Methods of Preparation 1.

Continental or Dry gum method The method is also referred to as the 4:2:1 method because for every 4 parts (volumes) of oil, 2 parts of water and 1 part of gum are added in preparing the initial or primary emulsion. For instance, if 40 mL of oil are to be emulsified, 20 mL of water and 10 g of gum would be employed, with additional water or other formulation ingredients being added afterward to the primary emulsion Preparation of Continental or Dry Gum Method 1. The acacia or other O/W emulsifier is triturated with the oil in a perfectly dry Wedgewood or porcelain mortar until thoroughly mixed. 2. After the oil and gum have been mixed, the two parts of water are then added all at once, and the mixture is triturated immediately, rapidly, and continuously until the primary emulsion that forms is creamy white and produces a crackling sound to the movement of the pestle 3. Generally, about 3 minutes of mixing are required to produce such a primary emulsion. 4. Other liquid formulative ingredients that are soluble in or miscible with the external phase may then be added to the primary emulsion with mixing. 5. Solid substances such as preservatives, stabilizers, colorants, and any flavoring material are usually dissolved in a suitable volume of water and added as a solution to the primary emulsion NOTE: A mortar with a rough rather than smooth inner surface must be used to ensure proper grinding action and the reduction of the globule size during the preparation of the emulsion. A glass mortar has too smooth a surface to produce the proper size reduction of the internal phase.

2. English or wet gum method -The same proportions of oil, water, and gum are used as in the dry method, but the order of mixing is different, and the proportion of ingredients may be varied during the preparation of the primary emulsion as is deemed necessary by the operator. 3. Bottle or Forbes bottle method -For the extemporaneous preparation of emulsions from volatile oils or oleaginous substances of low viscosities, the bottle method is used. (2:2:1) Preparation: 1. The powdered acacia is placed in a dry bottle

2.

Two parts of oil is then added, and the mixture is thoroughly shaken in the capped container.

3. A volume of water approximately equal to the oil is then added in portions 4. The mixture being thoroughly shaken after each addition 5. When all of the water has been added, the primary emulsion thus formed may be diluted to the proper volume with water or other an aqueous solution of other formulative agents NOTE: This method is not suited for viscous oils, because they cannot thoroughly agitated in the bottle. 4. Auxiliary method -An emulsion by either the wet gum or dry gum methods can generally be increased in quality by passing it through a hand homogenizer. -In this apparatus, the pumping action of the handle forces the emulsion through a very small orifices which reduces the globules of the internal phase to about 5 um and sometime less

5. In SITU soap method Two types of soap developed by this method are Calcium soaps and Soft soaps. Calcium soaps - water - in - oil emulsions which contain certain vegetable oil (e.g. Oleic acid) in combination with lime water ( Syn: Calcium Hydroxide Solution USP) and prepared by mixing equal volumes of the oil and lime water Example: Calamine Liniment (itchy, dry skin, sunburn) Calamine Zinc Oxide . Olive oil Calcium Hydroxide Soln aa q.s ad 1000.0 mL 6. Microemulsions Thermodynamically stable, optically transparent, isotropic mixtures of a biphasic oilwater system stabilized with surfactants. The diameter of droplets in a microemulsion may be in the range of 100 A (10 microns) to 1000 A whereas in a microemulsion the droplets may be 5000 angstroms in diameter. 80.0 g

 Both O/W and W/O microemulsions may be formed spontaneously by agitating the oil and water phases with carefully selected surfactant. Advantages: More rapid and efficient oral absorption of drugs than through solid dosage forms Enhance transdermal drug delivery through increased drug diffusion into the skin The technique potential application of microemulsion in the development of artificial red blood cells and in the argeting of cytotoxic drugs to cancer cells

Stability of emulsions An emulsion is considered to be physically unstable if: -The internal or dispersed phase upon standing tends to form aggregates of globules. -Large globules or aggregates of globules rise to the top or fall to the bottom of the emulsion to form concentrated layer of the internal phase. -If all or part of the liquid of the internal phase becomes unemulsified and forms a distinct layer on the top or bottom of the emulsion as result of the coalescing of the globules of the internal phase Aggregation and Coalescence Creaming - is the rising (upward creaming) or settling (downward creaming) of globules or floccules to form a concentrated layer at the surface or to the bottom of the emulsion -The creamed portion of an emulsion may be redistributed rather homogeneously upon shaking -if the aggregates are difficult to disassemble or if insufficient shaking is employed before each dose, improper dosage of the internal phase substance may result -a creamed emulsion is not esthetically acceptable to the pharmacist o appealing to the customer According to strokes equation, the rate of separation of the dispersed phase of an emulsion may be related to such factors as the particle size of the dispersed phase, the difference in density between the phases, and the viscosity of the external phase -therefore, to increase the stability of an emulsion, the globule or particle size should be reduced as fine as is practically possible

(thickeners)Tragacanth and Microcrystalline cellulose- added to emulsion to increase the viscosity of the external phase

Affect the stability of emulsion -Presence of light, air and contaminating microorganism Examples of Oral emulsions Mineral Oil emulsion(liquid petrolatum emulsion)- is an oil in water emulsion prepared from mineral oil,acaia,syrup,vanillin,alcohol and purified water -it is prepared by the dry gum method (4:2:1) -the emulsion is employed as a lubricating cathartic with a usual dose of 30ml Castor Oil emulsion -used as laxative and in preparation of the colon for radiography and endoscopic examination -should not be used regularly or excessively (bec. it can lead to dependence for bowel movement) -overuse of castor oil may cause excessive loss of water and body electrolyte which can have debilitating effect -laxative should not be used when nausea, vomiting or abdominal pain is present( bec. this symtoms may indicate appendicitis, and could promote rupturing of the appendix) -it is best taken on an empty stomach, followed with one full glass of water Simethicone Emulsion -is a water-dispersible form of simethicone used as a defoaming agent for the relief of painful symptoms of excessive gas in the gastrointestinal tract. -simethicone is also present in a number of antacid formulations as a therapeutic adjunct to relieve the discomfort of gas Ex. Mylicon drops,astraZenica

Examples of topical emulsions

Estrasorb- use in the treatment of hot flashes and night sweats accompanying menopause

Corticosteroid-containing emulsion Lotriman AF Diprolene Gels and Magmas

Gels- Semisolid systems consisting of dispersions made up of either small inorganic particles or large organic molecules enclosing and interpenetrated by a liquid - Semirigid systems in which the movement of the dispersing medium is restricted by an interlacing three dimensional network of particles or solvated macromolecules of the dispersed phase *The increased viscosity caused by the interlacing and consequential internal friction is responsible for the semisolid state Single-phase gels- gels in which the macromolecules are distributed so that no apparent boundaries exist between them and the liquid Magma or a milk- When the gel mass consists of floccules of small distinct particles. Also classified as two phase system Colloidal dispersions Sol- general term to designate a dispersion of a solid substance in a liquid, solid, or gaseous medium Prefix employed to indicate the dispersion medium 1) Hydro (hydrosol)- for water 2) Alco (alcosol)- for alcohol Difference between colloidal dispersions and true solutions Particle size (colloidal-larger) Optical Properties (true-do not scatter light-clear, colloidal-scatter light-turbid)

Attraction between the phases of a colloidal dispersion

Lyophilic- Solvent loving (interacts w/ the dispersion medium, easier to prepare) Lyophobic- Solvent hating (if the degree attraction is small)

Hydrophilic- attraction of substance to water

Hydrophobic- lack of attraction of substance to water Association or amphiphilic colloid- formed by grouping or association of molecules that exhibit both lyophilic and lyophobic properties

Imbibition

is taking up of a certain amount of liquid without a measurable increase by a gel with an increase volume. is the taking up of a liquid by a gel with an increase in volume. Only those liquid that solvate a gel can cause swelling. The swelling of protein gels is influenced by pH and thepresence of electrolytes. is when the interaction between particles of the dispersed phase becomes so great than on standing, the dispersing medium is squeezed out in droplets and the gel shrinks. Syneresis is a form of instability in aqueous and nonaqueous gels

Swelling

Syneresis

Terminology related to Gels

Thixotrophy

is a reversible gel-sol formation with no change in volume or temperature-a type of non-Newtonian flow. is formed when the liquid is removed from a gel and only the framewok remains. Examples: gelatin sheet, tragacanth ribbons and acacia tears

Xerogel

Classification and types of gels First classification scheme: 1) Inorganic hydrogels- are usually two phase systems such as Aluminum Hydroxide Gel and Bentonite Magma 2) Organic gels- are usually single phase systems and may include such as gelling agents as Carbomer and Tragacanth and those that contain an organic liquid, such Plastibase. Second classification scheme 1) Hydrogels - include ingredients that are dispersible as colloidals or soluble in water and include organic hydrogels, natural and sythetic gums and inorganic hydrogels Examples: silica, bentonite, tragacanth, pectin, sodium alginate, methylcellulose, sodium carboxymethylcellulose and alumina 2) Organogels - include the hydrocarbons, animal and vegetable fats, soap base greases and the hydrophilic organogels. Examples: Hydrocarbon - Jelene, or Plastibase Jelies- class of gels in which structural coherent matrix contains high proportion of liquid usually water - subject to bacterial contamination and growth, so most are preserved with antimicrobials - should be stored with tight closure, because water may evaporate, drying out the product

Preparation of magmas and gels 1. By freshly precipitating the disperse phase 2. By direct hydration in water

Examples of gelling agents 1. Acacia 2. Bentonite 3. Carbocymethylcellulose sodium 4. Colloidal silicon dioxide 5. Gelatin 6. Hydroxyethylcellulose 7. Hydroxypropryl methylcellulose 8. Maltodextrin 9. Polyvinyl alcohol 10. Propylene carbonate 21. Sodium starch glycolate 23. Tragacanth 11. Alginic acid 12. Carbomer 13. Cetostearyl Alcohol 14. Ethylcellulose 15. Guar gum 16. Hydroxypropryl cellulose 17. Magnesium aluminum silicate 18. Methylcellulose 19. Povidone 20. Sodium alginate 22. Starch 24. Xanthan gum

1. Alginic acid- obtained from seaweed, prepared products is tasteless, odorless, yellowish-white colored fibrous powder -used as thickening agent in concentrations of 1 to 5% -swells in water to about 200 to 300 times its own weight without dissolving 2. Carbomer (Carbopol)- resins with high molecular weight allylpentaerythritol-crosslinked acrylic acid-based polymers modified with C10 to C30alkyl acrylates fluffy white powders with large bulk density (0.5 and 1% aqueous dispersion)

Example: Carbomers 910,934,934P,940 and 1342 3. Carboxymethylcellulose - concentrations of 4 to 6% of medium viscosity can be used to produce gel; glycerin may be added to prevent drying; incompatible with alcohol 4. CMC sodium- soluble in water at all temperature 5. Colloidal silicone dioxide- can be used with other ingredients of similar refractive index to prepare transparent gels 6. Gelatin- dispersed in hot water and cooled to form gels

7. Magnesium aluminum silicate (Veegum)- concentrations of about 105 forms a firm thixotropic gel material is inert and has few incompatibilities but is less used above pH 3.5

8. Methylcellulose- long-chain substituted cellulose that can be used to form gels in concentration up to 5% - dispersed with high shear in about 1/3 of water 9. Plastibase (Jelene)- mixture of 5% low molecular weight polyethylene and 95% mineral oil 10. Poloxamer (Pluronic)- concentrations ranging from 15 to 50% to form gel poloxamers 124 (L-44 grade), 188 (F-68 grade), 237 (F-87 grade), 338 (F-108 grade) and 407 (F-127 grade) types are freely soluble in water F = refers to flake form L = refers to liquid form 11. Polyvinyl alcohol (PVA)- used at concentrations of about 2.5% in the preparartion of various jellies that dry rapidly when applied to the skin - borax is a good agent that will gel PVA solutions - for best result, dispersed PVA in cold water, followed by hot water. It is less soluble in cold. 11. Povidone - about 10% in concentrations to prepare gels also increase solubility of poorly soluble drugs -

12. Sodium alginate- 10 % to produce gels aqueous preparations are most stable at pH 4 to 10; below pH 3, alginic acid is precipitated

13. Tragacanth gum-used to prepare gels that are most stable at pH 4 to 8 must be preserved with 0.1% benzoic acid or .17% methylparaben and 0.03% propyl paraben

Gel Formulation Considerations -polymer solutions tend to be cast as gels because the solute consists of long, flexible chain of molecules -Inorganic salts will compete with the water in a gel and cause gelatin at lower concentrations -Aqueous polymer solutions, especially of cellulose derivatives are stored for approximately 48hours after dissolution to promote full hydration and maximum viscosity and clarity.

Examples of magmas and gels

Bentonite Magma Sodium Fluoride and Phosphoric Acid Gel Fluocinonide Gel Tretinoin Gel Erythromycin and Benzoyl peroxide Gel

NF USP

suspending agent dental care prophylactic

USP USP

Anti-inflammatory corticosteroid treatment for acne

Clindamycin Topical Gel Hydroquinone Gel Salicylic acid Gel Desoximethasone Gel Aluminum Phosphate Gel (Amphogel) Aluminum hydroxide Gel Dihydroxyaluminum Aminoacetate Magma Milk of Magnesia (Magnesia Magma) USP Hyperpigmented skin keratolytic anti-inflammatory and antipruritic agent antacid

USP

antacid

USP

antacid

USP

Antacid; laxative