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PMP-102 > Emulsion Dosage Forms > Flashcards

Emulsion Dosage Forms Flashcards

1
Q

Everyday emulsions:

A
  • Serum
  • Cheese/ butter
  • Paint
  • Wet chemicals/fire distinguisher
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2
Q

Pharmaceutical emulsions/ applications:

A
  • Topical delivery = creams
  • Total parenteral nutrition (intravenous feeding of fat emulsions)
  • Oral delivery and taste masking (cod liver oil)
  • As vehicle for drug (emulsions containing propofol)
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3
Q

Emulsions - what is it?

A

A ‘pseudo-stable’ dispersion of at least two immiscible liquids, one of which is dispersed throughout the other in the form of fine droplets (generally oil and water) stabilised by the presence of an emulsifying agent (known as emulsifier)

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4
Q

Oil in water / Water in oil

A

Emulsified oil droplet by WATER

Water droplets emulsified by OIL

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5
Q

Which one is easily spreadable

A

Water in oil (w/o)

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6
Q

Which one is easily rinsed off of skin?

A

Oil in water (o/w)

e.g. milk is easier to rince off rather than sun cream

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7
Q

o/w = which is the bulk phase?

A

Water

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8
Q

Properties of emulsions:

A

Cloudy or milky

Droplet sizes are polydispersed (nm to µm)

Low concentration of surfactant/cosurfactant

Thermodynamically unstable but kinetically stable(feasible to separate, but happens very slowly)

Prepared by input of large amount of energy, e.g. high speed homogenisation, sonication, heat

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9
Q

Emulsion types

A

Normal emulsion (o/w)

Reverse emulsion (w/o)

Multiple emulsion (o/w/o or w/o/w)

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10
Q

Emulsion examples

A

o/w emulsions
Vehicles for lipophilic drugs

w/o emulsions
Sunscreen

w/o/w emulsions
Vancomycin hydrochloride – enhanced enteral bioavailability

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11
Q

Creams

A

Semi-solid emulsions of two immiscible phases stabilised by emulsifying agent (either o/w or w/o)

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12
Q

o/w ‘watery’ creams

A

Water is the continuous medium, while oil is the dispersed phase, therefore o/w creams do not feel greasy

Can deposit lipids so restore skin hydration, however they are non-occlusive

Rub into the skin, leaving behind a thin film of rapidly releasing water-soluble drug

Readily diluted and miscible with water; easily rinsed off

Conduct electricity
Prepared using surfactants with higher HLB (8-16)

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13
Q

w/o ‘oily’ creams

A

Are more greasy, since oil is the continuous phase

More moisturising as they provide an oily barrier which reduces water loss from the outer layer of the skin

Hydrophobic drugs are better formulated and
more readily released

Miscible with oil therefore not easily washable, however more easily spreadable

Do not conduct electricity

Prepared using low HLB surfactants (3.5-8)

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14
Q

Creams are a type of…

A

Surfactant used determines the type of cream prepared (o/w or w/o)

     >Important to consider the HLB of the surfactant mixture
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15
Q

Semi-solid creams require excess surfactant/co-surfactant compared to that required for stabilising runny emulsions

A

The excess surfactants form structures in the bulk phase producing complex semi-solid multiphase systems

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16
Q

Creams structure (example) - 4 types

A
  1. Dispersed oil phase
  2. Bulk water phase
  3. Crystalline gel phase containing interlamellar fixed water
  4. Phase composed of crystalline hydrates of cetostearyl alcohol
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17
Q

What are creams prepared by?

A

in an o/w cream prepared by cetostearyl alcohol

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18
Q

Explain the cream structure;
21 slide

A
  • Surface of oil droplet (surrounded by surfactants and co-surfactants) > water > bilayer > preservative

IN REALITY there is a micelle between the surface of oil and the bilayer ( in the water) - similar to a micelles but an oval shape

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19
Q

Which one is the oiliest [b]+ watery [b]?
Ointment vs cream vs lotion

A

a) Ointment
b) Lotion

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20
Q

Why is ointment is able to trap ointment into the skin easier than lotion?

A

It traps more moisture in the skin
however greasy emollients are often less acceptable or tolarated

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21
Q

Breakdown on Creams, lotions and ointments

A

Creams are less greasy but generally more acceptable than ointments

Lotions are good for very mild dry skin and for the face. They can also be used in hairy places where the application of ointments or thicker creams can be quite messy!

Ointments should not be used where an infection is present (unless it is an antibiotic ointment)

Over-use of greasy ointments can lead to folliculitis (blockage and inflammation of hair follicles)

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22
Q

Dye solubility test

A

Mix emulsion with a water-soluble dye (amaranth) and observed under the microscope.

Continuous phase appears red > o/w type
Scattered globules appear red > w/o type

23
Q

Conductivity of emulsions (Emulsion – o/w or w/o)

A

Based on the electrical conductivity of aqueous solutions, the electric current is supplied through electrodes placed in the emulsion

If the current is passed > o/w type
Not passed > w/o type

24
Q

Fluorescence (Emulsion – o/w or w/o)

A

Based on the fluorescence of oils under ultraviolet light, examined under the light in the microscope

Whole fluid is fluorescent > w/o type
Spotty fluorescence > o/w type

25
Q

Hydrophile-lipophile balance (HBS system)

A

An empirical approach to aid the choice of surfactant(s) for a particular purpose, devised by Griffin in 1949

26
Q

Matching stragedy:

A

For emulsification, the strategy is to match the HLB of the surfactants to the HLB of the oil phase being emulsified

27
Q

Many surfaces may possess the same HLB value therefore>

A

Experiments are performed to find the best emulsifying system

28
Q

The HLB of a surfactant is expressed using an arbitrary scale

A

For non-ionic surfactants HLB ranges from 0 to 20
HLB = 7 + Σ(hydrophilic group no) – Σ(hydrophobic group no)

29
Q

Higher HLB (> 10)

A

Hydrophilic surfactants
Act as solubilising agents, detergents and o/w emulsifiers

30
Q

Low HLB (1 – 10)

A

Lipophilic surfactants
Act as w/o emulsifiers

31
Q

Mixtures of surfactants with a high and low HLB usually provide _____stability

A

more

32
Q

1) Calculations:

A

What is the HLB of the mixture of 40% Span 60 (HLB = 4.7) and 60% Tween 80 (HLB = 14.9)

HLB = 0.4 x 4.7 + 0.6 x 14.9 = 10.82

33
Q

2) Calculate the HLB of the oil phase in the o/w emulsion: liquid paraffin 5 g (HLB 12), white wax 1 g (HLB 12), lanolin 10 g (HLB 10), glycerin 5 g and water to 100 g

A

HLB [12], [12], [10]
Fraction [5/16], [1/16], [10/16]
Fractional HLB [3.75], [0.75], [6.25]

Glycerin is a co-solvent (doesn’t have a HLB - not a part of the oil phase)

TOTAL HLB = 10.75

34
Q

3) In what proportions should SDS (HLB = 40) be mixed with Span 80 (HLB = 4.3) to obtain an HLB of 11.5?

A

HLB = 40(X) + 4.3(1 – X) = 11.5
X = 0.2

SDS = 0.2 or 20% of the mixture, therefore
Span 80 = 1 – 0.2 = 0.8 or 80% of the mixture

If need 10 g of surfactant, then a mixture of 2.0 g of SDS + 8.0 g of Span 80 would produce a HLB of 11.5

35
Q

4) From the formula below, what % of span 20 and potassium oleate should be used in the overall emulsion to match the HLB of the oily phase?

A

a) Beeswax (HLB 9) - 6%
Wool fat (HLB 10) - 9%
Liquid paraffin (HLB 12) - 15%
= Oil phase 30%

Emulsifying agents (containing span 20, HLB 8.6) Potassium oleate (HLB 20) - 5%

Water - to 100%

b) You need to calculate the HLB

Beeswax 6/30 (%) x 9 = 1.8
Wool fat 9/30 x 10 = 3
Liquid paraffin 15/30 x 12 = 6
TOTAL = 10.8

c) Then need to match the HLB of the surfactants to the HLB of the oil

HLB(span20)(X) + HLB(potassium oleate)(1–X)
= 10.8
8.6(X) + 20(1–X) = 10.8
8.6X + 20 – 20X = 10.8
11.4X = 9.2
X = 0.8

This is the fraction of span 20 in the span 20:potassium oleate mixture
In other words we need 80% span 20 and 20% potassium oleate
In the 5% emulsifying agent, that means 4% span 20 and 1% potassium oleate

d) From the formula below, what % of span 20 and potassium oleate should be use

Beeswax (HLB9) 6%
Wool fat (HLB10) 9%
Liquid paraffin (HLB12) 15%
Emulsifying agents (Containing Spam 20 (HLB8.6) + potassium oleate (HLB20)

In the 5% emulsifying agents = 4% span + 1% potassium oleate

Water

36
Q

Suspensions
R - Vs / Vt = h[infinity] / ho

A

Ratio R compares sedimentation layer volume (Vs) to total suspension volume (Vt)

Usually determined by measuring height of sedimented layer (h∞) against height of suspension (h0)

37
Q

deflocculated; which part of graph? slide 15 (suspension - dosage forms)

A

Vmax
when particles are not associated

38
Q

During flocculation;

A

particles come together attracted by weak forces to form flocs

39
Q

Pressure on the individual particles leads to ______ _______ of the particles at the bottom, irreversibility bound together to from a cake

A

close packing

40
Q

Flocculating agents

A

Caking of the suspension is usually prevented by including a flocculating agent in the formulation

41
Q

Electrolytes

A

Reduce electrical forces of repulsion

42
Q

Surfactants

A

Ionic and/or non-ionic
Hydrated layers around particles and formation of liquid bridges

43
Q

Polymers

A

Lyophilic polymers
Structured vehicles and interparticulate interactions

44
Q

Electrostatic effects

A

Electrical double layer of ions
Stern layer
Diffuse layer
Zeta potential = magnitude and type (+ or –) of the electrical potential at the slipping plane
Low zeta potential (0 to 5 mV) are prone to aggregate
Zeta potential > 30 mV tend to remain dispersed

45
Q

Electrostatic effects example

A

Controlled flocculation of a bismuth subnitrate suspension using dibasic potassium phosphate (KH2PO4) as a flocculating agent

46
Q

Entropic (steric)

A
  • when two particles come into close contact, polymer chains overlap
  • leads to loss in freedom of motion of the polymer chains (LOSS OF ENTROPY)

-situation is thermodynamically unfavourable and forces the droplets apart again

47
Q

Osmotic (salvation) forces

A
  • When two particles come into close contact the polymer chains start to overlap = concentrated
  • This induces an osmotic gradient in the solution: a concentrated polymer solution in the overlap region and a dilute solution in the bulk solution
    Water enters the concentrated region in an attempt to dilute it and in doing so forces the polymer chains (and droplets) apart
48
Q

Flocculated v Deflocculated systems

A

Flocculated systems:
Particles are aggregated
Fast sedimentation
“Fluffy” sediment
Large sedimentation volume

Deflocculated systems:
Particles remain as discrete units
Slower sedimentation
Compact sediment
Small sedimentation volume

49
Q

Entropic (steric) effects example

A

An attractive bridging force (a) is replaced with a repulsive steric force (b) in adsorbing polymer solutions when the concentration increases

50
Q

Repulsive forces (VR)

A

Suspended particles will come into contact during sedimentation
If the repulsive forces (VR) are large enough the particles slip past one another

51
Q

Attractive forces (VA) > (VR) (small)

A

Weakly attracted clusters form
Flocculation = ‘form into an aggregated lumpy or fluffy mass’
Re-disperse upon shaking

52
Q

Attractive forces (VA) > (VR) (large)

A
  • Close packed arrangement at the bottom of the container

Particles in the lowest layers are ‘pressed’ together by the weight of the particles above > Produces a course compact mass

The repulsive barrier can be overcome and ‘caking’ can ensue

A ‘caked’ suspension cannot be re-dispersed

53
Q

Caking definition:

A

when you cannot flocculate further (mix)

54
Q

Controlled flocculation

A

How to achieve controlled flocculation:
Particle size
Use of electrolytes to control the electrostatic repulsion
Addition of flocculating agents (and their concentrations)
Surfactants
Ionic – Zeta potential
Non-ionic bridging
Polymers
Bridging
Also increase viscosity

PMP-102 (49 decks)

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