PHARMACEUTICAL SUSPENSIONS AND EMULSIONS

PHARMACEUTICAL SUSPENSIONS AND EMULSIONS

• Emulsion: Liquid drug in liquid vehicle:

• Suspension: Solid drug in liquid vehicle

Coarse Dispersions

Oil-in-water emulsions (o/w) Water-in-oil (w/o)

(Lyophobic colloids)

Reasons for UseReasons for Use

Drug is insolubleDrug is more stable in

suspension or emulsionThere is a need to control the

rate of release of the drugDrug has bad taste (oral)

Routes of AdministrationRoutes of Administration

OralOcularOticRectalParenteralTopical

I. Formulation of SuspensionsI. Formulation of Suspensions

Wetting

Wetting agent

Well Formulated Suspension

Resuspend easily upon shaking Settle rapidly after shaking Homogeneous mix of drug Physically and chemically stable

during its shelf life Sterile (parenteral, ocular) Gets into syringe (parenteral, ocular)

“External” Forces Acting on Particles

V(-o)g

2-5 m

Gravity Brownian Movement

Sedimentation equilibrium: Gravity is neutralized by Brownian movement

Settling and Aggregation

The suspension shall form loose networks of flocks that settle rapidly, do not form cakes and are easy to resuspend.

Settling and aggregation may result in formation of cakes (suspension) that is difficult to resuspend or phase separation (emulsion)

flock

cake

Sediment Volume

F=0.5 F=1.0 F=1.5

F={volume of sediment Vu}/{original volume Vo}

•Vo

•Vu

•Vo

•Vu

DLVO: Optimal Distance

Distance

Energy

Attraction

RepulsionAttraction

No flocks can form

Controlled Flocculation

Zeta-potential

F=Vu/Vo

Caking CakingNon-caking

Flocculating Agent

+

+-

Flocculating agent changes zeta-potential of the particles (it can be electrolyte, charged surfactant or charged polymer adsorbing on a surface).

If the absolute value of the zeta-potential is too high the system deflocculates because of increased repulsion and the dispersion cakes.

II. Formulation of EmulsionsII. Formulation of Emulsions

Emulsification

Emulsifier

HLB and Use of SurfactantsHLB and Use of Surfactants

HLB ca. 1 to 3.5: AntifoamsHLB ca. 3.5 to 8: Water-in-Oil EmulsifiersHLB ca. 7 to 9: Wetting and spreading agentsHLB ca. 8 to 16: Oil-in-Water EmulsifiersHLB ca. 13 to 16: DetergentsHLB ca. 15 to 40: Solubilizers

Amphiphilic surfactants are characterized by the hydrophilic-lipophilic balance (HLB): a relative ratio of polar and non-polar groups in the surfactant

Required HLBRequired HLB

Calculate the required HLB for the oil phase of the following o/w emulsion: cetyl alcohol 15 g., white wax 1g. Lanolin 2 g, emulsifier (q.s.), glycerin 5 g. water 100 g.

Required HLB Fraction

(from reference)Cetyl alcohol 15 x 15/18 12.5White wax 12 x 1/18 0.7Lanolin 10 x 2/18 1.1Total required HLB 14.3

HLB needed for emulsification of the oil phase. If there are several oil ingredients the required HLB is calculated as a sum of their respective required HLB multiplied by the fraction of each.

HLB of Surfactant BlendHLB of Surfactant Blend

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

HLB of mixture:4.7 x 0.4 + 14.9 x 0.6 = 10.8

In what proportion should Span 80 (HLB = 4.3) and Tween 80 (HLB = 15.0) be mixed to obtain “required” HLB of 12.0?

4.3.(1-x) + 15.x = 12 x = 0.72 72 % Tween 80 and 28 % Span 80

Surfactant blends are commonly used to obtain desired emulsifying properties.