DS - Polymers Gels And Surfactants

Question 1

Define disperse systems

Answer 1

What are disperse systems?

Disperse systems consists of particles in one phase (it can be solid, liquid or vapour) dispersed into another phase (again, it can be solid, liquid or vapour).

Often one cannot use the term solubility as one molecule is not dispersed in a liquid for example. Solid, liquids or vapour particles made of numerous molecules will be dispersed in a medium. For them the simple notion of solubility does not apply but rely on a number of forces (attractive and repulsive) as well hydrophobic forces.

One important characteristic is the size range of these dispersed systems.

Question 2

Define polymers, gels and the different gel types

Answer 2

Polymers are macromolecules made of repetitive units (monomer) – poly means many.
Their origin is either natural or synthetic. Natural polymers encompass vegetal, mineral or animal polymers. A typical example are dextrans which are made of units of glucose produced by micro-organisms; dextrans MWs vary from thousands to millions of Daltons.

Gels

• mainly formed by aggregation of colloidal sol particles
• particles link together to form an interlace network, creating a rigid structure
• only a small percentage of disperse phase is required (most have less than 5%w/v
• if liquid is removed from the gel, only the framework remains: this is called xerogel: tragacanth is an example

Slide 15:
Gelation of lyophilic sols (or when the solvent is water, hydrophilic sols). Polymers are often used for these.
There are two types of gels type I or chemical gels, and, type II or physical gels.
Type I or chemical gels: these gels are irreversible as the chains that form the network have been chemically cross-linked. An example are the polyacrylamide gels which are used for DNA sequencing.

Type II or physical gels: these gels are held together by weak intermolecular bonds (Hydrogen bonds) they are often heat reversible (which means that for agarose mentioned before or polyvinyl alcohol gels are obtained when cooling below a certain temperature (temperature called gelation temperature or Tg). Concentrated solution of Pluronic surfactants form gels upon heating as these surfactants have previously formed micelles and these become connected. S

Question 3

Explain their characteristics and which factors affect them

Answer 3

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Question 4

Discuss their use in pharmacy

Answer 4

Polymers (hydrophilic or hydrophobic) are massively used in pharmaceutical science.
They are used in tabletting: polyvinylpyrrolidone (PVP) or povidone as a coating agent, tablet binder or disintegrant. Polyethylene Glycol (PEG) also known as macrogol is used for tablet coating, tablet diluent and lubricant.
Polymers can be used for the controlled release of drugs: in this case they are often used when they form gels or matrices which are loaded with drugs; these are then slowly released (e.g. osmotic pumps or gel patch).
They can be used as excipients for semi-solid preparations (e.g. suppositories) PEG is an example.
Adhesive polymers for skin delivery (gel patch) such as polyacrylate copolymers or polysiloxanes.
Here are another important set of examples of polymers:
- Carboxypolymethylene or carbomer or carbopol: they are used as bioadhesive material; emulsifying agent; emulsion stabilising agent; modified release agent;suspending agent: most of these due to its ability to change the viscosity.
- Cellulose derivatives (methylcellulose, hydroxypropylmethylcellulose or HPMC): hydrophilic polymers
o Methylcellulose is used as coating agent, emulsifying agent, modified release agent, suspending agent, tablet binder and disintegrant, viscosity agent.
o HPMC: capsule shell material, coating agent, dispersant, emulsifying agent, film forming agent solubilising agent etc…
- Natural gums
o Gum Arabic: used as an adhesive and emulsifier;
o Gum Tragacanth: thickener, emulsifier suspending agent.
- PVP: in addition to previously mentioned, it is used as a suspending agent
- PEG: in addition to previously mentioned, it is used as a suspending agent,
as a suppository base or to adjust the viscosity.

Question 5

Define and surfactants and list some of the main surfactants

Answer 5

• surface active agents or surfactants reduce surface tension by moving to an interphase (L/S v/S or L/V)
• facilitate emulsion formation suspensions dispersion, improve wetting or can be used as drug delivery systems
• surfactants have two distinct regions: hydrophobic and hydrophilic thus are amphipathic

There are 4 types of surfactants

Anionic surfactants: these are used in detergents, soaps, as dispersants as wetting agents and as antimicrobials for external application as the charged molecules are not recommended for oral absorption (as they may be toxic).

The example of anionic surfactant you need to keep in mind is Sodium Lauryl Sulfate (SLS) or Sodium Dodecyl Sulfate (SDS) this is the same molecule which is known under these two names. It is represented on the slide. This is a salt (the counter ion being sodium) it is negatively charged and has a long hydrophobic 12 carbon chains.

Non-ionic surfactants: these are commonly used for oral formulations and injections as they tend to have a low toxicity. They are polymer based.
The example of non-ionic surfactant family you need to keep in mind is the polysorbates (PS) also called TweenTM. The most commonly used in formulations are PS20 and PS80; the number 20 and 80 refer to the length of the hydrophobic chains; however, as these are polymers these values 20 and 80 are an average. PS 20 is represented on the slide.

Cationic surfactants: they are used as bactericide as their positively charged head binds to cells, thus destabilises the electrical equilibrium of lipids in the cells which leads to lysis.
The most common one is Cetyl Trimethyl Ammonium Bromide (CTAB) or cetrimide (Cetrimonium bromide). It exists as a salt (bromide is the counter ion) and is represented on the slide.

Zwitterionic surfactants: these are characterised by having both positive and negative charges on the polar head on the surfactant. Drugs such as betaines

Question 6

Explain the formation of micelles, their use and define the critical micelle concentration

Answer 6

There are two types of micelles:

• The (regular) micelle which has the hydrophobic tail of the surfactant inside the micelle and the hydrophilic head of the surfactant on the outside; thus the micelle is formed in an aqueous medium.
• The inverted micelle which has the hydrophobic tail of the surfactant on the outside of the micelle and the hydrophilic head of the surfactant inside the inverted micelle; thus the inverted micelle is formed in an organic medium.

Question 7

Demonstrate awareness of the role of surfactants in pharmaceutical formulations

Answer 7

Pharmaceutical applications
As mentioned previously they can be used to solubilise poorly soluble drugs.
Thy can be used as enhancers of percutaneous absorption: in that case ionic surfactants can enhance transdermal transport.
They are used as flocculating agents in suspensions: they help to create flocs (for example carbopol, veegum or tragacanth)
Mouthwashes contains surfactants which will solubilised debris.
In suppositories, Tween, Myrj, Span increase the absorption rate.
Suspension aerosol and water based aerosols
They are used as emulsifiers (combination of different surfactants as we will see this later).
Solid dosage forms: they are used to wet solids thus facilitate dissolution
They are used in contact lenses cleaning agents, in ear drops to remove cerumen. As mentioned before in therapeutic monoclonal antibodies liquid formulations to limit unfolding of the proteins at the interface.