ORGANOGEL CONTROLLED RELEASE FORMULATION: A NOVEL …

www.wjpps.com │ Vol 10, Issue 9, 2021. │ ISO 9001:2015 Certified Journal │

1821

Khan et al. World Journal of Pharmacy and Pharmaceutical Sciences

ORGANOGEL CONTROLLED RELEASE FORMULATION: A NOVEL

APPROACH

Fayza Khan*, Rahul Maurya and Suman Ramteke

School of Pharmaceutical Science, RGPV, Airport Bypass Road, Gandhi Nagar,

Bhopal, Madhya Pradesh.

ABSTRACT

Background: Over the years, attentiveness in organogel has developed

speedily with numerous inventions and synthesis of different

molecules that can gel organic solvents at less concentration. Main

Body of the abstract: Organogel are hydrophilic and lipophilic drug

delivery system either topically or transdermally therefore, they are site

specific drug delivery systems. They are thermodynamically stable,

biocompatible with skin and are simple to prepare with few

components. Organogel provide enhanced drug penetration and

absorption across the skin due to their desired drug portioning and

biphasic drug solubility. Short conclusion: The current review reflects

the overview of organogel following in briefs about gels that have been instigated in drug

delivery system this will enhance research of organogels and suggest upcoming prospective

of organogel for its uses.

KEYWORDS: Organogel, Permeation, Organogelator, Topical drug delivery.

1. Background section

From conventional dosage forms like tablets, capsules, parental, rectal, vaginal. There were

many drawbacks but over the decade the development of novel drug delivery system.

Gel are both liquids and solids containing formulation, which comparatively semi solid in

nature. in which as solid component exist gelator as a network of clusters, which holds the

liquid component.(Sahoo et al. 2011),(Mehta, Bhatt, and Kothiyal 2016).

WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

SJIF Impact Factor 7.632

Volume 10, Issue 9, 1821-1833 Review Article ISSN 2278 – 4357

*Corresponding Author

Fayza Khan

School of Pharmaceutical

Science, RGPV, Airport

Bypass Road, Gandhi Nagar

Bhopal, Madhya Pradesh.

Article Received on

15 July 2021,

Revised on 05 August 2021,

Accepted on 25 August 2021

DOI: 10.20959/wjpps20219-19975


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1.1 Main body

Organogels are thermodynamically steady, viscoelastic, biphasic in nature, biocompatible

systems, containing a gelator and nonpolar solvent, may include water within the network

setup by gelling agent.(Patel et al. 2018) They have the ability to act as template and to

control the release rate of drugs.(Anand et al. 2001).

1.2 Importance of organogels

For topical drug delivery of drug at site specific, many methods are inspected. From the

available topical applications systems, gels are more used due to their convenience of use and

better absorption through topical route. Organogel have proven to a novel system for use, as

they can be used for both lipophilic and hydrophilic drug delivery.

1.3 Properties of organogel

Table no. 1: Factors affecting Organogel and Their role.

S. no. Factors affecting

organogel Description of parameters

1

Organic solvent

Polar solvent

Non-aqueous

solvent

The use of polar solvent in lecithin micelles can increase the

cross section area of lecithin polar area during solvent

arrangement.(Smith et al. n.d.)

Polyethylene glycol, dimethyl ether can also be used as

solvent other than non-aqueous solvent can be used till it can

replaces water of the bacterial cellulose hydrogel completely

without changing its shape.(Baran et al. 2014)

2 Phase Transition

Temperature

A narrow PTT range can show a homogenous microstructure

which is within the gel. It can give a perception of nature of

microstructures that form gelling cross-linked network.(Shah

et al. 2013),(Ibrahim et al. 2013)

3 Salt addition

Salt out is when the part of water of hydration attracts the

polymer allow more formation of inter molecular secondary

bonds.(Organogel, Gel, and Solvent 1991)

4 Temperature

Its effect depend on the polymer mechanism of interaction

and its chemistry with solvent.(Martinez 2019) If the

temperature is lowered once the gel is within the solution the

degree of hydration will be less and gelation will occurs. The

resulting gel formed by the cross linking of

chemicals.(Gowdhaman et al. 2015),(Motulsky et al. 2005)

5 Molecular weight

High concentration of Low molecular weight polymers is

needed to make up the viscosity and to set gel as required.

(Ibrahim et al. 2013)

6 Surfactants

Gel characteristics can be varied by changing the ratio and

concentration of the ingredients. Pluronic F127 is poly-oxy-

ethylene that works as a surfactant.(Bhatia et al. 2013)


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7

Physicochemical

properties

Charge

Solubility

Molecular

weight

Muco-adhesion take place due to the presence of charged

groups. Poly-anions and poly-carboxylates are favourable

then poly-cations.

When Muco-adhesives comes in contact with moisture they

increases the polymer mobility at the interface and thereby,

revealing more sites for the formation of bonds.(Mady et al.

2016),(W. Liu et al. 2016)

Polymer and Mucin interaction interpenetrate and favours

the change in entanglement and interaction.

2. Organogelators: They are the material when added to an organic solvent forms an

organogel like: (Lv et al. 2017)

n-alkanes & organic solvents

Non- ionic surfactant

Steroids & its derivatives

Anthranyl derivates

Macrocyclic

2.1 Organogel Structure & Mechanism of organogelling: (Organogel as a Drug Delivery

System n.d.)

The organogelling of lecithin in organic phase is induced as a result of introduction of a water

phase.

When lecithin is dissolved in oil phase separately, it itself assembles into reverse micelles.

The extension of spherical reverse micelles & their transformation into tubular & cylindrical

micelle cluster which is initiated by addition of minute amounts of polar additives.

2.2 Classification of organogelators: (Vintiloiu et al. 2008),(Alsaab et al. 2016)

Fig. 1: Organogelators types.


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2.3 Methods of preparation of organogel (Agrawal et al. 2010)

2.3.1 Fluid-filled fiber method

Apolar Solvent + Surfactant/Co-surfactant mixture

Reverse micelles

Tubular reverse micelles

Elongated tubular reverse micelles gets entangled to form a 3-D network, which immobilizes

apolar solvent.

2.3.2. Hydration method

In this method Gel are prepared by directly hydrating the inorganic chemical resulting in

dispersion. Introduction of water vehicle and other agents which can enhance gel formation.

(Sangale et al. 2015)

2.3.3 Solid fiber method

Fig. 2: Method of preparations of organogels by solid fiber mechanism.

2.3.3. Novel method (Gökçe et al. 2013)

i. Homogenisation method


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ii. Micro irradiation method

3. Absorption through Skin and Routes of skin permeation

3.1 Route of skin permeation: Absorption of drug across the skin can be elucidate as

permeation of drug molecules through skin into systemic circulation. (Mehta et al. 2016)

The different routes of topical permeation are enlisted in table no. 3. (Brown et al.

2006),(Leppert et al. 2018)

Table no. 2: Route of permeation.

Penetration Permeation Absorption

It involves the

movement of a

molecule inside a

layer of skin.(Marwah

et al. 2016)

It involves the

movement of a molecule

from one layer of skin

into another.(Simsolo et

al. 2018)

It involves the transfer a

molecule from skin into

the systemic circulation.

(Pénzes et al. 2005)

3.2 Route of skin permeation: (Benson et al. 2019),(Kumar and Katare 2005)

The routes through which molecules permeate through the skin can be classified as:

Intercellular diffusion through the lipid lamellae.

Transcellular through the keratinocytes an lipid lamellae. (Patel et al. 2018)

Diffusion through appendages like the hair follicles and sweat glands.

Fig. 3: Drug permeation pathway.


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4. Common types of organogel

1. Lecithin organogel: Lecithin organogels thermo-dynamically inert, visco-elastic, bio-

compatible. They are made up of lecithin and a polar solvent.(Avramiotis et al.

2007),(Jadhav et al. 2009)

2. Pluronic lecithin organogel: These are lecithin based organogels are broadly used as a

medium for enhancing permeability though the skin for many drugs. (Jatav et. al

2015),(Pandey et al. 2010)

3. Premium lecithin organogel: These are also called 2nd generation lecithin Organogel.

They have more thermo stability, have non-oily and non-sticky property, due to this they

are widely use cosmetically.

4. Limonene GP1/PG Organol: It is a hydrocarbon, work as outstanding penetration

enhancer therefore it is use in organogel containing gelator GP1 and PG. it can be used

transdermal patch due to its good skin compatibility. They are long-acting formulation

and can be used for delivery of drug at sustained percutaneous rate.(Sahoo et al.

2011),(Esposito et. al 2018)

5. Gelatine-Stabilized Micro-Emulsion-Based Organogel: MBG gelatin can be use as

protein for several food as structural agent. Formulations containing excess of aqueous

phase.(Kumar et al. 2005),(Trickett et al. 2010)

6. Fatty-Acid-Derived sorbitan organogels: Sorbitan monostearate as well as sorbitan

mono palmitate use as gelator. They are lipophilic non-ionic molecule with surface-active

property, which can immobilize several solvents, like, isopropyl myristate and vegetable

oils. A solid-fiber matrix is formed by gelators in apolar solvent, when cool down from its

transition temperature. The configuration of gel has been achieved by reverse micelle’s

formation as, the temperature is decreased. The gels formed from using these gelators are

cloudy in appearance, thermo-reversible and are Heat-stable at room-temperature for

days.(Meng et al. 2019), (Rustan 2005)

7. Polyethylene organogels: They are uncoloured, odourless preparations. These

formulations are produced by maintaining the temperature of mineral oil at >130◦C and

adding low molecular weight polyethylene into it, this blend kept until it cools down.

Polyethylene organogels are commonly implemented for the preparations of base in

different formulation of ointments. The reason behind the gelation or formation gelled

network is an account of solid-fibers interaction with polyethylene.(Meng et al. 2019)


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5. Different organogel formulation applied for various drug deliveries and their route

of administration

Table no. 3: Organogel formulations used in drug Delivery and Their route of

administration.

Organogel Composition Route of

administration

Activity Model drug Ref.

Lecithin

organogels

Oil 20%

Water 80%

Transdermal Treatment of

Arthritis,

Antifungal

Lornoxicam

Fluconazole

(Raut et al.

2012)

Pluronic

lecithin

organogel

Oil 30%

Water 70%

Transdermal Antinociceptive

, NSAID

Sumatriptan,

Flurbiprofen,

Dexamethasone

(MAYRA

2013),(Pandey

et al. 2010)

Premium

lecithin

organogel

- Intradermal Anti-fungal,

dysphoric

disorder,

NSAID,

Amphotericin

B,

Progesterone,

Diclofenac.

(PLO Gel

Premium

Lecithin

Organogel

Base

Transdermal:

Uses, Side

Effects,

Interactions,

Pictures,

Warnings &

Dosing -

WebMD n.d.)

Limonene

GP1/PG

Organogel

GP1 10%

GP 90%

Transdermal Anti-psychotic Haloperidol (HARUSAW

A

1986),(Fung

et al. 2006)

Gelatin-

Stabilized

Microemulsi

on-Based

Organogel

(MBG)

25% w/w

surfactant,

25% w/w

water and

50% w/w IPM

percutaneous,

cutaneous,

transdermal

Antimicrobial,

NSAID,

Metronidazole,

Piroxicam,

Propranolol

hydrochloride,

ketorolac

tromethamine

(H. Liu et al.

2007),(Ojeda-

Serna et al.

2019)

Fatty-Acid-

Derived

Sorbitan

Organogels

SMP 20%

CO 80%

Nasal, Oral,

Subcutaneous &

intramuscular

Treatment of

Alzheimer’s,

Antimicrobial,

Anticancer,

Analgesic

Rivastigmine,

Metronidazole,

Cyclosporin,

Ibuprofen,

Aspirin,

Paracetamol

(Pénzes et al.

2005),(Angeli

co et al.

2005), (Singh

et al. 2015)

Polyethylene

Organogels

LMW

polyethylene,

mineral oil

Transdermal Hormone

therapy

Leuprolide

(Zou et al.

2013),


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Organogels

based on

other low

molecular

weight

gelators

Methyl (S)-

2,5-

ditetradecana

midopentanoa

te &

Soyabean oil

(any oil)

Cutaneous Anti-psychotic

Haloperidol

(Motulsky et

al.

2005),(Giuri

et al. 2019)

Supramolecu

lar

organogels

- Topical,

injectable

lubricant, Anti-

inflammatory

Lithium 11-

hydroxystearate

, imidazolium

(Rings 2019)

Eudragit

organogels

Eudragit 30%

Polyhydric

alcohol 40%

Buccal

Rectal

NSAID, Ketoprofen,

Salicylic acid,

Sodium

salicylate

(Kim

1991),(Kim

and Kurita

1990)

In situ

forming

organogel of

L-alanine

derivative

N-lauryl-L-

alanine

methyl ester

(LAM),

organic

solvent &

soyabean oil

Subcutaneous Hydrophobic

implant

Fluorescein

isothiocyanate

dextran

(Motulsky et

al.

2004),(Motuls

ky et al. 2005)

CONCLUSIONS

Organogel increases the shelf life, thermodynamic stability, efficacy and feasibility of the

drug that incorporated in them. There are different types of organogel use as the drug carrier

in which various types of drugs can be suspended inside the organogel for local as well as

systemic effect of different therapeutics. It is economical and productive formulation which

can become a milestone in the field of topical drug delivery. As organogel provide better

penetration this can be used in the treatment of topical diseases and for site specific drug

delivery like fungal infection, microbial infection, antibiotic arthritis, antihypertensive, skin

cancer, migraine, skin rashes, etc. use as site specific NSAID action.

List of abbreviations

NSAID: Non-steroidal anti-inflammatory drug

C: Celsius MGB: Micro-emulsion gelatin based organogel

PTT: Phase transition temperature

GP1: Di-butyllauroylglutamide

PG: Propylene glycol

LAM: L-alanine methyl

LMW: Low molecular weight


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SMP: Sorbitan monopalmitate

CO: Castor oil

IPM: Isopropyl myristate

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