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Coarse Dispersion, Emulsions

Coarse Dispersion, Emulsions

University of Sulaimani School of Pharmacy Dept. of Pharmaceutics Third level - Second semester

Coarse dispersion,

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 1 Outlines

• Introduction • Theories and mechanisms • Emulsifying agents • HLB system • Methods of preparation • Microemulsion • Stability of emulsions • Common features and differences

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 2 Introduction • An emulsion is a dispersion in which the dispersed is composed of small globules of a distributed throughout a vehicle in which it is immiscible. • Depending on external and internal phase, emulsions are either in oil (w/o) or oil in water (o/w) type. • The third phase of an emulsion is the emulsifying agent • Can we dilute emulsion? water Emulsifier W/O O/W Oil

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 3 Introduction cont.

• Based on the constituents and the intended application, liquid emulsions may be employed orally, topically (sometime semisolid), or parenterally.

• Advantages of emulsion • Preparation of relatively stable and homogeneous mixtures of two immiscible • The o/w type permits palatable administration of distasteful oil. • The reduced particle size of the oil globules may render the oil more digestible and more readily absorbed

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 4 Outlines

• Introduction • Theories and mechanisms • Emulsifying agents • HLB system • Methods of emulsion preparation • Microemulsion • Stability of emulsions • Common features and differences

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 5 Theories and mechanisms

1. Surface tension theory • All liquids have a tendency to assume a shape having the minimal surface area exposed i.e. sphere. • If two or more drops of the same liquid come into contact with one another, making one larger drop having a smaller surface area i.e. coalescence . • ΔG = γ * ΔΑ • The force causing each liquid to resist breaking up into smaller particles is called interfacial tension.

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 6 Theories and mechanisms cont.

• Substances that reduce this resistance (encourage a liquid to break up into smaller drops or particles) is called surface-active (surfactant) or wetting agents.

2. The oriented-wedge theory • It assumes monomolecular layers of emulsifying agent curved around a droplet of the internal phase of the emulsion. • The phase in which the emulsifying agent is more soluble will become the continuous or external phase • An emulsifying agent having a greater hydrophilic than hydrophobic character will promote an o/w emulsion.

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 7 Theories and mechanisms cont. Film type Example Mechanism A. Monomolecular Synthetic like, • The film is flexible. Potassium laurate • They lower the interfacial tension, and thus Tween contributes to stability of emulsion.

B. Multimolecular Natural like • The film is strong and rigid film formed Acacia, Gelatine • The Interfacial tension is not reduced.

C. particles Bentonite • Film formed by solid particles that are small in size Magnesium hydroxide compared to the dispersed droplet. • Particles must be wetted by both phases to some extent.

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 8 Outlines

• Introduction • Theories and mechanisms • Emulsifying agents • HLB system • Methods of emulsion preparation • Microemulsion • Stability of emulsions • Common features and differences

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 9 Emulsifying agents

• Features of emulsifying agents • The emulsifying agent must be compatible with the other ingredients • It should be stable • It should be non toxic and possess a little color, odor, and taste. • It should be surface active and decrease interfacial tension • It should be effective in a fairly low concentration

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 10 Emulsifying agents

1. Carbohydrate materials like acacia, tragacanth, agar, and pectin generally produce o/w emulsions. • Tragacanth and agar are commonly employed as thickening agents in acacia- emulsified products • Needs addition of 0.2% of benzoic acid.

2. High molecular weight alcohols, such as stearyl alcohol, cetyl alcohol, and glyceryl monostearate. • Usually they are used externally • Cholesterol is used to promote w/o emulsions.

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 11 Emulsifying agents cont.

3. Wetting agents, which may be anionic, cationic, or nonionic • These agents contain both hydrophilic and lipophilic groups • Anionic emulsifiers include various monovalent, polyvalent, like sodium lauryl sulfate • Benzalkonium chloride is an example for cationic emulsifier • Agents of the nonionic type include the sorbitan esters and the polyoxyethylene derivatives, • Cationic surfactants are effective over pH range of 3 to 7, and anionic surfactants require a pH greater than 8.

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 12 Emulsifying agents cont.

4. Finely divided such as colloidal clays, including bentonite, magnesium hydroxide, and aluminum hydroxide

• Inversion • Is changing of emulsion from o/w to w/o as a result of increased internal phase. • Maximum limit of the internal phase is 75%.

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 13 Outlines

• Introduction • Theories and mechanisms • Emulsifying agents • HLB system • Methods of emulsion preparation • Microemulsion • Stability of emulsions • Common features and differences

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 14 HLB system

• Emulsifying agent has a hydrophilic portion and a lipophilic portion, predominance of each portion is influence the type of emulsion. • Emulsifying agent could be categorized on the base of their hydrophilic-liphophilic balance HLB system. • The usual range is between 1 and 20. • Higher polarity → higher the value • Agents with HLB value of 3 to 6 are greatly lipophilic and produce w/o emulsions • Agents with HLB values of about 8 to 18 produce o/w emulsions.

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 15 HLB system cont.

Emulsifier HLB value

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 16 Outlines

• Introduction • Theories and mechanisms • Emulsifying agents • HLB system • Methods of emulsion preparation • Microemulsion • Stability of emulsions • Common features and differences

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 17 Methods of emulsion preparation • On a small scale, emulsions may be prepared using porcelain mortar and pestle. • The product may be rendered finer by passage through a mill. 1. Continental or dry gum method Ratios of Oil: Water: Emulsifier Fixed oils except liquid Linseed oil, liquid Emulsifying agent petrolatum and linseed oil petrolatum and volatile oils Acacia 4:2:1 3:2:1 or 2:2:1 Tragacanth 40:20:1 30:20:1 or 20:20:1 • The acacia or other o/w emulsifier is triturated with the oil in a dry porcelain (better than glass) mortar until thoroughly mixed. • After oil-gum mixing, the two parts of water are added all at once, and the mixture is triturated immediately → primary emulsion produces a crackling sound (3 min). • of other ingredients is added into the primary emulsion.

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 18 Methods of emulsion preparation cont.

2. English or wet gum method • Same proportions of oil, water, and gum are used as in dry gum method. • The order of mixing is different. • water+acacia trituration → add oil slowly.

3. Bottle method • It is used for volatile oils or less viscous oils. • (1 acacia+ 2 oil)→ shaking in a capped bottle. Then adding water equal to the oil. Auxiliary • Homogenizer → 5 μm

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 19 Methods of emulsion preparation cont.

4. In situ method • This method includes calcium and soft soaps. • Calcium soaps are w/o emulsions that contain certain vegetable oils, such as oleic acid, in combination with limewater (Calcium Hydroxide Solution, USP). • They are prepared by mixing equal volumes of the oil and limewater.

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 20 Outlines

• Introduction • Theories and mechanisms • Emulsifying agents • HLB system • Methods of emulsion preparation • Microemulsion • Stability of emulsions • Common features and differences

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 21 Microemulsion

• They are thermodynamically stable, optically transparent mixtures of a biphasic o/w system stabilized with surfactants. • Droplet size 10-100 nm. • The surfactant is commonly called solubilizing agent. • Advantages • More rapid and efficient oral absorption of drugs • Enhanced transdermal drug delivery through increased into the skin. • Development of artificial red cells and targeting of cytotoxic drugs to cancer cells

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 22 Outlines

• Introduction • Theories and mechanisms • Emulsifying agents • HLB system • Methods of emulsion preparation • Microemulsion • Stability of emulsions • Common features and differences

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 23 Stability of emulsions

• Freezing and excessive heat coarsen an emulsion and sometimes break it. • Fungistatic preservatives, commonly combinations of methylparaben and propylparaben, are generally included in the aqueous phase of an o/w emulsion.

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 24 Stability of emulsions cont.

• An emulsion is considered to be physically unstable if: a. The internal phase upon standing tends to form aggregates of globules b. Large globules or aggregates of globules rise to the top or fall to the bottom of the emulsion c. If the internal phase separates and forms a distinct layer on the top or bottom of the emulsion.

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 25 Creaming

• Creaming is aggregates of globules of the internal phase that rise to the top of the emulsion or fall to the bottom. • It is a reversible process • A creamed emulsion is not esthetically acceptable

• Thickeners such as tragacanth and MCC are frequently added to emulsions to increase the viscosity of the external phase.

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 26 Coalescence

• More destructive to an emulsion is coalescence of the globules of the internal phase and separation of that phase into a layer. • Separation of the internal phase from the emulsion is called breaking, and the emulsion is described as being cracked or broken.

• Coalescence and breaking are irreversible.

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 27 Outlines

• Introduction • Theories and mechanisms • Emulsifying agents • HLB system • Methods of emulsion preparation • Microemulsion • Stability of emulsions • Common features and differences

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 28 Common features and differences between suspensions and emulsions

• Common features • Suspensions and emulsions contain particles, solid and liquid respectively, dispersed in a continuous phase. • They are both subject to processes • The factors that influence the sedimentation rate, operate to the same extent in both. • Both systems require some input of energy to disperse the particles

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 29 Common features and differences

• Common differences • The major difference is that the particles of the emulsion are liquid droplets, whereas those of the are solid. • In emulsion, droplet aggregation caused coalescence, in suspension caused . • Dissolved drug in oil phase of emulsion is ready for absorption, drug solid particles need dissolution.

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 30 Thank you

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 31

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