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The word gel is derived from gelatin, and both

gel and jelly can be traced back to the Latin gelu for frost and gelare, meaning freeze or congeal.

This origin indicates the essential idea of a liquid setting to a solid-like material that does not flow, but is elastic and retains some liquid characteristics. The distinction between gel and jelly remains somewhat arbitrary, with some differences based on the field of application. The food industry uses the term gelatin jelly whereas the pharmaceutical industry uses the term gelatin 10/05/13

Gels are defined as semisolid systems consisting

of dispersions made up of either small inorganic particles or large organic molecules enclosing and interpenetrated by a liquid.

Some gel systems are as clear as water in

appearance and others are turbid, since the ingredients involved may not be completely molecularly dispersed (soluble or insoluble) or they may form aggregates, which disperse light.

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The concentration of the gelling agents is mostly

less than 10%, usually in 0.5 to 2.0% range, with

Gels in which the macromolecules are

distributed throughout the liquid in such a manner that no apparent boundaries exist between them and the liquid are called singlephase gels. In instances in which the gel mass consists of floccules of small distinct particles, the gel is classified as a two-phase system and frequently called a magma or a milk. Gels and magmas are considered colloidal dispersions since they each contain particles of colloidal dimension.
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The majority of gels are formed by aggregation of

colloidal sol particles, the solid or semisolid system so formed being interpenetrated by a liquid. The particles link together to form an interlaced network, thereby imparting rigidity to the structure; the continuous phase is held within the meshes. Often only a small percentage of disperse phase is required to impart rigidity, for example 1 % of agar in water produces a firm gel. A gel rich in liquid may be called a jelly; if the liquid is removed and only the gel framework remains this is termed a xerogel. Sheet gelatin, acacia tears and tragacanth flakes are all 10/05/13

Many of the various types of colloidal dispersions

have been given appropriate names. For instance, sol is a general term to designate a dispersion of a solid substance in either a liquid, a solid, or a gaseous dispersion medium. describe the solid-liquid dispersion system. To be more descriptive, a prefix such as hydro- for water (hydrosol) or alco- for alcohol (alcosol) may be employed to indicate the dispersion medium.

However, more often than not it is used to

indicate a dispersion of a solid or a liquid in a gaseous phase. 10/05/13

The term aerosol has similarly been developed to

6

Certain terminology has been developed to

characterize the various degrees of attraction between the phases of a colloidal dispersion. If the disperse phase interacts appreciably with the dispersion medium, it is referred to as being lyophilic, meaning "solvent-loving. If the degree of attraction is small, the colloid is termed lyophobic or "solvent-hating.

lyophobic in alcohol. Terms such as hydrophilic, and hydrophobic, which are more descriptive of the nature of the colloidal property, have therefore been developed to refer to the attraction or lack of attraction of the substance 10/05/13 specifically to water.

For instance, starch is lyophilic in water but

A third type of colloidal sol, termed as association

or amphiphilic colloid, is formed by the grouping or association of molecules that exhibit both lyophilic and lyophobic properties.

Lyophilic colloids are large organic molecules

capable of being solvated or associated with the molecules of the dispersing phase. These substances disperse readily upon addition to the dispersion medium to form colloidal dispersions. As more molecules of the substance are added to the sol, the viscosity is characteristically increased and when the concentration of molecules is sufficiently high, the liquid sol may become a semisolid or solid dispersion, termed a gel.
8

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 Some gels may be come fluid after agitation only to resume

their solid or semisolid state after remaining undisturbed for a period of time, a phenomenon known as thixotrophy. particles. When these are added to the dispersing phase, there is little if any interaction between the two phases. Unlike lyophilic colloids, lyophobic materials do not spontaneously disperse but must be encouraged to do so by special, individualized procedures. affect the viscosity of the vehicle.

Lyophobic colloids are generally composed of inorganic

Their addition to the dispersion medium does not greatly Some substances such as acacia are termed natural colloids

because they are self-dispersing upon addition to the dispersing medium.

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Terminology Related to Gels

A number of terms are commonly used in

discussing some of the characteristics of gels, including imbibition, swelling, syneresis, thixotropy and xero-gel.

Imbibition is the taking up of a certain amount of

liquid without a measurable increase in volume.

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Swelling is the taking up of a liquid by a gel with an increase in volume. Only those liquids that solvate a gel can cause swelling. The swelling of protein gels is influenced by pH and the presence of electrolytes.

10

Syneresis is when the interaction between

particles of the dispersed phase becomes so great that on standing, the dispersing medium is squeezed out in droplets and the gel shrinks. Syneresis is a form of instability in aqueous and non-aqueous gels.

Thixotropy is a reversible gel-sol formation with

no change in volume or temperature. A type of non-Newtonian flow.

A xerogel is formed when the liquid is removed

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from a gel and only the framework remains.

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Gelation of lyophobic sols

Gels may be

flocculated lyophobic sols where the gel can be looked upon as a continuous floccule. Examples are: aluminium hydroxide and magnesium hydroxide gels.

Gel structure, Flocculated lyophobic sol, e.g. aluminium hydroxide.

12

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Clays such as bentonite, aluminium

magnesium silicate (Veegum) and to some extent kaolin form gels by flocculation in a special manner. They are hydrated aluminium (aluminium / magnesium) silicates whose crystal structure is such that they exist as flat plates; the flat part or 'face' of the particle carries a negative charge due to O atoms and the edge of the plate carries a positive charge due to Al 3+/Mg2+ atoms.
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As a result of electrostatic attraction between the face and the edge of different particles a gel structure is built up, forming what is usually known as a 'card house floc'.
Gel structure, 'Card house' floc of clays, e.g. bentonite.

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14

The forces holding the particles together in this

type of gel are relatively weak - van der Waals forces in the secondary minimum flocculation of aluminium hydroxide, electrostatic attraction in the case of the clays - and because of this these gels show the phenomenon of thixotropy, a nonchemical isothermal gel-sol-gel transformation. If a thixotropic gel is sheared (for example by simple shaking) these weak bonds are broken and a lyophobic sol is formed. On standing the particles collide, flocculation occurs and the gel is reformed. Flocculation in gels is the reason for their anomalous rheological properties.
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Gelation of lyophilic sols

Gels formed by lyophilic sols can be divided into

two groups depending on the nature of the bonds between the chains of the network. Gels of type I are irreversible systems with a three-dimensional network formed by covalent bonds between the macromolecules. Typical examples are the swollen networks that have been formed by the polymerization of monomers of water-soluble polymers in the presence of a crosslinking agent. For example, poly (2-hydroxyethylmethacrylate), [poly (HEMA)], crosslinked with ethylene glycol dimethacrylate, [EGDMA], forms a threedimensional structure, that swells in water but cannot dissolve because the crosslinks are stable.
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Such polymers have been used in the

fabrication of expanding implants that imbide body fluids and swell to a predetermined volume. Implanted in the dehydrated state these polymers swell to fill a body cavity or give form to surrounding tissues.

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17

Poly (HEMA):poly (2-hydroxyethyl

methacrylate) cross-linked with ethylene glycol dimethacrylate (EGDMA)

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Type II gels are held together by much weaker

intermolecular bonds such as hydrogen bonds. These gels are heat reversible, a transition from the sol to gel occurring on either heating or cooling.

Poly (vinyl alcohol) solutions, for example, gel on

cooling below a certain temperature referred to as the gel point.

Because of their gelling properties poly (vinyl

alcohol)s are used as jellies for the application of drugs to the skin. On application the gel dries 10/05/13 rapidly, leaving a plastic film with the drug in

19

Concentrated aqueous solutions of high molecular

weight poly(oxyethylene)-poly(oxypropylene)poly(oxyethylene) block copolymers, form gels on heating.

These compounds are amphiphilic, and many form

micelles with a hydrophobic core comprising the poly(oxypropylene) blocks surrounded by a shell of the hydrophilic poly(oxyethylene) chains. Unusually, water is a poorer solvent for these compounds at higher temperatures and consequently warming a solution with a concentration above the critical micelle concentration leads to the formation of more micelles. If the solution is sufficiently concentrated gelation may occur as the micelles pack so closely as to prevent their movement. Gelation is a 10/05/13

20

Amphiphiles, surface-active agents, or surfactants in Gels Certain compounds, because of their chemical structure, have a tendency to accumulate at the boundary between two phases.
Such compounds are termed

amphiphiles, surface-active agents, or surfactants.

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Poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymers. (a) Micelle formation, (b) Formation of a cubic gel phase by packing of micelles.
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Classification of Gels
Gels may be classified into two primary types:

hydrogels, which have an aqueous continuous phase, and organogels, which have an organic solvent as the liquid continuous medium. Gels may also be classified based on the nature of the bonds involved in the three dimensional solid network: chemical gels form when strong covalent bonds hold the network together, and physical gels form when hydrogen bonds and electrostatic and van der Waals interactions maintain the gel network.
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Gelling agents
Gelling agents commonly used are synthetic

macromolecules (e.g., carbomer 934), cellulose derivatives (e.g., carboxymethylcellulose and hydroxypropylmethylcellulose), and natural gums (e.g., tragacanth). water-soluble polymers of acrylic acid cross-linked with allyl ethers of sucrose and/or pentaerythritol. carbomers 910, 934, 934P, 940, 941, and 1342. They are used as gelling agents at concentrations of 0.5 2.0% in water. Carbomer 940 yields the highest viscosity: between 40,000 and 60,000 CP as a 0.5% aqueous dispersion. Depending on their polymeric 10/05/13 composition, different viscosities result. 24

Carbomers in particular are high molecular- weight

The NF contains monographs for six such polymers:

The USP defines gels (sometimes called

jellies) as semisolid systems consisting of either suspensions made up of small inorganic particles, or large organic molecules interpenetrated by a liquid. Where the gel mass consists of a network of small discrete particles, the gel is classified as a two-phase system.

Single-phase gels consist of organic

macromolecules uniformly distributed throughout a liquid in such a manner that no apparent boundaries10/05/13 exist between25the

 A gel mass consisting of floccules of small distinct particles is

termed a two-phase system, often referred to as a magma.

Gels may thicken on standing, forming a thixotrope, and must be

shaken before use to liquefy the gel and enable pouring.

In addition to the gelling agent and water, gels may be formulated

to contain a drug substance, solvents, such as alcohol and/or propylene glycol; antimicrobial preservatives, such as methylparaben and propylparaben or chlorhexidine gloconate; and stabilizers, such as edetate disodium.
Medicated gels may be prepared for administration by various

routes, including the skin, the eye, the nose, the vagina, and the rectum.
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PHYSICAL PROPERTIES OF GELS AND JELLIES

The physical properties of gels and jellies can

be classified into two groups: transitional properties (including gel point, retrogradation, and syneresis) and rheological properties (including rigidity, yield point, and rupture strength). The experimental techniques used to characterize these physical properties can be similarly classified.

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27

Mechanical techniques are used to determine

rheological properties of gels. These techniques employ either small-deformation measurements that yield viscoelastic parameters or large-deformation measurements that generate complete stressstrain profiles, which include failure parameters.

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Gelling concentrations for substances used in pharmaceutical products: Substance GelRequired forming additives concentrati ons (wt %)
Proteins - Collagen - Gelatin Polysaccharides - Agar - Alginates 0.20.4a 215 0.11 0.51 510 (low 0.82

- Pectins a Adjusted to pH > 4 and warmed to 37 C. methyoxy)

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Ca+2 Na+ Ca+2

29

Substance

Gelforming concentrat ions (wt %)

Requir ed additiv es

Semisynthetic polymers (cellulose derivatives) - Carboxymethylcellulose

46 1025 - Hydroxypropylcellulose 8-10 - 2-10 Hydroxypropylmethylcellulo se - Methylcellulose 10/05/13 24

Na+ Na+

30

Substance

Gel-forming Required concentratio additives ns (wt %)

Synthetic polymers - Carbomer - Poloxamer Polyacrylamide - Polyvinyl alcohol

0.52 1550 4 1020

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31

Substance

Gel-forming Required concentrati additives ons (wt %)

35 5 10 4060 Cetrimide

Inorganic substances - Aluminum hydroxide - Bentonite Surfactants - Cetostearyl alcohol - Brij 96b
b

Brij 3099 surfactants are polyoxyethylene-alkyl ethers.

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32

Clearly, gels are semisolids that have both

solid and liquid character under stressthey are viscoelastic substances.

used to prepare lipid-free semisolid dosage forms, including dental, dermatological, nasal, ophthalmic, rectal, and vaginal gels and jellies. Gel vehicles containing therapeutic agents are especially useful for application to mucous membranes and ulcerated or burned tissues because their high water content 10/05/13 33 reduces irritancy.

Gel-forming hydrophilic polymers are typically

Furthermore, these hydrophilic gels are easily

removed by gentle rinsing or natural flushing with body fluids, reducing the propensity for mechanical abrasion. The superior optical clarity of synthetic polymer gels, such as those composed of poloxamer and carbomer, has led to the interest in developing therapeutic ophthalmic gels.

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34

In addition to serving as drug-containing

vehicles, some gels have other important functions. For example, a soft, flexible gel applied to burned skin can prevent excessive water loss by forming a physical barrier. Ocular gel inserts are designed to lubricate the eye continuously and promote healing. Still other gels are intended for lubricating surgical and medical instruments in order to minimize local irritation.
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Many gel-forming substances are available for

preparing pharmaceutical gels and jellies. Although these substances share some common physical characteristics, the intended use may require gelling attributes of a certain substance or blend of substances.

For example, Pharmaceutical Nasal Gels must be: 1. Nasal adherent 2. Odorless 3. Non-irritating 4. Water soluble
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And Pharmaceutical Ophthalmic Gels must be: 1. Optically clear 2. Sterile 3. Mucomimetic 4. Lubricating 5. Demulcent 6. Non-irritating or non-sensitizing 7. Water soluble or miscible
Some simple gel formulations are shown as
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following:

37

Carbomer 941 gel

Carbomer 941 Glycerine Triethanolamine Water Preservative

0.5 (% w/w) 10.0 (% w/w) 0.5 (% w/w) 89.0 (% w/w) q.s.

Procedure: Water, glycerine, and preservative are mixed and the carbomer added by sprinkling on the surface while constantly mixing at high speed. Triethanolamine is added with slow agitation until a clear viscous gel forms. 10/05/13 38

Carbomer 934 alcoholic gel

Carbomer 934 resin 3.0 (% w/w) Glycerine 10.0 (% w/w) Ethanol 40.0 (% w/w) 2-Ethylhexylamine 2.5 (% w/w) Water 44.5 (% w/w)

Procedure: The carbomer is dispersed in the glycerine and water, and a solution of the 2ethylhexylamine in ethanol is added to the water solution with mixing until a clear transparent gel is formed.
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Practical Example on Medicated Gels:

Benzocaine Gel
Benzocaine is a local anesthetic commonly

used as a topical pain reliever. It is the active ingredient in many over-the-counter anesthetic ointments. It is also combined with antipyrine to form Anti-Biotic Otic Drops, to relieve ear pain and remove earwax.
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Benzocaine is used as a key ingredient in numerous pharmaceuticals:

An anti-inflammatory. Over the counter throat lozenges. Some glycerol-based ear medications for use in

removing excess wax as well as relieving ear conditions such as Otitis Media and swimmers ear. Some previous diet products. Some condoms designed to prevent premature ejaculation. Benzocaine acts to desensitize the penis, and theoretically allows an erection to be maintained. Treating pain from mouth and gum irritations (eg, canker sores).
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Before using Benzocaine Gel:

Some medical conditions may interact with Benzocaine Gel. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you: if you are pregnant, planning to become pregnant, or are breast-feeding. if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement. if you have allergies to medicines, foods, or other substances. Because little, if any, of Benzocaine Gel is absorbed into the blood, the risk of it interacting with another medicine is low. 10/05/13 42