Liquid Dosage Forms: Part 1 (Suspensions, Emulsions and Solutions)

Suspension

A coarse dispersion in which insoluble solid particles are dispersed in a liquid medium

What is the Internal phase of a Suspension?

- Consists of insoluble solid particles

- Maintained uniformly throughout the suspending vehicle with the aid of a single or a combination of suspending agents

What is the External phase of a Suspension?

- Suspending medium

- Generally aqueous (water)

- In some instances, it may be an organic or oily liquid for non-oral use.

What are the advantages of Suspensions?

- Hydrophobic drugs

- Patient compliance vs tablets/capsules

- Suspension can improve the chemical stability of certain drugs. (E.g., Procaine penicillin G)

- Drug in suspension exhibits a higher rate of bioavailability than other solid dosage forms

- Suspension can mask the unpleasant/ bitter taste of a drug (E.g., Chloramphenicol)

Bioavailability

The ability and quickness of a drug to be absorbed and used by the body

What is the order of bioavailability within different drug forms?

Solution (Most bioavailable) > Suspension > Capsule > Compressed tablet > Coated tablet (Least bioavailable)

What are the disadvantages of Suspensions?

- A uniform and accurate dose can not be achieved unless suspensions are packed in a unit dosage form

- It is difficult to formulate because they are thermodynamically unstable (maintain their physical form)

- Physical instability and sedimentation can cause problems

What are the desired features of a Suspension?

- Should NOT settle rapidly

- MUST be easily resuspended by the use of a moderate amount of shaking

- Should be easy to pour yet NOT watery and NO grittiness

- Should have a PLEASING odor, color, and palatability

- Should be physically, chemically, and microbiologically stable

- Parenteral/Ophthalmic suspension should be sterilizable

What is the function of a Wetting agent?

*Reduces the surface tension of a liquid by displacing air in the crevices of the particles

- Such liquids are mixed with powders using a mortar and pestle

What are some examples of Wetting agents?

Alcohol, propylene glycol, glycerin, or any other hygroscopic liquid

What is the function of a Suspending agent?

*Viscosity (thickness) inducing agents that are used to reduce the sedimentation rate of particles in a vehicle

What are some examples of Suspending agents?

Agar, Bentonite, Methyl cellulose, Hydroxypropyl cellulose, Carbomer

Polymer

A macromolecule composed of repeating structural units (monomers) typically connected by covalent chemical bonds in a regular or irregular pattern

In this formula, H-(O-CH2-CH2-)n -OH, when n=2, what is the molecular weight?

> Calculate the repeating unit: (O-CH2-CH2-) = C2 + H4 + O1 = 24 + 4 + 16 = 44

> Calculate the front end and back end: H + OH = 1 + 17 = 18

> Multiply 44 by n=2 and add 18: 44 x 2 + 18 = 88 + 18 = 106 g/mol

Surfactants

*Substances that absorb onto surfaces or interfaces to reduce surface tension. May be used as a wetting agent, detergent, or emulsifying agent

What are the 2 important examples of Surfactants?

- Polysorbate 80 (Tween 80)

- Sorbitan monooleate 20 (Span 20)

What are the 2 ways that particles in a liquid stay stable and don't clump together?

- Steric barrier on the surface

- Charge repulsion

Stabilization: Steric barrier on the surface

Polymers with PEG (little hairs) physically block other particles from getting close, so they don't stick together

Stabilization: Charge repulsion

If particles all carry the same electrical charge, they repel each other, keeping them spread out instead of clumping (like magnets with the same pole)

What are the 3 classifications of Suspensions based on application?

- Oral suspension (e.g., Aluminum Hydroxide)

- Externally applied suspension (e.g., lotion)

- Parenteral suspension (e.g., Cholera and Tetanus vaccines)

What are the 2 classifications of Suspensions based on the electrokinetic nature of solid particles?

- Flocculated suspension

- Deflocculated suspension

Flocculation

A process that clumps small suspended particles in a liquid into larger, settleable masses called "flocs"

What are the Mechanisms of "Action" for Flocculating Agents?

> Lowers particle surface charge, resulting in flocs (loose aggregates) (E.g., Electrolytes such as KCl, NaCl, Calcium salts, citrates, phosphate salts)

> Build a gel-like network (polymer with a proper cross-linker)

> Viscosity modifications: Polysaccharides (alginates, starch), water-soluble cellulose, Synthetic polymers

Why might Suspension be thermodynamically unstable?

- Particle size uneven or too small

- Incorrect charges

- Density too high

What are the signs of instability for Suspension?

- Inability to suspend the particles

- Change in color

Pharmaceutical Excipients for Suspension: Excipients for Maintaining the Appearance

> Color

> Preservatives

> Viscosity agents

> Flocculating agents

Pharmaceutical Excipients for Suspension: Excipients for Protecting the active species

> Buffer pH

> Antioxidant

Pharmaceutical Excipients for Suspension: Excipients for Disguising the unpleasant taste/smell

> Sugar

> Flavoring agents

Pharmaceutical Excipients for Suspension: Excipients for Changing the dissolution rates of active species

> Different salt forms

> Different particle size

> Different solvent compositions

Emulsion

One liquid is uniformly dispersed as globules (dispersed) in the other liquid phase (continuous)

The dispersed phase can be stabilised by the presence of a WHAT?

Presence of an Emulsifier

What are the different stages of Emulsions?

*Two phases (oil and water) are agitated together, thermodynamically unstable

- Dispersed system

- Intermediate stage

- Separate bulk phases

Emulsion Composition

Immiscible phases

> Non-aqueous = oil

> Aqueous = water (emulsifier)

What are the types of emulsions used in pharmacy?

- Oral emulsions, injectables, topicals (O/W)

- Topicals, rectals (W/O)

O/W emulsion

> oil-in-water

W/O emulsion

> water-in-oil

What are the forms of Complex/multiple emulsion systems?

- w/o/w

- o/w/o

W/O/W emulsion

> Water-in-oil-in water

> Internal phase = water

> Dispersed phase = oil

> Continuous phase = water

O/W/O emulsion

> Oil-in-water-in-oil

> Internal phase = oil

> Dispersed phase = water

> Continuous phase = oil

W/O/W emulsion has a 3-phase action

1) The outermost water phase ensures an immediate moisturizing of the upper skin layers.

2) In the second phase, the oil droplets merge to form a layer.

3) In the third phase, the innermost water is continually released - in the manner of timed-release capsules - and ensures a long-lasting skin moisturization

What are the basic components of Dermatologic preparations?

- Powder

- Water

- Oil

- Emulsifier

What is the Intention of Use for Dermatologic preparations?

> The majority of these preparations are used for the effects of the therapeutic agents they contain.

> Non-medicated ones are used for physical effects such as protectants or lubricants.