Lecture 20: Gels Flashcards
What is a gel?
- Non-fluid colloidal network or polymer network that is expanded throughout its whole volume by fluid
What is the characteristic of gel?
- Ability to develop a rigid molecular network
- Undergo sol-gel transition and swell when solvated
Why do gels swell and what is it constrained by?
- Due to solvent infiltration into the molecular network, thus unfolding and expanding its molecular network
- This is constrained by intermolecular interactions or cross links within the molecular network - 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?
- Behave partly like a viscous liquid
- Partly like an elastic solid
- Halfway between liquid and solid
What are the 2 types of gels?
- Chemical (Type 1)
- Physical (Type 2)
What is the polymer network of type 1 (chemical) gels like?
- Irreversible polymer network
- Covalent bonds are very strong and not easily broken
What is the polymer network of type 2 (physical) gels?
- Reversible polymer network
- Start as liquid then semi-solid than liquefy again
- Electrostatic or H-bonding (weak intermolecular bonds & not permanent)
What is an example of type 1 (chemical) gel and type 2 (physical) gel?
- Polyacrylamide gel
- Agarose gel
How do type 2 (physical) gels undergo sol-gel transition?
- In response to stimulus e.g. heat, pH
What is the fluid phase of gel type: hydrogel, alcogel and organogel and hydroalcoholic?
- Water
- Alcohol
- Organic solvent
- Water and alcohol
What is the fluid phase of gel type: oleogel, Xerogel, Aerogel, cryogel?
- Oil
- None (xero = dry)
- Air
- Produced through freezing (cryo = cold)
What is a pharmaceutical gel and its administration?
- Drug entrapped in gel matrix
- Topical or parental
What are 5 indications for pharmaceutical gel and an example?
- Analgesic (ibuprofen)
- Anti-inflammatory (diclofenac)
- Anti-bacterial (Clindamycin)
- Antifungal (Miconazole)
- Local anasthetics (lidocaine)
What is dose form retention of gels?
- The semi-solid structure of the gel makes more likely to be retained at the site of admin for longer than liquid dosage
What are environmentally sensitive gels?
- Conditional drug release triggered by changes in environmental conditions e.g pH temperature
What are 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
What are the 3 basic components of a gel and what is the purpose of the solvent and gelling agent?
- Drug
- solvent: dissolves drug and excipients, usually aqueous
- Gelling agent: forms molecular network, provides structural rigidity, entraps drug
What are 4 other things a gel may contain and what are the purposes of each?
- Co-solvent: enhance drug solubility
- pH regulator (buffer): enhance solubility of ionisable drugs, avoid skin irritation
- Preservative: inhibit microbial growth in aqueous gels (important for multiple use)
- Penetration enhancer: enhance drug absorption into skin
What is an example of a co-solvent used in gels?
- Alcohol
What usually doubles as a co-solvent and penetration enhancer?
- Ethanol
What is Ibuprofen gel used for?
- Relief of pain and inflammation with backache, rhematic pain, muscular ache
- Or pain/swelling from sprains and injuries
What is the purpose of hydroxyethyl cellulose in ibuprofen gel?
- Gelling agent
- It is a polymer and only polymer
What is the purpose of the sodium hydroxide, benzyl alcohol, isopropyl alcohol and purified water in the ibuprofen gel?
- pH regulator
- Antimicrobial preservative
- Cosolvent and penetration enhancer
- Solvent
What is the sol-gel transition?
- The sol-gel transition is the process where a material changes from a sol (solution or colloidal suspension/liquid) into a gel (semi-solid network).
What are 2 properties of the sol state?
- Colloidal dispersion (2 or more components) of freely diffusing gelling agent
- Not a solution (single component)
What are 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 happens gradually over time
- This is the point of incipient (begin) polymer network formation
- This depends on the chemical composition of the gel formation
What are 5 chemical compositions that impact the gel point?
- 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 to occur?
- A minimum concentration of gelling agent is required
- Varies depending on gelling agent used
What is the typical gelling agent used in hydrogels?
- Polymers that can H-bond with water
Name some natural polymers?
- Cellulose
- Gums (e.g xanthan, tragacanth, carrageenan)
Name some semi-synthetic polymers?
- Cellulose derivatives (methyl cellulose MC, carboxymethyl cellulose CMC, hydroxyethyl cellulose HEC, hydroxypropyl methyl cellulose HPMC)
Name some synthetic polymers/
- Carbomers (Carbopol)
- Poloxamers (Pluronic)
What are cellulosics and what gives them different physical properties?
- Cellulose polymer and its derivative
- Different molecular weights and degrees of substitution
How were cellulose derivatives formed?
- Side chain altered to tweak polarity
- They were substituted with a range of alkyl chains
What is the property of high molecular weight gels and low molecular weight gels?
- Viscous gels as they can form extensive networks
- Good film forming properties, not as effective as forming gelling agents as they cant form extensive networks
Which cellulosics are anionic and why?
- CMC
- The COO group carboxylate
What are carbomers and their properties?
- Cross linked polyacrylic acid polymers
- Anionic and acidic
How can gel viscosity and swelling capacity be enhanced when using carbomers?
By neutralisation with a base (e.g. triethanolamine) or by adding hydroxy donors (e.g. polyols, sugar alcohols) to promote hydrogen bonding
What are dry carbomers and hydrated carbomers?
- Coiled tightly, not a gel
- Ionise (-COO) and uncoil somewhat due to electrostatic repulsion between charged groups - low viscosity gel
What is GelTears eye gel and what is the purpose of Carbomer 980 (0.2 w/w) in the eye gel?
- Substitution of tear fluid in the management of dry eye conditions
- Gelling agent and active ingredient (it traps moisture in the eye)
What is the purpose of the benzalkonium chloride, sorbitol and sodium hydroxide purpose in GelTears eye gel?
- Antimicrobial preservative
- Hydroxyl donor which promotes gel swelling
- Acidity regulator so the gel doesnt irritate the eye
What usually happens when the gelling concentration is increased?
- The more rigid the gel and slower drug release
What does the sol-gel transition temperature of poloxamers depends on?
- Chemical composition of the gel formulation
What are poloxamers?
- Type of synthetic, biocompatible polymer used in pharmaceutical applications
- Thermo-responsive behavior, meaning it can transition from a liquid to a gel with temperature changes
- Poloxamers are triblock copolymers composed of:
Poly(ethylene oxide) (PEO) hydrophilic (water-attracting),
Poly(propylene oxide) (PPO) – hydrophobic (water-repelling), Poly(ethylene oxide) (PEO) again
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 drug release is close to body temperature, extending its release (i.e. in gel form)
What are poloxamer properties?
- Non-ionic soluble in water, polar and non-polar solvents
What is a key characteristic of poloxamers, particularly Poloxamer 407, in drug delivery systems
- Form thermo reversible gels at 15-50%w/w (depending on specific grades) that are liquid at room temp, and gel at room/body temp
What are different physical properties of poloxamer are formed form?
- Different polymer chain lengths (average molecular weight)
- Different ratios of ethylene oxide to propylene oxide
