Gels and Mucilages Flashcards
What are gels and mucilages?
Gels: Transparent or translucent semi-solid preparations that are used for applying active ingredients to the skin and mucous membranes. Generally consist of a liquid phase suspended within a three-dimensional polymer matrix
Mucilages: thick, viscous solutions most commonly produced by dispersing a gum in water
Many agents that form mucilages will also form gels at higher concentrations, or if their solubility is decreased by temperature change
Describe the properties of mucilages. Provide some examples of mucilages.
Mucilages are colloidal dispersions of natural gums eg acacia, tragacanth or semi-synthetic polymers eg methylcelluose
- Mucilages are used as suspending agents in suspensions and viscosity enhancers in oral emulsions. Some act as emulsifying agents for oral emulsions eg acacia, methylcellulose 20. Also can be used as binding agents in tableting
- Mucilages are prone to microbial contamination
- Prone to decomposition – viscosity decreases on storage – usually refrigerated - prepare as required
- APF storage requirements: Refrigerate @ 2-8oC unless otherwise specified, to prevent decomposition
What are some factors affecting viscosity?
> The viscosity of colloids are determined by the shape of macromolecules
- Changes in macromolecule-solvent interaction can lead to the changes in shape
- In “good solvent” linear molecules are extended as the polar group is solvated, resulting in an increase of viscosity
- In “poor solvent”, molecules tend to coil up or fold as intramolecular attraction > macromolecule–solvent affinity
> Ionisable macromolecules are complicated due to charge interaction varying with pH or additives : Max ionisation, polymer stretches out → viscosity increases
> Addition of counter ions (reduces effective charges) molecules contract → viscosity decreases
Describe the properties of acacia (mucilage). What effect does pH and salt concentration have on the viscosity of acacia?
- Acacia is very soluble – up to 37%w/v solutions can be made at 25C
- Hydrophilic colloid - acacia components are high MW polysaccharides
- Emulsifying agent @ 10-20%; suspending agent @ 5-10%
- Too sticky for external use
- Acacia is a polyelectrolyte (lots of COOH groups) – negatively charged due to COO- groups → important properties
- Viscosity highly influenced by pH and presence of salts
Effect of pH and salt concentration on acacia mucilage viscosity
- Decreasing viscosity with increased salt concentration
- Low pH, unionized→low viscosity
- Higher pH, ionized → increased viscosity
- Very High pH, ionized groups shielded by counterions→ low viscosity.
Acacia is a polyelectrolyte, what are some other polyelectrolytes?
- Similar effects observed with other polyelectrolytes (see previous question)
- Tragacanth – initially max viscosity at pH 8, pH 5 after ageing
- Sodium carboxymethylcellulose
- Carbomer – requires neutralization after dispersion to form a gel
How to prepare mucilages?
Colloidal substances that form mucilages and gels are difficult to disperse
> Clumping occurs if mixed directly with water as outside of material forms gel inhibiting further penetration of water
- Using another solvent to “wet” the powder eg glycerol, propylene glycol, ethanol
- Sift the powders slowly into the vortex of a vigorously stirred vehicle
- Use a mechanical blender to achieve intimate mixing
Describe the properties of tragacanth (mucilages)
- Partially soluble in water. Soluble (tragacanthin) and insoluble (bassorin) fractions.
- Insoluble fraction hydrates slowly → viscosity overnight
- Forms highly viscous solution.
- Viscosity is pH-dependent –> best pH 4-7.5
- Used as a suspending agent, viscosity enhancer and gelling agent (5%)
- Reduces efficacy of antimicrobial preservatives at pH 7, but not at pH<5
Describe the properties of methylcellulose (mucilages)
- Identified by numbers indicating the viscosity of 2% solution at 20oC eg Methylcellulose 20
- Soluble in cold water, insoluble in hot water (precipitates at 50-60ºC)
- Large quantities of electrolytes increase viscosity and may cause precipitation of methylcellulose
- Wet with 1/3 hot water (or ethanol or propylene glycol) –> once dispersed, it is dissolved with cold water or ice.
Describe the properties of gels
Gels are semi-rigid systems, consists of a liquid phase (gelling agent) suspended within a three-dimensional polymer matrix. Movement of the vehicle is restricted by the network → increase viscosity = semi-solid.
- May be formed by flocculation of lyophobic solutions or concentrated solutions of lyophilic colloids
- Gels with a high liquid content are described as “jellies”
- Transparent or translucent
- Often aqueous, but can be hydrocarbon-based (hydrogels vs organogels)
- Xerogel –> gel from which the liquid has been removed eg gelatin sheets
Gel properties
- Syneresis: “bleeding” (squeezing out) of the vehicle on storage of gel. Caused by contraction of elastic gel network –> indicative of instability
- Swelling: absorption of liquid by a gel with an increase in volume
- Imbibition: absorption of liquid by a gel without a measurable increase in volume
Rheology (dependent on gel)
- Can be elastic behavior –> like solid
- Can be plastic flow –> solid-like below the yield stress
- Can be pseudoplastic flow –> shear-thinning without yield value
- Thixotropy –> 2 phase gels
What are some advantages and disadvantages of gels?
Advantages of Gels
- High patient acceptability
- Can be applied to mucous membranes
- Easily applied
- Lubricating effect
- High rates of drug release and rapid absorption
Disadvantages of Gels
- Specific preparation methods required
- Some incompatibilities
- Hydrogels require preservation or sterilization
How to classify gels?
According to structure (single-phase vs two-phase):
- Single-phase system: Macromolecules uniformly distributed throughout a liquid. Long flexible chains entangled together by primary or secondary valence forces. No apparent boundaries exist between the two. E.g. tragacanth gel and carboxymethylcellulose gel.
- Two-phase system (thixotropic): gel mass contains a network of small discrete particles (often called magmas) eg bentonite magma
By solubility of the continuous phase (oraganogels and hydrogels)
- Hydrogels are aqueous-based with natural or synthetic hydrophilic polymers eg tragacanth, methylcellulose or colloidal inorganic substances eg bentonite
- Oraganogels use hydrocarbons or animal or vegetable fats as the base eg mineral oil/polyethylene gel –> plastibase
By reversibility of gel formation (type I vs type II)
- Type I (irreversible gels). 3D network of macromolecules joined by covalent bonds. These gels swell when in contact with water but do not dissolve –> used for implants and contact lenses
- Type II (reversible gels). Bonds between molecules are much weaker (van der Waals or hydrogen bonds). Exhibit gel-solid transition with temperature change.
Describe the properties of two-phase gels (magmas)
- Clays –> form gels (referred to as magmas) by flocculation –> card house flocculation of clays eg bentonite
- Crystal structure: flat plate with negative charge on flat side and positive charge on edge
- Thixotropic
Bentonite –> flocculation–> gel –> shaking and break bonds –> solid –> particles collide + flocculation –> gel.
> Bentonite: swells in water to form thixotropic gel, 7-20%, not a clear gel. Used in external preparations (residue is powdery and silky but pH is high (9))
Describe the properties of type I gels
Irreversible gels – insoluble due to covalent links
- Can only swell in the presence of water eg contact lenses, implants, wound dressings
- Absorb large amounts of aqueous fluid; Gel structure is always maintained.
- Strong, but flexible (elastic)
Describe the gelation principles of single-phase hydrogels
- Gels formed from hydrocolloids
- In a mucilage - hydrocolloid macromolecular chains entangle as a result of Brownian motion. The presence of water allows the chains to slip past one another preventing bonding between neighbouring polymers
- If conditions are altered to reduce the hydration of the macromolecular chains, then secondary bonds between neighbouring chains can form → gelation
At sufficient concentration, the viscosity of the dispersion increases to the point of semi-solid. Increased polymer-polymer interactions (Non-Newtonian properties = gel point)
> Higher MW polymers gel at lower concentration
> Electrolytes compete for water → gelation at lower concentration
> Alcohol may cause precipitation or gelation by dehydrating the hydrocolloid
> Methylcellulose and HPC gel at 50-60o
Describe how single-phase hydrogels are produced
Natural gums gel on cooling –> lower solubility (eg gelatin used in jelly)n
- As gel cools, the molecules lose kinetic energy and associate with each other to form long chains. The solvent is trapped in the network and viscosity increases.
Water-soluble polymers eg methylcellulose, gel on heating –> lower solubility
- As the temperature is increased the polymer becomes less soluble (desolvated), lubricant action of solvent is lost, molecules lock together and gel.
- Temperature of gelation = GEL POINT
What are some common gelling agents used in the preparation of single phase hydrogels?
- Tragacanth (natural gum), prepared by dispersing with glycerol and heating with water to form a gel
- Sodium alginate
- Gelatin, prepared by dispersing in hot water and heat to form a gel
- Cellulose derivatives
- Carbomer
- Polyvinyl alcohols
- Poloxamer
What are some other ingredients in gels?
- Humectants – eg Propylene glycol, glycerol to avoid the gel drying out and developing a surface “skin”
- Preservatives – hydrogels can support microbial growth ∴ require compatible preservative.
> Parabens for tragacanth, sodium alginate, NaCMC, hydoxypropyl methylcellulose and carbomer
> Chlorocresol (0.1-0.2%) for alginate gels
> Benzalkonium Chloride (0.01%) for methylcellulose and hydroxypropyl methylcellulose
> Chlorhexidine Acetate (0.02%) for PVA gel
- Therapeutic agents are attached
