Gels Flashcards
What is a gel?
Non-fluid colloidal network or polymer network that is expanded throughout its whole volume by a fluid.
Characteristic of gel
Ability to develop a rigid molecular network (i.e. undergo sol-gel transition) and swell when solvated.
Why do gels swell?
Swelling is due to solvent infiltration into the molecular network, thus unfolding and expanding the molecular network.
How is swelling of gels constrained?
Constrained by intermolecular interactions or cross-links within the molecular network, which confers structural rigidity.
How does the rigidity of gels arise?
A network of colloidal particles or polymer chains.
What does it mean by Gels are viscoelastic semi-solids?
They behave partly like a viscous liquid, partly like an elastic solid.
What are gels semi-solid state described as?
Viscoelastic
What are the two types of gel?
Chemical (type I) and Physical (type II)
What is the polymer network of type I (chemical) gels?
Irreversible polymer network
Why is type I (chemical) gels Irreversible sol-gel transition?
Due to Covalently cross-linked that are not easily broken.
What is the polymer network of type II (physical) gels?
Reversible polymer network
Why is type II (physical) gels reversible sol-gel transition?
The network structure is formed from weak intermolecular bonds and are not permanent.
What is the molecular bonds of type I (chemical) gels?
Covalently cross-linked
What is an example of type I (chemical) gels?
Polyacrylamide gel
What is the molecular bonds of type II (physical) gels?
Weak intermolecular bonds (e.g. H-bonds).
What is an example of type II (physical) gels?
Agarose gel
How do type II (physical) gels undergo sol-gel transition?
In response to specific stimulus (e.g. heat, pH)
Fluid phase of gel type: Hydrogel
Water
Fluid phase of gel type: Alcogel
Alcohol
Fluid phase of gel type: Organogel
Organic solvent
Fluid phase of gel type: Oleogel
Oil
Fluid phase of gel type: Xerogel
None (xero = dry)
Fluid phase of gel type: Aerogel
Air
Fluid phase of gel type: Cyrogel
Produced though freezing (cyro = cold)
Fluid phase of gel type: Hydroalcoholic
Water and Alcohol
Gel type with fluid phase: Water and Alcohol
Hydroalcoholic
Gel type with fluid phase: Water
Hydrogel
Gel type with fluid phase: Alcohol
Alcogel
Gel type with fluid phase: Organic solvent
Organogel
Gel type with fluid phase: Oil
Oleogel
Gel type with fluid phase: None
Xerogel
Gel type with fluid phase: Air
Aerogel
Gel type with fluid phase: Produced though freezing
Cyrogel
What is pharmaceutical gel?
Drug entrapped in gel matrix.
What is the administration for a pharmaceutical gel?
Topical or parental
5 indications for pharmaceutical gel?
Analgesic
Anti-inflammatory
Anti-bacterial
Anti-fungal
Local anaesthetics
Analgesic Gel example
Ibuprofen
Anti-inflammatory Gel example
Diclofenac
Anti-bacterial Gel example
Clindamycin
Anti-fungal Gel example
Miconazole
Local anaesthetics Gel example
Lidocaine
Ibuprofen gel indication
Analgesic
Diclofenac gel indication
Anti-inflammatory
Clindamycin gel indication
Anti-bacterial
Miconazole gel indication
Anti-fungal
Lidocaine gel indication
Local anaesthetics
Dose form retention of gels
The semi-solid structure of the gel makes more likely to be retained at the sight of administration for longer compare to a liquid dosage form.
Environmentally sensitive gels
Conditional drug release triggered by changes in environmental conditions, e.g. pH, temperature.
In-situ gelling systems
- Controlled release: administer in liquid form, drug release in semi-solid form.
- In-situ gelling can be triggered by physiological environment, e.g. body heat.
3 basic components of a gel
Drug
Solvent
Gelling agent
Purpose of solvent in gel
Dissolves drug and excipients, usually aqueous.
Purpose of gelling agent in gel
Forms molecular network, provides structural rigidity, entraps drug.
4 other things a gel may contain?
Cosolvent
pH regulator (buffer)
Preservative
Penetration enhancer
An example of a cosolvent used in gels
Alcohol
Purpose of cosolvent in gel
Enhance drug solubility
Purpose of pH regulator in gel
Enhance solubility of ionisable drugs, avoid skin irritation
Purpose of preservative in gel
Inhibit microbial growth in aqueous gels
Purpose of penetration enhancer in gel
Enhance drug absorption into skin
What usually doubles as a co-solvent and penetration enhancer?
Ethanol
What is Ibuprofen gel used for?
Relief of pain and inflammation associated with backache, rheumatic pain, muscular aches, pains or swellings such as sprains, strains and sports injuries.
Hydroxyethyl cellulose purpose in ibuprofen gel
Gelling agent
Sodium hydroxide purpose in ibuprofen gel
pH regulator
Benzyl alcohol purpose in ibuprofen gel
Antimicrobial preservative
Isopropyl alcohol purpose in ibuprofen gel
Cosolvent and penetration enhancer
Purified water purpose in ibuprofen gel
Fluid component (Exists as a mixture containing other excipients)
What is the sol-gel transition?
The transition of sol to a gel. Gels are formed from sols.
State of sol
Liquid
State of gel
Solid like/semi-solid
2 properties of sol state
- Colloidal dispersion (two or more components) of freely diffusing gelling agent.
- Not a solution (single component).
3 properties of gel state
- Molecules of gelling agent interact covalently or non-covalently, polymer network develops
- Constrained by intermolecular bonds, physical entanglement or cross-links.
- Gelling agent not freely diffusing.
What is the advantage of the sol state?
Work with liquids, measure, mix, and dissolve things evenly.
So prepare then allow it to gel.
When does sol-gel transition happen?
Gel-point, but actually happened gradually over time.
What is the gel point?
Point of incipient polymer network formation
What does the gel point depend on?
The chemical composition of the gel formation
Examples of chemical composition that impact the gel point (5)
– Molecular weight of gelling agent.
– Concentration of gelling agent.
– Concentration of other chemicals (drug, excipients).
– Ionic nature of ingredients.
– H-bonding capacity of ingredients.
What is required for gelation occur?
A minimum concentration of gelling agent is required for gelation—this varies depending on the gelling agent used.
What is the typical gelling agent used in hydrogels?
Polymers that can H-bond with water.
Natural polymers
Cellulose
Gums (e.g. xanthan, tragacanth, carrageenan)
Semi-synthetic polymers
Cellulose derivatives, e.g. methyl cellulose (MC), carboxymethyl cellulose (CMC), hydroxyethyl cellulose (HEC), hydroxypropyl methyl cellulose (HPMC)
Synthetic polymers
Carbomers (Carbopol)
Poloxamers (Pluronic)
What are Cellulosics?
Cellulose polymer and its derivative
How were cellulose derivatives formed?
Side chain altered to tweak polarity. They were substituted with a range of alkyl chains.
What give different physical properties to cellulosics?
Different molecular weights and degrees of substitution
What is the property of high molecular weight gels?
Viscous gels as they can from more extensive networks.
What is the property of low molecular weight gels?
Good film-forming properties. Not as effective as forming gelling agents as they can’t form as extensive networks.
Which cellulosics is anionic?
CMC
Why is CMC anionic?
The COO group (carboxylate)
When can CMC not be used in a formulation?
Drugs that can be ionised under the conditions that exist withing the formulation.
What are carbomers?
Cross-linked polyacrylic acid polymers.
How can gel viscosity and swelling capacity be enhanced when using carbomers?
By neutralisation with a base (e.g. triethanolamine) or by adding hydroxyl donors (e.g. polyols, sugar alcohols) to promote hydrogen bonding.
Dry carbomers
Coiled tightly, not a gel
Hydrated carbomers
ionise (—COO−) and uncoil somewhat due to
electrostatic repulsion between charged groups—low viscosity gel.
Properties of carbomers
Anionic and acidic
What is GelTears eye gel?
Substitution of tear fluid in the management of dry eye conditions.
Carbomer 980 (0.2% w/w) purpose in GelTears eye gel
Gelling agent and Active ingredient
How does Carbomer 980 (0.2% w/w) act as the active ingredient in GelTears eye gel?
Responsible for trapping moisture in the eye
Benzalkonium chloride purpose in GelTears eye gel
Antimicrobial preservative
Water for injection purpose in GelTears eye gel
Fluid component and solvent
Sorbitol purpose in GelTears eye gel
Hydroxyl donor which promotes gel swelling
Sodium hydroxide purpose in GelTears eye gel
Acidity regulator so the gel does not irritate the eye
What usually happens when the gelling concertation is increased?
The more rigid the gel
What is a property of a more rigid the gel?
The slower the drug release
Sol-gel transition temperature of poloxamers depends on…
Chemical composition of the gel formulation
What Chemical compositions of the gel formulation does the sol-gel transitions depend on? (poloxamers)
Poloxamer grade and concentration.
Solvent, drug and excipients.
How can temperature dependence sol-gel transitions help with drug release profile?
The drug release is slowed down when the drug release is close to body temperature, extending its release. (i.e. in gel form)
Poloxamers
Triblock copolymers of polyethylene oxide(PEO) and polypropylene oxide (PPO).
PEO (hydrophilic)
homopolymer of ethylene oxide.
PPO (hydrophobic):
homopolymer of propylene oxide.
Poloxamers properties
Non-ionic, soluble in water, polar and non-polar solvents.
Poloxamer and thermoreversible.
Form thermoreversible gels at 15–50% w/w (depending on specific grades) that are liquid at room temperature, and gel at room/body temperature.
Different physical properties of poloxamer are formed from?
- Different polymer chain lengths (average molecular weight).
- Different ratios of ethylene oxide to propylene oxide.
