PHARMACEUTICAL SUSPENSIONS AND EMULSIONSPHARMACEUTICAL SUSPENSIONS AND EMULSIONS EmuIsion: Liquid drug in liquid vehicle: Suspension: Solid drug in liquid vehicleCoarse Dispersions Oil-in-water emulsions (o/w)Water-in-oil (w/o)(Lyophobic colloids)Reasons for Use Reasons for Use Drug is insoluble Drug is more stable in suspension or emulsion There is a need to control the rate of release of the drug Drug has bad taste (oral)Routes of Administration Routes of Administration Oral Ocular Otic Rectal Parenteral TopicalI. FormuIation of SuspensionsI. FormuIation of SuspensionsettingWetting agenteII FormuIated SuspensionResuspend easily upon shakingSettle rapidly after shakingHomogeneous mix of drugPhysically and chemically stableduring its shelf lifeSterile (parenteral, ocular)Gets into syringe (parenteral, ocular)ExternaI" Forces Acting on ParticIesV(8-8o)g2-5 3mGravityBrownian MovementSedimentation equilibrium: Gravity is neutralized by Brownian movementSettIing 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 ofcakes (suspension) that is difficult to resuspend orphase separation(emulsion)flockcakeSediment VoIumeF=0.5 F=1.0 F=1.5F={volume of sediment Vu}/{original volume Vo}VoVuVoVuDLVO: OptimaI DistanceDistanceEnergyAttractionRepulsionAttractionNo flocks can formControIIed FIoccuIationeta-potentialF=Vu/VoCaking CakingNon-cakingFlocculating Agent++- Flocculating agent changes zeta-potential of the particles (it can be electrolyte, charged surfactant or charged polymer adsorbing on a surface). f the absolutevalue of the zeta-potential is too high the system deflocculates because of increased repulsionandthe dispersion cakes.II. FormuIation of EmuIsionsII. FormuIation of EmuIsionsEmuIsificationEmulsifierHLB and Use of Surfactants HLB and Use of SurfactantsHLB 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: SolubilizersAmphiphilic surfactants are characterized by the hydrophilic-lipophilic balance (HLB): a relative ratio of polar and non-polar groups in the surfactantRequired HLB Required HLBCalculate 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 HLBFraction(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 14.3HLB needed for emulsification of the oil phase. f 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 Blend HLB of Surfactant Blendhat 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 = 10.8In 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 80Surfactant blends are commonly used to obtain desired emulsifying properties.