INTRODUCTION

A gel is a semisolid preparation of at least two constitutes, consisting of a condensed

mass enclosing and interpenetrated by a liquid. The USP defines that gels are semisolid in
nature. The word gel was coined in 19 th century by Scottish chemist Thomas Graham by clipping
from gelatine.

The process of forming a gel is called gelation. Gelation is promoted by gelling agent. Gelation
can occur either by physical linking or by chemical crosslinking. While the physical gels involve
physical bonds, chemical gelation involves covalent bonds. The first quantitative theories of
chemical gelation were formulated in 1940s by Flory and Stockmayer. Critical percolation
theory was successfully applied to gelation in 1970s. A number of growth models [diffusion
limited aggregation, cluster-cluster aggregation, kinetic gelation] were developed in the 1980s to
describe the kinetic aspects of aggregation and gelation.

QUANTITATIVE APPROACHES TO DETERMINE GELATION:

It is important to be able to predict the onset of gelation, since it is an irreversible process that
dramatically changes the properties of the system.

Average functionality approach- According to the Carothers equation number-average degree of

polymerization DPn is given by

DPn = 2/2-p.fav

Where p is the extent of the reaction and fav is the average functionality of reaction mixture. For
the gel DPn can be considered to be infinite, thus the critical extent of the reaction at the gel point
is found as

pc =2/fav

If p is greater or equal to pc, gelation occurs.

Flory Stockmayer approach- Flory and Stockmayer used a statistical approach to derive an
expression to predict the gel point by calculating when DPn approaches infinite size. The
statistical approach assumes that (1) the reactivity of the functional groups of the same type is the
same and independent of the molecular size and (2) there are no intramolecular reactions
between the functional groups on the same molecule.

Consider the polymerization of bifunctional molecules A-A, B-B, and multifunctionalAf , where
f is the functionality. The extends of the functional groups are pA and pB respectively. The ratio
of all a groups, both reacted and unreacted, that are part of branched units, to the total number of
A groups in the mixture is defined as p. This will lead to the following reaction

A – A + B – B + Af Af-1 – [B – BA – A] n B – BA - Af-1

GEL:

A gel is ranging from soft and weak to hard and tough. It is substantially dilute cross-
linked system, which exhibits no flow when in the steady-state, although the liquid phase may
still diffuse through this system. A gel has been defined phenomenologically as a soft, solid or
solid-like material consisting of two or more components, one of which is a liquid, present in
substantial quantity.

By weight, gels are mostly liquid, yet they behave like solids because of a three-
dimensional cross-linked network within the liquid. It is the crosslinking within the fluid that
gives a gel its structure (hardness) and contributes to the adhesive stick (tack). In this way, gels
are a dispersion of molecules of a liquid within a solid medium.

Gels are become a premier materials used for drug delivery formulations due to its
biocompatibility, network structuring, and molecular stability of the incorporated bioactive
agent.

ADVANTAGES:

• Gels are used to achieve optimal cutaneous and percutaneous drug delivery.
• They can avoid gastrointestinal drug absorption difficulties caused by gastrointestinal pH.
• Gels are having property to avoid enzymatic activity and drug interaction with food and
drinks.
• They can substitute for oral administration of medication when the route is unsuitable.
• They can avoid the first pass effect, that is, the initial pass of drug substance through the
human body.
• They avoid systemic and portal circulation following gastrointestinal absorption.
• Gels are not deactivated by liver enzymes because the liver is bypassed.
• They are non-invasive and have patient compliance.
• They are applied over skin for slow and prolonged absorption.
• Gels have also been applied in pharmacy to some viscous suspension for oral use for
example Aluminium hydroxide gel.
• They have localized effect with minimum side effects.

DISADVANTAGES:

• Gels have possibility of allergenic reactions.

• Enzyme in epidermis may denature the drugs of gels.
• Drugs of larger particle size do not absorb through the skin.
• They have poor permeability of some drugs through the skin.
• Selection of area to be examined carefully during application of gels.
• Gels which are used for the introduction into body cavity or the eyes should be sterilized.
• They may cause application side reactions.
• They may cause skin allergy during application.

IDEAL CHARACTERISTICS OF GELS

Gels should possess the following properties

 Ideally, the gelling agent for pharmaceutical or cosmetic use should be inert, safe, and
should not react with other formulation components.
 The gelling agent included in the preparation should produce a reasonable solid-like
nature during storage that can be easily broken when subjected to shear forces generated
by shaking the bottle, squeezing the tube, or during topical application.
 It should possess suitable anti-microbial activity against microbial attack.
 The topical gel should not be tacky.
 The gels intended for ophthalmic use should be sterile.
CLASSIFICATION:

Classification of Gels is Following:

A. Controlled release gels
B. Organogels
C. Extended release gels
D. Amphiphilic gels
E. Hydrophilic gels
F. Non aqueous gels
G. Bioadhesive gels
H. Thermosensitive sol-gel reversible hydrogels
I. Complexation gels
J. Hydrogel

A. Controlled Release Gels :

Drug delivery to nasal or ocular mucosa for either local or systemic action suffers from
many obstacles. Gel formulations with suitable rheological and mucoadhesive properties
increase the contact time at the site of absorption. However, drug release from the gel must be
sustained if benefits are to be gained from the prolonged contact time.

These gels were formed in simulated tear fluid at concentrations of polymer as low as
0.1%, and it was shown that sodium was the most important gel-promoting ion in vivo.
Rheology, although it may be a questionable technique for evaluating mucoadhesive properties
of polymers, showed that interactions between mucin and polymers were most likely to be seen
with weak gels.
 FIG 1.1: CONTOLLED RELEASED GEL

B. Organogels:

Sorbitanmonostearate, a hydrophobic nonionic surfactant, and numbers of organic

solvents such as hexadecane, isopropyl myristate, and a range of vegetable oils are present.
Gelation is achieved by dissolving/dispersing the organogelator in hot solvent to produce an
organic solution/dispersion, which, on cooling sets to the gel state.

Such organogels are affected by the presence of additives such as the hydrophilic
surfactant, polysorbate 20, which improves gel stability and alters the gel microstructure from a
network of individual tubules to star-shaped "clusters" of tubules in the liquid continuous phase.
Another solid monoester in the sorbitan ester family, sorbitanmonopalmitate, also gels organic
solvents to give opaque, thermoreversible semisolids. Like sorbitanmonostearate gels, the
microstructure of the palmitate gels comprises an interconnected network of rod like tubules.

FIG 1.2: ORGANOGELS

C. Extended Release Gels:

It is a controlled release technology consists of an agglomerated, hydrophilic complex

that, when compressed, forms a controlled-release matrix. It consisting of xanthan and locust
bean gums (two polysaccharides) combined with dextrose surrounds a drug core. In the presence
of water, interactions between the matrix components form a tight gel while the inner core
remains unwetted.

The drug is encapsulated in the pores of the gel, and as the matrix travels through the
patient’s digestive system, the tablet swells and begins to erode. This erosion allows the drug to
“back-diffuse” out through the gel-matrix at a controlled rate until the matrix erodes and a
majority of the drug is released. The fundamental component controlling the rate of release lies
in the properties of the gel matrix.

FIG 1.3: EXTENDED RELEASE GEL

D. Amphiphilic Gels :

Amphiphilic gels can prepared by mixing the solid gelator like sorbitanmonostearate or
sorbitanmonopalmitate and the liquid phase like liquid sorbitan esters or polysorbate and heating
them at 60°C to form a clear isotropic sol phase, and cooling the sol phase to form an opaque
semisolid at room temperature.

Amphiphilic gel microstructures consisted mainly of clusters of tubules of gelator

molecules that had aggregated upon cooling of the sol phase, forming a 3D network throughout
the continuous phase. The gels demonstrated thermoreversibility. Gelation temperature and
viscosity increased with increasing gelator concentration, indicating a more robust gel network.

At temperatures near the skin surface temperature, the gels softened considerably, this
would allow topical application.

FIG 1.4: AMPHIPHILIC GELS

E. Hydrophilic Gels:

Hydrophilic gels are composed of the internal phase made of a polymer producing a
coherent three-dimensional net-like structure, which fixes the liquid vehicle as the external
phase. Intermolecular forces bind the molecules of the solvent to a polymeric net, thus
decreasing the mobility of these molecules and producing a structured system with increased
viscosity.

F. Non Aqueous Gels:

Ethylcellulose was successfully formulated as a nonaqueous gel with propylene glycol
dicaprylate/dicaprate. The novel nonaqueous gel exhibited rheological profiles corresponding to
a physically cross-linked three dimensional gel network, with suitable mechanical characteristics
for use as a vehicle for topical drug delivery. Molecular conformation of the solvent was found
to influence the molecular interactions associated with formation of ethylcellulose gel networks.

The gel matrices exhibited prominent viscoelastic behavior, yield stress and thixotropy.
Rheological and mechanical properties showed significant upward trends with increased
polymeric chain length and polymer concentrations. Good linear correlations were obtained
between rheological and mechanical properties. The solvent molecular conformation was found
to play a role in affecting the formation of gel networks via intermolecular hydrogen bonding
between ethylcellulose polymer chains.
 FIG 1.5: NONAQUEOUS GELS

G. Bioadhesive Gels:

Bioadhesive gels were formulated for nasal delivery of insulin. A nasal perfusion test was
carried out to study the toxicity of four absorption enhancers like saponin, sodium deoxycholate,
ethylenediamine tetra-acetic acid (EDTA) and lecithin.

The gels contained 4000 Iu/dl insulin, 2% or 4% of low and medium molecular weight of
chitosan, and lecithin or EDTA. Drug release was studied by a membraneless diffusion method
and bioadhesion by a modified tensiometry test. The optimized gel was administered nasally in
diabetic rats. The serum insulin levels were analyzed by an insulin enzyme immunoassay kit and
serum glucose by glucose oxidase method kits.

FIG 1.6: BIOADHESIVE GELS

H. Thermosensitive Sol-Gel Reversible Hydrogels:

They are polymeric solutions which undergo reversible sol to gel transformation under
the influence of environmental conditions like temperature and pH which results in insitu
hydrogel formation.
I. Complexation Gels:

The goal of oral insulin delivery devices is to protect the sensitive drug from proteolytic
degradation in the stomach and upper portion of the small intestine.

The insulin remained in the gel and was protected from proteolytic degradation. In the
basic and neutral environments of the intestine, the complexes dissociated which resulted in
rapid gel swelling and insulin release. Within 2 hr of administration of the insulin-containing
polymers, strong dose-dependent hypoglycemic effects were observed in both healthy and
diabetic rats. These effects lasted for up to 8 hr following administration.

J. Hydrogels:

Hydrogels are gel systems in which water immobilised by insoluble polymer. The
elements of hydrogels are water and a polymeric substance that is hydrophilic, but not water
soluble. When exposed to water, the dry polymer swells and absorbs liquid. The polymer strands
are cross-linked either chemically or by physical forces. For convenience, hydrogels may be
defined by the type of polymer employed and/or the cross-linking mechanism.

PROPERTIES

A.Swelling

When a gelling agent is kept in contact with liquid that solvates it, then an appreciable
amount of liquid is taken up by the agent and the volume increases. This process is referred to as
swelling. This phenomenon occurs as the solvent penetrates the matrix. Gel-gel interactions are
replaced by gel solvent interactions. The degree of swelling depends on the number of linkages
between individual molecules of gelling agent and on the strength of these linkages.

B. Syneresis

Many gels often contract spontaneously on standing and exude some fluid medium. This
effect is known as syneresis. The degree to which syneresis occurs, increases as the
concentration of gelling agent decreases. The occurrence of syneresis indicates that the original
gel was thermodynamically unstable. The mechanism of contraction has been related to the
relaxation of elastic stress developed during the setting of the gels. As these stresses are relieved,
the interstitial space available for the solvent is reduced, forcing the liquid out.

C. Ageing

Colloidal systems usually exhibit slow spontaneous aggregation. This process is referred
to as ageing. In gels, ageing results in gradual formation of a denser network of the gelling agent.
In gels, ageing results in gradual formation of a denser network of the gelling agent. Theimer
suggests that this process is similar to the original gelling process and continues after the initial
gelation, since fluid medium is lost from the newly formed gel.

D. Structure

The rigidity of a gel arises from the presence of a network formed by the interlinking of
particles gelling agent. The nature of the particles and the type of force that is responsible for the
linkages, which determines the structure of the network and the properties of gel. The individual
particles of hydrophilic colloid may consist of either spherical or an isometric aggregates of
small molecules, or single macromolecules.

E. Rheology

Solutions of the gelling agents and dispersion of flocculated solid are pseudo plastic i.e.
exhibiting Non Newtonian flow behaviour, characterized by a decrease in viscosity with increase
in shear rate. The tenuous structure of inorganic particles dispersed in water is disrupted by n
gels, ageing results in gradual formation of a denser network of the gelling agent.

CONDITIONS OF GEL FORMATION:

The gel formation is a spontaneous process from a simplepolymer dispersion, or particulate

suspension, and externallyconditions of temperature or solution composition.Thus, the sol-gel
conversion process usually involves aggregation of particles, or macromolecules, with eventual
generation ofa network spanning the entire container volume (Clark, 1992).The formation of gels
can be classified broadly as physically (heat, pressure) and chemically induced (acid,
ionic,enzymatic) gelation reactions. In case of protein gels, the gelation of proteins requires a
driving force to unfold the nativeprotein structure, followed by an aggregation process giving
athree-dimensional organized network of aggregates or strands ofmolecules cross-linked by non-
covalent bonds or less frequently bicovalentbonds. The conditions of gelformation depend
mostly on the several physico-chemical factors as mentioned in the subsequent sections.

Temperature

Heat-induced gelation is probably the most important and common method to obtain gels.
Gelation is a two-step process; an unfolding or dissociation of the molecules due to the energy
input takes placein the beginning to expose reactive sites. The second step isthe association and
aggregation of unfolded molecules to form complexof higher molecular weight. The first step
may be reversible while the second one is usually an irreversible process. Presumably, disulphide
(-S-S-) bridges and hydrophobicinteractions often play major roles. The overall reaction rate
canbe determined either by the unfolding or by the aggregation reaction depending on the ratio
of the reaction rates of the singlesteps in a particular temperature range.

Pressure

High pressure offers an additional degree of freedom in modifying functional properties of

molecules since high pressure canbe applied as a single process or in combination with others,
inparticular with increased temperatures. In general, high pressure favors reactions, which lead to
a reduction of the overallvolume of the system. Pressure causes water to dissociate and the pH
becomes more acidic under pressure. Differences existsin appearance and rheological properties
of gels made with theaof pressure and heat.

Ionic Strength

Monovalent and divalent cations such as sodium and calcium can increase the ionic strength of
the gel. The electrostatic repulsive forces between the molecules are reduced or neutralisedand
agelation can occur. Ionic-induced gelation has been reportedfor pre-denatured whey proteins
and in contrast to heat-inducedgelation, is named cold gelation. Ionic-induced gelation is of
greater importance in polysaccharide gels, for example, alginate, pectin, orcarrageenan.

Ph:

Changes in pH due to the addition of acids or microbial fermentation change the net charge of
the molecule and thereforealter the attractive and repulsive forces between molecules aswell as
the interactions between molecules and solvent, that is,hydration properties. In addition, the
solubility of salts changeswith pH which may contribute to gel formation. The mechanism of
acid gel formation could be explained by the fractalaggregation theory.

Presenceof enzyme:

Enzyme-induced gelation is based on the introduction ofartificial covalent cross-links into food
proteins. Among others,reactions catalyzed by trans-glutaminase (TG), peroxidase,
andpolyphenol oxidase are suitable for cross-linking of proteins.

COMMON INGREDIENTS IN GELS

Ingredients Used in Preparation of Gels are:

A. Antimicrobial preservatives

B. Antioxidant
C. Chelating agents
D. Humectants
E. Fragrances
F. Ideal emulsifier
G. Types of gelling agents
H. Permeation enhancer
I. Co solvent
J. Polymers
K. Colour
L. Adhesives
M. Adsorbents
N. Air displacement agents
O. Alkalizing agents
P. Anticaking agents
Q. Antifoaming agents
R. Antifungal preservative
S. Antistatic agents
T. Bases
U. Binders
V. Buffering agents
W. Flocculating agents
X. Lubricating agents

Mechanism of Drug Absorption:

The principal mechanisms of drug absorption are:
1.Passive diffusion
2.Pore transport
3.Facilitated diffusion
4.Active transport
5.Ionic or electrochemical diffusion
6.Ion-pair transport
7.Endocytosis
 FIG 1.7: MECHANISM OF DRUG ABSORPTION

APPLICATIONS:

 Avoid oral drug degradation

 Extend the product for economical reaonsEg: paint
 Used in gel filteration
 Glycogelation gels are used as a basis for medicated pestilles.
 Formulation of some suppositories Eg. Glycerine suppositories B.P.
 Used in hard and soft gel capsules.
 Gels are used to achieve optimal cutaneous and percutaneous drug delivery.
 They can avoid gastrointestinal drug absorption difficulties caused by gastrointestinal pH.
 Gels are having property to avoid enzymatic activity and drug interaction with food and
drinks.
  They can substitute for oral administration of medication when the route is unsuitable.
 They can avoid the first pass effect, that is, the initial pass of drug substance through the
human body.
 They avoid systemic and portal circulation following gastrointestinal absorption.
 Gels are not deactivated by liver enzymes because the liver is bypassed.
 They are non-invasive and have patient compliance.
 They are applied over skin for slow and prolonged absorption.
 Gels have also been applied in pharmacy to some viscous suspension for oral use for
example Aluminium hydroxide gel.
 They have localized effect with minimum side effects.

REVIEW LITERATURE
1.p.vijaya bhanu et al diclofenac diethanolamine is anon steroidal anti inflammatory drug used in
the treatment of inflammatory degenerative disorder of the musculoskeletal system. The working
and excessive permeability the working hypothesis of the study was that to develop diclofenac
emulgel without isopropyl alcohol and match the invitro and exvivo permeability of optimized
formulation with the conventional formulation. Formulation with dispersion of the drug are also
available in market ,it is also formulated and compressed with marketed formulation.

2.M.Richard Barthele et al non steroidal anti inflammatory drugs have dose related adverse
effects.This system assessed the efficacy and safety of topical diclofenac sodium 1% gel (DSG)
in mild to moderate symptomatic knee osteoarthritis. In a randomized double blind vehicle
controlled trails ,492 adult aged <-with years symptomatic knee osteoarthritis.

3.Enkeleida goa et al the present research has been under taken with the aim to develop a topical
gel of diclofenac sodium 1% evaluation of its physiochemical characteristics and ivitro drug
release through pig skin using vertical diffusion from the study it was concluded that HEC gel
containg diclofenac showed good homogeneity PH value and rhetorical properties with in the
limit allowed for dermatogical preparation HEC diclofenac gel exhibited significantly better drug
release when compared to commercial gel

4.Sugith kumardebarth et al it is non steroidal anti inflammatory drug used in the treatment of
inflammation and degeneration disorder of the musculoskeletal system. It is widely prescribed
for the treatment of osteoarthritis and rheumatoid arthritis .Dysmenorrehea ,acute
lombagesamusculo skeletal trauma and gonorrhea ,acceclofenac is well tolerated with most
adverse event being minor and reversible and effecting mainly GIT most common events include
dysepepesion abdominal pain ,nausea ,ulcerative stomach and pancreasitis.

5.Bindu Nair et al ,Non steroidal anti inflammatory drugs are commonly prescribed for the
medication for the treatment of musculoskeletal disorder osteoarthritis is the most common form
of arthritis in humans and Prevalence rise with age .oral NSAIDS have potential associative
toxicity that must be monitored for and can limit the use of the drugs in certain population
including people of older age.

6. Julie pradal et al , the current study aimed to compare to topical diclofenac products . T he
quantitative evaluation of skin permeability and the qualitative evaluation of their physical
characteristics were perfomed. Diclofenac DEA1.16% emulsion exhibited a statistically
significance higher permeation through human skin at 24 hours through diclofenac sodium 5%
gel when expressed as a percentage of the applied dose of diclofenac through human skin
difference was observed between the diclofenac DEA1.16% emulsion and the diclofenac sodium
gel.

7. N. Sriram et al, in this microsponges were prepared by the double emulsification technique
and subsequently dispersed in a carbopol gel base for controlled delivery of diclofenac sodium to
the skin.
8. Enkulejda goci et al, diclofenac sodium evaluated of its physicochemical characteristics and in
vitro drug release through pig skin using vertical diffusion cell . In the presented work was
evaluated in vitro using abdominal hair less pig skin , into water medium at 37ºc and determined
using spectrophotometer uv at 276nm.

9. Alen G Wade et.al In this comparison between Ibuprofen gel wiyh doclofenac gel and
ibuprofen with levomenthol. Although the gels effectively relieved pain both
ibuprofen/levomenthol and diclofenac gels provided superior global pain relief compared with
ibuprofen gel, with a shorter median time to significant pain relief.

10. H Richard barthel et.al this study assessed the efficacy and safetynof topical diclofnac
sodium 1% gel in mild to moderate symptomatic knee osteoarthiritis, over a 5 month treatment
period, topical treatment with DSG achieved statistically and clinically significant improvement
of pain and measure of physical function.

11. Sujith kumar dibanth et.al, it is non steroidal anti-inflammatory drugused in the treatment of
inflammation and degeneration disorder of the musculoskeletal system. It is widely prescribed
for the treatment of osteoarthritis, rheumatoid arthritis dysmenorreheae, acute lumbago,
musculoskeletal trauma and gonalgia, aceclofenac is well tolerated, with most adverse events
being minor and reversible and effecting mainly GIT most common events includes dysepepsia
abdominal pain , nausea, ulcerative stomach and pancreatitis.

12. Roy altman, diclofenac is a NSAID of phenylacetic acid class with anti-inflammatory
analgesic and anti pyretic properties diclofenac inhibits cyclooxygnase (cox) 2 enzyme with
greater potency than it does cox 1 similar to other NSAIDS diclofenac is associated with
serious dose dependent gastrointestinal, cardiovascular and renal adverse effects it is well
tolerated with most adverse events being minor and reversible inflammatory drug.

13.YS Tanwar et. Al, different gelling agent carbopol NaCMC, HPMC, and sodium alginate in
different concentrations which would attenuated the GIT studies showed the drug release was
decreased with increase in gelling agent concentration. Ethanol was used to dissolve the drug
parabens was used as preservative. It is most effective for treatment like arthritis, pains etc.
sideffects include nausea, pain, irritation etc.

14. D S sandeep the emulgels were prepared with carbopol 934 as a gelling agent used in 6
different concentrations liquid parafen was used as an oil face and methyl and propyl paraben
were included as preservatives. Ethanol was used to dissolve the drug for preparing the aqueous
phase and triethanolamine was addes at the end of preparation.

15. Mohammed razi ullakhan are among the most frequently prescribed drugs. These drugs are
used dermal or systemically in treatment of various rhematic disease including rheumatoid
arthritis as well as for osteoarthritis the present investigation was to develop novel cream
formulation containing diclofnac sodium in combination with more effective and potent natural
anti inflammatory agent

. AIM AND OBJECTIVE

The present investigations was aimed to at the formulation and evaluation of diclofenac sodium
gel to increase the solubility of drug, optimize the concentrations of surfactants with following
objectives:

 To formulate nanoparticulate delivery systems such as drug gel with improved solubility,
it will improve the dissolution rate and permeability which ultimately increase absorption
and hence bioavailability of the poorly water-soluble drugs.
  To evaluate the prepared formulation for in vitro parameters.
 To prove the usage of gel by improving transdermal bioavailability of drugs with poor
water solubility.
 The formulation is optimized by using various surfactants in different ratios.
 To compare the prepared gel with respect to marketed formulation, improvement in
solubility and dissolution rate of in vitro characteristics are found.

PLAN OF WORK:

 Literature survey
 Collection of APIs and excipients
 Preformulation studies-
FT-IR studies of excipients and API
 UV Absorbance studies
 Formulation of diclofenac gel by dispersion method
 Optimization of process and formulation variables for each formulation
 Formulation is characterized by
UV- Spectrophotometric studies
FT-IR studies
Drug content
Invitro drug release
Viscocity

4.DRUG PROFILE:

4.1 DICLOFENAC:

Diclofenac sodium is the sodium salt form of diclofenac, a benzene acetic acid derivative and
non steroidal anti inflammatory drug (NSAID) with analgesic, antipyretic and anti-inflammatory
activity. Diclofenac sodium is a non-selective reversible and competitive inhibitor of
cyclooxygenase(COX), subsequently blocking the conversion of arachidonic acid into
prostaglandin precursors. This leads to an inhibition of the formation of prostaglandins that are
involved in pain, inflammation and fever.
 FIG.4.8 : STRUCTURE OF DICLOFENAC

Molecular Formula: C14H10Cl2NNaO2

Molecular Weight: 296.148 g/mol

IUPAC Name: 2-[2-(2,6-dichloroanilino)phenyl]acetic acid

Proprietary Name: Cambia, Cataflam, Voltaren, Zipsor, Zorvolex

Category: Non steroidal anti inflammatory drugs (NSAID).

PHYSIOCHEMICAL PROPERTIES:

Appearance and Colour: White to off-white crystalline, slightly hygroscopic powder.

Solubility: It is poorly water soluble drug

Partition Coefficient: 1.13-4.75 (pH=7.4)

Melting Point: 279-289°C

Mechanism of Action: As with all NSAIDs, diclofenac exerts its action via inhibition of
prostaglandin synthesis by inhibiting cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-
2) with relative equipotency.

PHARMACOKINETICS:

Absorption: Diclofenac is 100% absorbed after oral administration compared to IV

administration as measured by the urine recovery. However, due to first-pass metabolism , only
about 50% of the absorbed dose is systematically available.
Distribution: The apparent volume of diclofenac sodium is 1.4 L/kg. Diclofenac is more than
99% bound to human serum proteins, primarily to albumin.

Metabolism: The metabolism of diclofenac in humans partitions between acyl glucuronidation

and phenyl hydroxylation, with the former reaction catalyzed primarily by uridine 5’-
diphosphoglucuronosyl transferase 2B7 while the latter is catalyzed by cytochrome P450 and
3A4.

Elimination: The terminal half-life of diclofenac is approximately 2 h, however the apparent

half-life including all metabolites is 25.8-33 h. Diclofenac has a plasma clearance 16 L/h.

USAGE AND ADMINISTRATION: Diclofenac is a medicine that reduces swelling

(inflammation) and pain. It's used to treat aches and pains, as well as problems with joints,
muscles and bones. These include: rheumatoid arthritis and osteoarthritis.

CONTRA INDICATION: diclofenac is now contraindicated in patients with

established: ischaemic heart disease. peripheral arterial disease. cerebrovascular disease.

Adverse Effects: Symptoms of overdose include lethargy, drowsiness, nausea, vomiting, and
epigastric pain, and gastrointestinal bleeding.

Carbopol 934P:

Carbopol 934P is used as a thickener in lotions, creams and gels. It is also used to stabilize,
suspend, and control the release of pharmaceutical products. At low concentrations, suspensions
flow easily with a slippery feel.
 FIG 4.9: CABOPOL 934P

Molecular Formula : (C3H4O2)n

Molecular Weight: 3,000,000

Proprietary Names: Carbopol 941, Polyacrylic acid, Carbomer

Category: Carbomer Homopolymer Type C USP NF

PHYSIOCHEMICAL PROPERTIES:

Appearance and colour: It is a white powder, crosslinked polyacrylic acid powder. It forms
sparkling clear gels or hydro-alcoholic gels and creams.

Solubility: Highly water soluble and polar solvent soluble

Melting point: 116°C

Mechanism of Action: It is used as a thickener in gels, lotions and creams. It is also used to
stabilize, suspend, and control the release of pharmaceutical products.

Uses of carbopol:

 Enhances viscosity of products

 Provide Gel- like Consisitency to fromula

Dispenses Non –Drip Application to products

Increases Thickness of Creams and Lotions

Contraindications: Blurred vision, eyelid margin crusting, corneal irritation, increased

lacrimation; periorbital and conjunctival oedema.
Hydroxypropyl Methyl Cellulose :

HPMC belongs to the group of cellulose ethers in which hydroxyl groups have been substituted
with one or more of the three hydroxyl groups present in the cellulose ring. HPMC is a
hydrophilic, a biodegradable and biocompatible polymer having a wide range of applications in
drug delivery, dyes and paints, cosmetics, adhesives, coatings, agriculture, and textiles. It is also
soluble in polar organic solvents. HPMC possesses increased organo-solubility and thermo-
plasticity compared to other methyl cellulose counterparts. It forms gel upon heating with
gelation temperature of 75-900C.

FIG 4.10: HYDROXYPROPYLMETHYLCELLULOSE

Molecular formula: C56H108O30

Molecular weight: 1261.4 g/mol

Other names: Hypromellose

Melting point: 172°c

Density: 0.25-0.70 g/cm

Physical appearance: White powder

Hydroxypropyl Methyl Cellulose is a non-ionic cellulose ether, in the

appearance of white powder, odorless and tasteless. It is soluble in water, most polar organic
solvents, and the appropriate proportion of ethanol/ water and dichloroethane, but insoluble in
diethyl ether , acetone and anhydrous alcohol. In cold water, it will swell into a clear or slightly
turbid colloidal solution.

Uses of HPMC:

 Cement renders
 Gypsum products
  Pharmaceutical
 Paints and coatings
 Eye drops

Poly Ethylene Glycol:

Polyethylene glycol is a polyether compound derived from petroleum with many applications,
from industrial manufacturing to medicine. PEG is also known as polyethylene oxide (PEO) or
polyoxyethylene (POE), depending on its molecular weight.

FIG 4.11: POLYETHYLENE GLYCOL

Molecular Formula: C2nH4n+2On+1

Molecular Weight: 44.05+18.02 g/mol

Proprietary Names: Polyethylene oxide(PEO), Kollisolv, Carbowax, Macrogol.

Category: Laxative class of drugs

PHYSIOCHEMICAL PROPERTIES:

Appearance and Colour: Colourless, Viscous slightly Hygroscopic liquid.

Solubility: Soluble in water and also soluble in polar solvents such as acetone, alcohols, and
chlorinated solvents. Insoluble in non polar solvents such as hydrocarbons.

Melting Point: -50°C

USES OF PEG:

 The polymer is used as a lubricating coating foe various surfaces in aqueous and non
aqueous environments.
 Since PEG is a flexible, water-soluble polymer, it can be used to create very high
osmotic pressures in gels.

Contraindications: Nausea, gas, bloating and sometimes severe diarrhea.

Methyl Cellulose:
Methylcellulose is a compound derived from cellulose. It is a solid under different trade names
and is used as a thickener and emulsifier in various food and cosmetic products and also a bulk
forming laxative. Like cellulose it is not digestible, non-toxic and not an allergen.

FIG 4.12: METHYLCELLULOSE

Molecular Formula:C20H38O11

Molecular weight:454.5

Proprietary Names: Cellulose, Methyl ether, Methylated cellulose, Methylcellulose

Category: Bulk forming laxative

PHYSIOCHEMICAL PROPERTIES:

Appearance and color: A White, Yellowish-White or greyish-white powder or granules

Solubility: Highly water soluble and practically insoluble in acetone, anhydrous ethanol and in
toluene

Melting point: 290-3050C

Density: 1.01g/cm3

Mechanism of Action: It increases the bulk in the stool, an effect that helps to cause movement
of the intestines. Methyl cellulose absorbs water in the gastrointestinal lumen thereby increasing
the bulk of the stool.

Uses of MethylCellulose:

 It is used to treat constipation and irritable bowel movements

 Helps to maintain regular bowel movements
 Used in the manufacture of capsules in nutritional supplements

Contraindications: Blockage of the esophagus, Appendicitis, Blockage of the stomach and

intestine, Difficulty swallowing
Tween-80:

Tween 80 is a nonionic surfactant and emulsifier often used in pharmaceuticals, foods, and
cosmetics. This synthetic compound is a viscous, water soluble yellow liquid.

FIG 4.13: TWEEN-80

Molecular formula: C64H124O26

Molecular weight: 1,310 g/mol

Other names: Polysorbate 80, Kolliphor PS 80, Montanox 80, Alkest TW 80, Kotilen 80

Category: Non-ionic surfactant

PHYSIOCHEMICAL PROPERTIES:

Appearance and color: Amber colored viscous liquid

Solubility: Tween 80 is miscible in water and yields a clear, yellow solution. It is also miscible
with alcohol, dioxane, and ethyl acetate and is practically insoluble in liquid paraffin and fixed
oils.

Melting point: -250C

Density: 1.102 g/ml

Mechanism of Action: A solubilizing agent acts as a surfactant and increases the solubility of
one agent in another. In food or pharmaceutical products, it can act as an emulsifier.

Uses of Tween 80:

  Tween 80 is used as emulsifier in foods
 Used as surfactants in soap and cosmetics
 Used as surfactant and solubilizer in variety of oral and topical pharmaceutical products.
 It is used as antimicrobial preservative and disinfectant.

Contraindications: Slight skin irritation, Eye irritation, Irritation of the nose, throat, and
respiratory tract.