Disperse System Definition Dispersing phase Interface Dispersed phase Disperse Systems Pharmaceutical Unit size property agent Properties Surfactant Stability potential -amphiphakc rheology HLB value Xiaohui Wei Mochanism: Solubilization System micelle:CMC xhwei@sjtu.edu.cn Safety Three pharmaceutical suspension drug delivery systems emulsion 2 Formulation Study: liposome 4. Evaluation Mothod: 1.Introduction 2.Fundamental properties: 2.1.Classification Definition: 1.The Types of the dispersed phase /the dispersing Dispersed phase and Dispersing phase phase. The significance: 2. Molecular/Micellar dispersions be widely used in oral,tropical,parenteral drug delivery. 3 Spherical/Linear target delivery 1
1 Disperse Systems Xiaohui Wei xhwei@sjtu.edu.cn Disperse System Definition Dispersing phase Dispersed phase Interface Pharmaceutical Properties Unit size Stability rheology Zeta Safety, potential Effectiveness, Reliability; Given route Surfactant Electric property Stabilizing agent Three pharmaceutical systems suspension emulsion liposome amphiphilic HLB value Mechanism: micelle;CMC Safety 1. Vehicle properties for drug delivery 2. Formulation Study; 3. Preparation Method; 4. Evaluation Method; Solubilization System 1. Introduction Definition: Dispersed phase and Dispersing phase The significance: be widely used in oral, tropical, parenteral drug delivery. target delivery 2.Fundamental properties: 2.1.Classification 1. The Types of the dispersed phase / the dispersing phase. 2. Molecular / Micellar dispersions 3 Spherical/ Linear
Classification based on the types of the dispersed phase Classification of Dispersed systems based on Particle Size the dispersing phase. Class Particle Size Examples S-L L-L G-L Molecular <1 nm(mu) oxygen molecules, Dispersion ions,glucose S-S L-S G-S S-GL-GG-G Colloidal 0.5m- colloidal Ag sols,natural Suspensions:S-S,L-S(OR S-L),G-S Dispersion 1.0mv synthetic polymer,milk Emulsion: LL Coarse >0.5μm R.B.C.,Pharmaceutical Dispersion emulsions,suspensions Questions 2.2 Fundamental Properties: Particle Size Distribution The size of the dispersion unit? Expression: Eguivalent Spherical Diameter 。The stable period? Determination Method: QELS(PCS)Method Coulter Counter Method For the liquid dispersion system,what kind of rheological properties it has Data Presentation: by volume/number/intensity polydispersion index 2
2 Classification based on the types of the dispersed phase / the dispersing phase. S-L L-L G-L S-S L-S G-S S-G L-G G-G Suspensions: S-S, L-S (OR S-L), G-S Emulsion: L-L Class Particle Size Examples Molecular <1 nm(mµ) oxygen molecules, Dispersion ions, glucose Colloidal 0.5 µm - colloidal Ag sols, natural & Dispersion 1.0 mµ synthetic polymer, milk Coarse >0.5 µm(µ) R.B.C., Pharmaceutical Dispersion emulsions, suspensions Classification of Dispersed systems based on Particle Size Questions z The size of the dispersion unit? z The stable period? z For the liquid dispersion system, what kind of rheological properties it has ? 2.2 Fundamental Properties: Particle Size & Distribution Expression: Equivalent Spherical Diameter Determination Method: QELS(PCS) Method Coulter Counter Method Data Presentation: by volume/number/intensity polydispersion index
2.3.Fundamental Properties: The Surface Properties Crystal Growth Significance: Nal AgNO3 physical stability excess →Agll+Nat+NO Zeta potential: definition:unit charge from infinity to the fixed layer; negatively charged charge:adsorption or ionization:crystal lattice extension ⊙g个g colloidal particle diffuse double layer:fixed layer and mobile diffuse layer Determination:electrophoresis method From "CoMloidal Systems"by R Gary Hollenbeck,Ph.D. Particle Surface Stern Layer(fixed layer) Shear plane Gouy-Chapman Layer Particle Surface ⊙ 1 ⊙ Bulk Solution ⊙ @ ⊙ Equal concentration ⊙ of similions and counterions o NO NO Di折se Double Layer From "Colloidal Systems"by R.Gary Hollenbeck,Ph.D. Diffuse Double Layer FromColloidal Systems"by R Gary Hollenbeck,Ph.D. 卡 Distance from particle surface Distance from particle surface 3
3 2.3. Fundamental Properties: The Surface Properties Significance: physical stability Zeta potential: definition: unit charge from infinity to the fixed layer; charge: adsorption or ionization; crystal lattice extension diffuse double layer: fixed layer and mobile diffuse layer Determination: electrophoresis method Crystal Growth NaI + AgNO AgI + Na + NO excess 3 + 3 - NO3 - NO3 - NO3 - Na+ Na+ Na+ Na+ Na+ Na+ Na+ NO3 - NO3 - Na+ NO3 - NO3 - NO3 - Na+ Na+ Na+ Na+ I - I - I - I - Ag Ag + + Ag+ I - I - Ag+ I - I - I - I - Ag Ag + + Ag+ I - I - Ag+ I - I - I - I - I - I - I - negatively charged colloidal particle From “Colloidal Systems” by R. Gary Hollenbeck, Ph.D. I - I - I - I - I - I - I - Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na Na+ + NO - 3 NO - 3 NO - 3 NO - 3 NO - 3 Na+ Particle Surface Stern Layer (fixed layer) Gouy-Chapman Layer Distance from particle surface Bulk Solution Equal concentration of similions and counterions Diffuse Double Layer Na+ Na+ I - I - From “Colloidal Systems” by R. Gary Hollenbeck, Ph.D. I - I - I - I - I - I - I - Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na Na+ + NO - 3 NO - 3 NO - 3 NO - 3 NO - 3 Na+ Particle Surface Distance from particle surface Diffuse Double Layer Na+ Na+ I - I - NO - 3 From “Colloidal Systems” by R. Gary Hollenbeck, Ph.D. Shear plane
From Colloidal Systems"by Shear plane R Gary Hollenbeck,Ph_D. 2.4.Rheological Properties Particle Surface 平o RHEOLOGY Zota Potentlal Surface Potontial rheo-to flow Dynamic potential Ther logos-science To the shear plane To the particle Influenced by the Rheology describes the flow of liquids and the deformation of solids. Ψz=Zeta potential :Ψ=0 Distance from particle surface 2.4.Rheological Properties Five main types: Significance: related to tropical use and stability Rheological type Example Mixding .Flow of materials -Packaging into containers Simple Newtonian Fluid solution -romoval prior to use Plastic Fluid flocculated Suspension. Classification:the Newton Equiv. Yield Value shear rate(velocity gradient) Simple Pseudoplastic Fluid polymer solution shear stress viscosity coefficient (Shear-thinning systems) Dilatant Fluid Suspensions containing a high Measurement:viscometer and empirical data concentration (50%or greater)of (Shear-thickening systems) small,deflocculated particles. thixotropy 4
4 I - I - I - I - I - I - I - Particle Surface Distance from particle surface Shear plane Ψo Ψ=0 Ψz = Zeta potential From “Colloidal Systems” by R. Gary Hollenbeck, Ph.D. To the particle surface To the shear plane Influenced by the iron on the particle surface Influenced by other irons Thermodynamic potential Dynamic potential Zeta Potential Surface Potential 2.4.Rheological Properties RHEOLOGY rheo - to flow logos – science Rheology describes the flow of liquids and the deformation of solids. 2.4.Rheological Properties Significance: related to tropical use and stability - Mixing - Flow of materials - Packaging into containers - removal prior to use Classification: the Newton Equiv. shear rate( velocity gradient) shear stress viscosity coefficient Measurement: viscometer and empirical data Five main types: thixotropy Suspensions containing a high concentration (50% or greater) of small, deflocculated particles. Dilatant Fluid (Shear-thickening systems) Simple Pseudoplastic Fluid polymer solution (Shear-thinning systems) flocculated Suspension, Yield Value Plastic Fluid Simple Newtonian Fluid solution Rheological type Example
3.Solubilized Systems 3.1 Surfactant Solubilization:the process to increase the apparent solubility There are molecules or ions that have both lipophilic and lipophoblc (or hydrophilic)groups in the same molecule. The related manipulations: These substances are caled amphiphiles and atso surface 1.Surfactant micelles (micellar solubilization) active agents due to their ability to lower the surface or intertacial tension of the meaum in which they are dissolved. 2.Cosolvents 3.complexation M● 4.Solid-state changes Nonpolar or lipophilic group: Le.hydrocarbon chain Polar or hydrophilic group 5.Hydrotropic agents 6.Prodrug formation Depending on the nature of the polar groups.amphiphiles can be anionic.cationic.nonionic.or ampholytic. 3.1.1Chemical classification 3.1.2 Physical Classification Type Examples Solubizers Anionic Sodium Laureate (SDS) ge CHa(CH2)++OSO:Na' 09 Cationic CTAB.with antimicrobial activity CHa(CH2)asN"(CHa)3 Br lipophilic hydrophilic Nonionic Polymeric surfactants such as Tween /Span,Pluronic The hydrophilic-lipophilic balance (HLB)is a measure (in an arbitrary scale)of the ratio Leeehin between the polar and non-polar groups (or Amphoteric zones)in the surfactant molety.The higher the HLB the more polar the surfactant. 5
5 3.Solubilized Systems Solubilization: the process to increase the apparent solubility The related manipulations: 1. Surfactant micelles (micellar solubilization) 2. Cosolvents 3. complexation 4. Solid-state changes 5. Hydrotropic agents 6. Prodrug formation 3.1 Surfactant 3.1.1Chemical classification Amphoteric Polymeric surfactants such as Tween /Span, Pluronic Nonionic CTAB, with antimicrobial activity CH3(CH2)15N+(CH3)3 BrCationic Sodium Laureate (SDS) CH3(CH2)11OSO3-Na+ Anionic Type Examples 3.1.2 Physical Classification