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ORGANOGEL

Mr. Sagar Kishor Savale[Department of Pharmaceutics]

avengersagar16@gmail.com2015-2016

Department of Pharmacy (Pharmaceutics) | Sagar savale

CONTENTS Introduction

Classification of Organogel

Factors affecting gel formation

Types of Organogel

Applications

Conclusions

References

INTRODUCTION

Gel – Contains both solid & liquid.

Components of gel -Solid -Liquid -Drug. Thermoreversible.

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.

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.

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

Advantages

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• 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.

Organogelators

n-alkanes such as hexadecane & organic liquids

Non ionic surfactant- sorbitan monostearate

Steroids & their derivatives

Anthranyl derivatives

Macrocyclic gelators (calixarenes)

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

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.

Organogel preparationGelators + Liquid phase

HeatOrganic Solution/dispersion

Cool Gel

Why heating and cooling ?

Is this gel form or not ?

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

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

Factors affecting gel formationMolecular 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

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

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

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

L-alanine derivative Organogel

LAM + O.S. + Soyabin oil

Gel Addition of ethanol – Form solution.

(Used as Sustained released implant)

Eudragit Organogel Drug + Polyhydric Alcohol ( PG ) Pour into Eudragit L or S Solution (30 to 40%)

Gelling property – Vary.

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

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

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. 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 deliverypotential

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.

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.

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.

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

Table I: Organogel Formulations Used In Drug Delivery

Sr.No. Types Route ofadministration

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 Sorbitanmonostearate

(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 &DiclofenacMethimazole, Fluoxetine,Dexamethazone, Amitriptyline,Methadone, Morphine,Buprenorphine & BuspironeScopolamine, Metoclopramide,Haloperidol & Prochlorperazine

Sr.No Types Route ofadministration

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

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

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

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

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

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.

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

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

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

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.

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.

THANK YOU !!!

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