin solutions in organic solvents is induced as a result of incorporation of a polar solvents is induced as a result of incorporation of a polar solventsolvent

Lecithin when dissolved in nonpolar media alone , self Lecithin when dissolved in nonpolar media alone , self assembles into reverse micelles.assembles into reverse micelles.

The growth of spherical reverse micelles & further The growth of spherical reverse micelles & further transformation into tubular & cylindrical micellar aggregates transformation into tubular & cylindrical micellar aggregates (sphere to cylinder transformation) is triggered by addition of (sphere to cylinder transformation) is triggered by addition of small & critical amounts of polar additivesmall & critical amounts of polar additive

The specific process leading to the formation of the gelling matrix depends on the The specific process leading to the formation of the gelling matrix depends on the physicochemical properties of gel components and their resulting interactions. physicochemical properties of gel components and their resulting interactions. Figure 1Figure 1 presents a flow-chart compiling various accepted classifications of gels based on the presents a flow-chart compiling various accepted classifications of gels based on the nature of solvents, gelators, and intermolecular interactions.nature of solvents, gelators, and intermolecular interactions.

TYPES OF ORGANOGELTYPES OF ORGANOGEL Sorbitan Monostearate OrganogelsSorbitan Monostearate Organogels

In Situ Formation Of An Organogel Of L-alanine DerivativeIn Situ Formation Of An Organogel Of L-alanine Derivative

Eudragit OrganogelsEudragit Organogels

Microemulsion-based GelsMicroemulsion-based Gels

Lecithin OrganogelsLecithin Organogels

Pluronic Lecithin OrganogelsPluronic Lecithin Organogels

Sorbitan Monostearate OrganogelsSorbitan Monostearate Organogels Sorbitan monostearate Sorbitan monostearate (Span 60)(Span 60) and sorbitan monopalmitate and sorbitan monopalmitate (Span 40)(Span 40)

have been found to gel a number of organic solvents at low concentrations. have been found to gel a number of organic solvents at low concentrations. They are prepared by They are prepared by heating the gelator/liquid mixtureheating the gelator/liquid mixture in a water bath in a water bath at 60°C (which results in dispersion of the gelator in the liquid medium) at 60°C (which results in dispersion of the gelator in the liquid medium) and and cooling cooling of the resulting suspension, following which the latter sets to of the resulting suspension, following which the latter sets to an opaque, white, an opaque, white, semisolid gel.semisolid gel.

Sorbitan monostearate molecules are arranged in inverted bilayers within Sorbitan monostearate molecules are arranged in inverted bilayers within the tubules, as shown in the tubules, as shown in Figure.Figure.

The tubules form a three-dimensional network, which immobilizes the liquid, and hence The tubules form a three-dimensional network, which immobilizes the liquid, and hence a gel is formed.a gel is formed.

Sorbitan monostearate gels has been investigated as delivery vehicles for hydrophilic Sorbitan monostearate gels has been investigated as delivery vehicles for hydrophilic vaccinesvaccines

In Situ Formation Of An Organogel Of L-alanine DerivativeIn Situ Formation Of An Organogel Of L-alanine Derivative In situ L-alanine derivative organogel is prepared from N-lauroyl-L-alanine In situ L-alanine derivative organogel is prepared from N-lauroyl-L-alanine

methyl ester (LAM) which gels in the pharmaceutically acceptable organic methyl ester (LAM) which gels in the pharmaceutically acceptable organic solvents such as soybean oil and medium-chain triglycerides. solvents such as soybean oil and medium-chain triglycerides.

Normally, the system exists in the gel state at room temperature but on the Normally, the system exists in the gel state at room temperature but on the addition of ethanol to a gelator/solvent solution it inhibits gelation because the addition of ethanol to a gelator/solvent solution it inhibits gelation because the ethanol disrupts the formation of hydrogen bonds (essential for gelator self-ethanol disrupts the formation of hydrogen bonds (essential for gelator self-assembly into aggregates) between the gelator molecules. This means that a assembly into aggregates) between the gelator molecules. This means that a solution of LAM in an organic solvent can remain in the sol phase at room solution of LAM in an organic solvent can remain in the sol phase at room temperature when some ethanol is added to the mixture. temperature when some ethanol is added to the mixture.

When such a sol phase (20% LAM plus 14% ethanol in soybean oil) was When such a sol phase (20% LAM plus 14% ethanol in soybean oil) was placed in phosphate buffered saline at 37°C it turned into an opaque gel within placed in phosphate buffered saline at 37°C it turned into an opaque gel within 2 min as the hydrophilic ethanol diffused away into the aqueous buffer, and as 2 min as the hydrophilic ethanol diffused away into the aqueous buffer, and as gelator–gelator hydrogen bonds were formed. gelator–gelator hydrogen bonds were formed.

Thus, theoretically, such a LAM/ethanol/soybean oil solution could form gels in situ Thus, theoretically, such a LAM/ethanol/soybean oil solution could form gels in situ following its subcutaneous injection, due to ethanol diffusion away from the following its subcutaneous injection, due to ethanol diffusion away from the formulation, into the surrounding tissues.formulation, into the surrounding tissues.

The main advantage of in situ forming gels is their injectability at room temperature. The main advantage of in situ forming gels is their injectability at room temperature. Once a drug-containing gel is formed in situ, it could act as a sustained-release implantOnce a drug-containing gel is formed in situ, it could act as a sustained-release implant

Eudragit OrganogelEudragit Organogel

Eudragit organogels are different from the organogels they are the mixtures of Eudragit (L Eudragit organogels are different from the organogels they are the mixtures of Eudragit (L or S) and polyhydric alcohols, such as glycerol, propylene glycol and liquid polyethylene or S) and polyhydric alcohols, such as glycerol, propylene glycol and liquid polyethylene glycol, containing high concentrations (30 or 40% w/w) of Eudragit.glycol, containing high concentrations (30 or 40% w/w) of Eudragit.

Drug-containing gels were prepared by dissolving the drug (salicylic acid, sodium Drug-containing gels were prepared by dissolving the drug (salicylic acid, sodium

salicylate, procain or ketoprofen) in propylene glycol, pouring the resulting solution into salicylate, procain or ketoprofen) in propylene glycol, pouring the resulting solution into Eudragit powder (contained in a mortar), and immediately mixing with a pestle for 1 min.Eudragit powder (contained in a mortar), and immediately mixing with a pestle for 1 min.

Gel viscosity was found to increase with increasing concentrations of Eudragit and to Gel viscosity was found to increase with increasing concentrations of Eudragit and to decrease with increasing drug content. The drug content in Eudragit organogels should be decrease with increasing drug content. The drug content in Eudragit organogels should be kept low (e.g., 1.25% w/w) to maintain gel rigidity and stability.kept low (e.g., 1.25% w/w) to maintain gel rigidity and stability.

The mechanism of drug release from Eudragit L and S organogels was due to surface The mechanism of drug release from Eudragit L and S organogels was due to surface erosion of the Eudragit L and diffusion through the Eudragit S gel matrix. erosion of the Eudragit L and diffusion through the Eudragit S gel matrix.

Drug release from Eudragit S organogel thus increased with increasing temperature and Drug release from Eudragit S organogel thus increased with increasing temperature and agitation rate of the release medium.agitation rate of the release medium.

Microemulsion-based GelsMicroemulsion-based Gels Microemulsion-based gels (MBGs) are also different from most organogels in that the Microemulsion-based gels (MBGs) are also different from most organogels in that the

gelator, gelatin, is a hydrophilic polymer, which gels water. gelator, gelatin, is a hydrophilic polymer, which gels water.

MBGs were initially prepared by dissolving solid gelatin in a hot w/o microemulsion MBGs were initially prepared by dissolving solid gelatin in a hot w/o microemulsion (which was composed of water, AOT and isooctane) followed by cooling.(which was composed of water, AOT and isooctane) followed by cooling.

In MBGs, the gelatin would dissolve in the water droplets of the w/o microemulsion and In MBGs, the gelatin would dissolve in the water droplets of the w/o microemulsion and that cooling of the system would result in gelation of the water droplets, which would that cooling of the system would result in gelation of the water droplets, which would lead to clouding of the system and possibly phase separation. Thus microemulsion lead to clouding of the system and possibly phase separation. Thus microemulsion gelled to a transparent semisolid with a high viscosity and a high electro-conductivity.gelled to a transparent semisolid with a high viscosity and a high electro-conductivity.

Lecithin OrganogelsLecithin Organogels Lecithin Organogels (Los) are thermodynamically stable, clear, viscoelastic, Lecithin Organogels (Los) are thermodynamically stable, clear, viscoelastic,

biocompatible, and isotropic gels composed of phospholipids (lecithin), biocompatible, and isotropic gels composed of phospholipids (lecithin), appropriate organic solvent, and a polar solventappropriate organic solvent, and a polar solvent

LOs, the jelly-like phases, consist of a 3-dimensional network of entangled LOs, the jelly-like phases, consist of a 3-dimensional network of entangled reverse cylindrical (polymer-like) micelles, which immobilizes the continuous or reverse cylindrical (polymer-like) micelles, which immobilizes the continuous or macroscopic external organic phase, thus turning a liquid into a gel.macroscopic external organic phase, thus turning a liquid into a gel.

A lecithin organogel is formed when small amounts of water or other polar A lecithin organogel is formed when small amounts of water or other polar substances, such as glycerol, ethylene glycol or formamide, are added to a substances, such as glycerol, ethylene glycol or formamide, are added to a nonaqueous solution of lecithin.nonaqueous solution of lecithin.

The molar ratio of water to lecithin (w0 = [H2O]/[lecithin]) is typically 2:10 and The molar ratio of water to lecithin (w0 = [H2O]/[lecithin]) is typically 2:10 and depends on the nature of the organic solvent. Excess water leads to destabilization depends on the nature of the organic solvent. Excess water leads to destabilization of the gel and phase separation.of the gel and phase separation.

Lecithin organogels have been used as carriers for hydrophilic and hydrophobic Lecithin organogels have been used as carriers for hydrophilic and hydrophobic drug molecules. Hydrophobic drugs are dissolved in the oil phase (lecithin plus drug molecules. Hydrophobic drugs are dissolved in the oil phase (lecithin plus organic solvent), whereas hydrophilic molecules are dissolved in water, which is organic solvent), whereas hydrophilic molecules are dissolved in water, which is then added to an organic solution of lecithin to induce gelation.then added to an organic solution of lecithin to induce gelation.

Soy or egg lecithin in the conc. range of 50-200 mM in different organic Soy or egg lecithin in the conc. range of 50-200 mM in different organic solvents such as linear or cyclic alkanes, esters of fatty acids & amides was solvents such as linear or cyclic alkanes, esters of fatty acids & amides was noted to be effective for gel formationnoted to be effective for gel formation

It was observed that addition of trace amounts of water into nonaqueous It was observed that addition of trace amounts of water into nonaqueous solutions of soy lecithin(50-200 mM) caused an abrupt rise in solutions of soy lecithin(50-200 mM) caused an abrupt rise in viscosity(10viscosity(1044-10-1066 times) times)

The transfer of jelly like state has been demonstrated only for nonaqueous The transfer of jelly like state has been demonstrated only for nonaqueous solutions of naturally occuring unsaturated lecithinssolutions of naturally occuring unsaturated lecithins

Synthetic lecithins containing residues of saturated fatty acids failed to Synthetic lecithins containing residues of saturated fatty acids failed to form organogel. Lecithin should contain 95% phosphatidylcholineform organogel. Lecithin should contain 95% phosphatidylcholine

Organic solvents which have gelling property are fatty acids& amines, Organic solvents which have gelling property are fatty acids& amines, ethyl myristate, IPM,IPP (biocompatible, biodegradable,skin penetration ethyl myristate, IPM,IPP (biocompatible, biodegradable,skin penetration enhancing property), ethers & esters, cyclopentane, linear,branched,& enhancing property), ethers & esters, cyclopentane, linear,branched,& cyclic alkanescyclic alkanes

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).

Table 1.Table 1. Various Salient Features of Lecithin Organogels Various Salient Features of Lecithin Organogels

Salient FeaturesSalient Features

Template vehicleTemplate vehicle LOs provide opportunities for incorporation of a wide range of LOs provide opportunities for incorporation of a wide range of substances with diverse physicochemical characters (e.g. chemical substances with diverse physicochemical characters (e.g. chemical nature, solubility, molecular weight, size)nature, solubility, molecular weight, size)

Process benefitsProcess benefits Spontaneity of organogel formation, by virtue of self-assembled Spontaneity of organogel formation, by virtue of self-assembled supramolecular arrangement of surfactant molecules, makes the supramolecular arrangement of surfactant molecules, makes the process very simple and easy to handle.process very simple and easy to handle.

Structural/physical Structural/physical stabilitystability

Being thermodynamically stable, the structural integrity of LOs is Being thermodynamically stable, the structural integrity of LOs is maintained for longer time periods.maintained for longer time periods.

Chemical stabilityChemical stability LOs are moisture insensitive, and being organic in character, they also LOs are moisture insensitive, and being organic in character, they also resist microbial contamination.resist microbial contamination.

Topical deliveryTopical deliverypotentialpotential

Being well balanced in hydrophilic and lipophilic character, they Being well balanced in hydrophilic and lipophilic character, they can efficiently partition with the skin and therefore enhance the skin can efficiently partition with the skin and therefore enhance the skin penetration and transport of the molecules.penetration and transport of the molecules. LOs also provide the desired hydration of skin in a lipid-enriched LOs also provide the desired hydration of skin in a lipid-enriched environment so as to maintain the bioactive state of skin.environment so as to maintain the bioactive state of skin.

SafetySafety Use of biocompatible, biodegradable, and non immunogenic materials Use of biocompatible, biodegradable, and non immunogenic materials makes them safe for long term applications.makes them safe for long term applications.

Pluronic Lecithin OrganogelsPluronic Lecithin Organogels PLO is an opaque, yellow gel, composed of isopropyl palmitate, soy PLO is an opaque, yellow gel, composed of isopropyl palmitate, soy

lecithin, water and the hydrophilic polymer, Pluronic F127. The difference lecithin, water and the hydrophilic polymer, Pluronic F127. The difference between PLO and its precursor, lecithin gels, is the presence of Pluronic between PLO and its precursor, lecithin gels, is the presence of Pluronic F127 (a hydrophilic polymer that gels water) and the greater amount of F127 (a hydrophilic polymer that gels water) and the greater amount of water compared with the oil.water compared with the oil.

PLO gel looks and feels like a cream but is actually a gel. When the 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 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 an emulsion that forms together due to the pluronic gel and the viscosity of that gel at room temperature.that gel at room temperature.

PLO has been shown in vivo and in vitro to modulate the PLO has been shown in vivo and in vitro to modulate the release and permeation of drugs applied transdermally.release and permeation of drugs applied transdermally.

It improves the topical administration of drug mainly due to It improves the topical administration of drug mainly due to the desired drug partitioning, biphasic drug solubility and the the desired drug partitioning, biphasic drug solubility and the modification of skin barrier system by organogel components.modification of skin barrier system by organogel components.

It shows low skin irritation, increases patient compliance, It shows low skin irritation, increases patient compliance, reduces side effects, avoids first pass metabolism and reduces side effects, avoids first pass metabolism and increases efficiency of drug. increases efficiency of drug.

Organogels In Drug DeliveryOrganogels In Drug Delivery Despite the large abundance and variety of organogel systems, relatively few Despite the large abundance and variety of organogel systems, relatively few

have current applications in drug delivery, owing mostly to the lack of have current applications in drug delivery, owing mostly to the lack of information on the biocompatibility and toxicity of organogelator molecules information on the biocompatibility and toxicity of organogelator molecules and their degradation products. This review focuses on organogel systems and their degradation products. This review focuses on organogel systems that have been geared towards pharmaceutical applications and are at that have been geared towards pharmaceutical applications and are at various stages of development, from preliminary in vitro experiments to various stages of development, from preliminary in vitro experiments to clinical studies. clinical studies.

Table ITable I provides a summary of the key drug delivery studies conducted provides a summary of the key drug delivery studies conducted using organogels.using organogels.

Table I: Organogel Formulations Used In Drug DeliveryTable I: Organogel Formulations Used In Drug Delivery

Sr.No.Sr.No. Types Types Route ofRoute ofadministrationadministration

Study conductedStudy conducted Model drugsModel drugs

11 LecithinLecithin TransdermalTransdermal Clinical trialsClinical trials In vivo skin In vivo skin permeation & efficacypermeation & efficacy In vitro skin In vitro skin PermeationPermeation In vitro releaseIn vitro release

DiclofenacDiclofenac Piroxicam, tetrabenzamidinePiroxicam, tetrabenzamidine

Scopolamine and boxaterolScopolamine and boxaterol Propranolol, nicardipinePropranolol, nicardipine Aceclofenac, indomethacin & Aceclofenac, indomethacin & DiclofenacDiclofenac

22 SorbitanSorbitanmonostearatemonostearate

(SMS)(SMS)

NasalNasal OralOral Subcutaneous & Subcutaneous & intramuscularintramuscular

In vitro releaseIn vitro release In vitro releaseIn vitro release In vivo efficacyIn vivo efficacy

PropranololPropranolol Cyclosporin ACyclosporin A BSABSA11 and HA and HA22

33 PLOsPLOs Transdermal Transdermal Clinical trialsClinical trials

In vivo skin permeationIn vivo skin permeation & efficacy& efficacy

In vitro releaseIn vitro release

Promethazine, Ondansetron &Promethazine, Ondansetron &DiclofenacDiclofenacMethimazole, Fluoxetine,Methimazole, Fluoxetine,Dexamethazone, Amitriptyline,Dexamethazone, Amitriptyline,Methadone, Morphine,Methadone, Morphine,Buprenorphine & BuspironeBuprenorphine & BuspironeScopolamine, Metoclopramide,Scopolamine, Metoclopramide,Haloperidol & ProchlorperazineHaloperidol & Prochlorperazine

Sr.NoSr.No Types Types Route ofRoute ofadministrationadministration

Study conductedStudy conducted Model drugsModel drugs

44 L-alanine L-alanine derivativederivative

SubcutaneousSubcutaneous In vitro/in vivo In vitro/in vivo releaserelease In vitro/in vivo In vitro/in vivo release release and efficacyand efficacy

RivastigmineRivastigmine LeuprolideLeuprolide

55 Eudragit Eudragit organogesorganoges

RectalRectal BuccalBuccal

In vivo efficacyIn vivo efficacy In vivo efficacyIn vivo efficacy

Salicylic acidSalicylic acid BSABSA

Characterization Of OrganogelsCharacterization Of Organogels

In contrast to the ease of preparation, characterization of organogels is In contrast to the ease of preparation, characterization of organogels is relatively complicated on account of their interior structural design build-up relatively complicated on account of their interior structural design build-up on the self-associated supramolecules. on the self-associated supramolecules.

These microstructures, the result of varied polar-nonpolar interactions, are These microstructures, the result of varied polar-nonpolar interactions, are highly sensitive and pose difficulties in the investigative studies. However, highly sensitive and pose difficulties in the investigative studies. However, different characterization studies are extremely useful while investigating the different characterization studies are extremely useful while investigating the potential applications of organogel systems as a topical vehicle. potential applications of organogel systems as a topical vehicle.

It has been reported that many of the physicochemical properties of It has been reported that many of the physicochemical properties of organogels viz Rheological behavior, physical and mechanical stability and organogels viz Rheological behavior, physical and mechanical stability and drug release behavior are dependent upon how molecules arrange themselves drug release behavior are dependent upon how molecules arrange themselves to provide the specific structural network within the organogel system.to provide the specific structural network within the organogel system.

Gelation StudiesGelation Studies Rheological BehaviorRheological Behavior Structural FeaturesStructural Features Phase Transition TemperaturesPhase Transition Temperatures Gel StrengthGel Strength Water ContentWater Content Percentage Drug ContentPercentage Drug Content In-vitro / Permeation StudyIn-vitro / Permeation Study In-vivo StudyIn-vivo Study Stability StudyStability Study

Evaluation Of Organogels Evaluation Of Organogels

Gelation StudiesGelation Studies:-A simple visual test to determine whether :-A simple visual test to determine whether gelation has taken place involves inverting the reaction gelation has taken place involves inverting the reaction vessel,gelation has occurred if the sample does not flowvessel,gelation has occurred if the sample does not flow

Rheological BehaviorRheological Behavior:- are viscoelastic in nature, prior to :- are viscoelastic in nature, prior to gelling exhibit Newtonian behavior & follows viscoelastic gelling exhibit Newtonian behavior & follows viscoelastic behavior on addition of polar phase. It has been observed that behavior on addition of polar phase. It has been observed that increasing the gelator conc. leads to increase in the viscosity & increasing the gelator conc. leads to increase in the viscosity & hence gel strengthhence gel strength

Structural featuresStructural features:-Molecular architecture of organogels has :-Molecular architecture of organogels has been evaluated using NMR spectroscopy, hydrogen bonding been evaluated using NMR spectroscopy, hydrogen bonding has been established by FTIR spectroscopy. The knowledge of has been established by FTIR spectroscopy. The knowledge of molecular packing within organogel network has been molecular packing within organogel network has been obtained using scanning & transmission electron microscopyobtained using scanning & transmission electron microscopy

Phase transition Temperature:-Phase transition Temperature:- gives insight into the nature of gives insight into the nature of microstructures that form the gelling cross linked network. A narrow PTT microstructures that form the gelling cross linked network. A narrow PTT range(3-5range(3-500C) is indicative of homogeneous microstructures within the gel. C) is indicative of homogeneous microstructures within the gel. It is determined by hot stage microscopy (HST)& high sensitivity DCS It is determined by hot stage microscopy (HST)& high sensitivity DCS

Gel strength:-Gel strength:-

Water ContentWater Content:-water loss by evaporation can lead to decrease in viscisity :-water loss by evaporation can lead to decrease in viscisity thus affecting the gel stability. Near infrared spectroscopy(NIR,1800-2200) thus affecting the gel stability. Near infrared spectroscopy(NIR,1800-2200) is used for determining water contentis used for determining water content

Area Of ApplicationArea Of Application

The site of application can drastically affect the distribution The site of application can drastically affect the distribution and absorption of a drug.and absorption of a drug.

If a systemic effect is desired, the gel should be applied to If a systemic effect is desired, the gel should be applied to neck, inner thigh, or inner wrist area.neck, inner thigh, or inner wrist area.

For a local effect, the gel should be applied directly to the joint For a local effect, the gel should be applied directly to the joint or painful region, then rub in wellor painful region, then rub in well

ApplicationApplication Ease of preparation & scale up, easier quality monitoring, thermodynamic Ease of preparation & scale up, easier quality monitoring, thermodynamic

stability, enhanced topical performance, biocompatibility, safety upon stability, enhanced topical performance, biocompatibility, safety upon applications for prolonged period make the organogels a vehicle of choice for applications for prolonged period make the organogels a vehicle of choice for topical drug deliverytopical drug delivery

Ease of administration.Ease of administration.

Site specific drug delivery.Site specific drug delivery.

Avoids first pass effect.Avoids first pass effect.

Absorption enhancement.Absorption enhancement.

Overcome the problems of conventional dosage forms.Overcome the problems of conventional dosage forms.

LimitationLimitation

The major limitation in the formation of Los is the The major limitation in the formation of Los is the requirement of high purity lecithinsrequirement of high purity lecithins

High purity lecithin is expensiveHigh purity lecithin is expensive

Difficult to obtain in large quantitiesDifficult to obtain in large quantities

Inclusion of pluronics as cosurfectant makes organogelling Inclusion of pluronics as cosurfectant makes organogelling feasible with lecithin of relatively less purityfeasible with lecithin of relatively less purity

ConclusionsConclusions In the last 10 years, there has been an immense growth in research on In the last 10 years, there has been an immense growth in research on

organogels and on publications related to organogels. However, only a organogels and on publications related to organogels. However, only a few organogels have been investigated for drug delivery, mainly due to few organogels have been investigated for drug delivery, mainly due to the fact that the components of most organogels are not pharmaceutically the fact that the components of most organogels are not pharmaceutically acceptable. Thus, before the organogels can be studied as a drug carrier, acceptable. Thus, before the organogels can be studied as a drug carrier, they must be reformulated using pharmaceutically acceptable they must be reformulated using pharmaceutically acceptable components.components.

Of all the organogels studied, MBGs seem to be the most investigated for Of all the organogels studied, MBGs seem to be the most investigated for their application as a matrix where enzymes can be immobilized for their application as a matrix where enzymes can be immobilized for biocatalysis of reactions. While in drug delivery, the potential of MBGs biocatalysis of reactions. While in drug delivery, the potential of MBGs has not been fully explored.has not been fully explored.

Lecithin gels have received more attention as transdermal drug Lecithin gels have received more attention as transdermal drug delivery vehicles, presumably due to the presence of lecithin: a delivery vehicles, presumably due to the presence of lecithin: a known skin permeation enhancer. The promise shown by known skin permeation enhancer. The promise shown by lecithin gels as a transdermal delivery vehicle has resulted in lecithin gels as a transdermal delivery vehicle has resulted in its adoption and adaptation into PLO (which is not an its adoption and adaptation into PLO (which is not an organogel despite the terminology).organogel despite the terminology).

PLO is currently the vehicle of choice of US compounding PLO is currently the vehicle of choice of US compounding pharmacists and veterinarians for the delivery of drugs by the pharmacists and veterinarians for the delivery of drugs by the topical route, despite the lack of any hard, scientific evidence topical route, despite the lack of any hard, scientific evidence of PLO efficacy as a transdermal drug carrier.of PLO efficacy as a transdermal drug carrier.

Apart from the topical/transdermal route, organogels have Apart from the topical/transdermal route, organogels have been also investigated for oral, rectal and parenteral been also investigated for oral, rectal and parenteral applications.applications.

Sorbitan monostearate organogels have shown promise as parenteral Sorbitan monostearate organogels have shown promise as parenteral vaccine adjuvants and as oral vehicles for poorly water-soluble drugs, vaccine adjuvants and as oral vehicles for poorly water-soluble drugs, respectively. Given that many drugs suffer from poor water solubility, respectively. Given that many drugs suffer from poor water solubility, which often leads to low bioavailability, the ability of sorbitan which often leads to low bioavailability, the ability of sorbitan monostearate to solubilise such drugs to increase bioavailability should monostearate to solubilise such drugs to increase bioavailability should be investigated further. be investigated further.

Eudragit organogels are different from ‘classical’ organogels in their Eudragit organogels are different from ‘classical’ organogels in their large, polymeric ‘gelator’, the need for a high gelator concentration, large, polymeric ‘gelator’, the need for a high gelator concentration, were studied > 10 years ago for rectal delivery. Bioavailability of the were studied > 10 years ago for rectal delivery. Bioavailability of the drug from these gels was not higher than from the control formulation drug from these gels was not higher than from the control formulation (Witepsol), and it seems that research into Eudragit organogels for (Witepsol), and it seems that research into Eudragit organogels for rectal delivery has been superseded by research into other, more rectal delivery has been superseded by research into other, more promising formulations.promising formulations.

The alanine derivative gels, in situ forming implants (organogels that form in situ, The alanine derivative gels, in situ forming implants (organogels that form in situ, following the injection of a sol phase) are advantageous over conventional implants in following the injection of a sol phase) are advantageous over conventional implants in that they do not require surgical incision but can be administered by injection, will be that they do not require surgical incision but can be administered by injection, will be interesting as sustained-release depot preparations.interesting as sustained-release depot preparations.

An investigation comparing the different organogels would be of interest to researchers An investigation comparing the different organogels would be of interest to researchers and companies seeking to develop a drug-in-organogel formulation. The few organogels and companies seeking to develop a drug-in-organogel formulation. The few organogels that have been investigated for drug delivery have yielded interesting results, and it is that have been investigated for drug delivery have yielded interesting results, and it is hoped that some of these will make it to the market and improve drug therapy for the hoped that some of these will make it to the market and improve drug therapy for the benefit of patientsbenefit of patients

ReferencesReferences

Murdan S. Organogels in drug delivery, Expert Opinion Drug Delivery, 2(3), 2005, 489-Murdan S. Organogels in drug delivery, Expert Opinion Drug Delivery, 2(3), 2005, 489-505.505.

Anda Vintiloiu, Jean-Christophe Leroux, Organogels and Their Use in Drug Delivery - Anda Vintiloiu, Jean-Christophe Leroux, Organogels and Their Use in Drug Delivery - A Review, Journal of Controlled Release, Accepted 27 September 2007, 18-59.A Review, Journal of Controlled Release, Accepted 27 September 2007, 18-59.

Kumar R and Katare OP. Lecithin organogels as a potential phospholipid-structured Kumar R and Katare OP. Lecithin organogels as a potential phospholipid-structured system for topical drug delivery: a review, AAPS PharmaSciTech, 6(2), 2005, 298-310.system for topical drug delivery: a review, AAPS PharmaSciTech, 6(2), 2005, 298-310.

Murdan S. A review of pluronic lecithin organogel as a topical and transdermal drug Murdan S. A review of pluronic lecithin organogel as a topical and transdermal drug delivery system, Hospital Pharmacist, 12, 2005, 267-270.delivery system, Hospital Pharmacist, 12, 2005, 267-270.

Shchipunov YA. Lecithin organogel: a micellar system with unique properties, Colloids Shchipunov YA. Lecithin organogel: a micellar system with unique properties, Colloids and Surfaces: A Physicochemical and Engineering Aspects, 183-185, 2001, 541-554.and Surfaces: A Physicochemical and Engineering Aspects, 183-185, 2001, 541-554.

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