Pharmaceutical Technology II Emulsions PDF

Pharmaceutical Technology II Emulsions Chapter 14: Disperse Systems Water Oil Chapter 14| Disperse Systems : Emulsions Contents : Emulsion 5 Emulsion Types 8 Macroemulsions vs. Microemulsions 12 Determination tests of the emulsion type 16 Theories of Emulsification 31 Preparation of Emulsions 37 Cri...

Pharmaceutical Technology II Emulsions Chapter 14: Disperse Systems Water Oil Chapter 14| Disperse Systems : Emulsions Contents : Emulsion 5 Emulsion Types 8 Macroemulsions vs. Microemulsions 12 Determination tests of the emulsion type 16 Theories of Emulsification 31 Preparation of Emulsions 37 Criteria for Selecting Emulsifying Agents 38 Common Types of Emulsifying Agents 41 HLB System 51 Preparation Methods 67 Stability of Emulsions 87 Preservation of emulsion 100 Therapeutic examples 102 Chapter 14| Disperse Systems : Emulsions Objectives : After reading this topic, the student will be able to: Define the pharmaceutical emulsions Distinguish between the different types of pharmaceutical emulsions based on their physical state Differentiate between the different types of pharmaceutical emulsions based on their intended uses. Chapter 14| Disperse Systems : Emulsions Objectives : After reading this topic, the student will be able to: Compare and contrast emulsification theories: surface tension, oriented wedge, and Interfacial film. Compare and contrast various types of emulsifying agents Identify the methods and techniques employed in preparing of stable pharmaceutical emulsions. Identify the factors that affect the stability of emulsion, such as temperature and environmental conditions. Chapter 14| Disperse Systems : Emulsions Emulsions : Emulsion is a thermodynamically unstable disperse system consisting of two immiscible liquids, one of which is distributed throughout the other in minute globules (droplets). In emulsion terminology, the dispersed phase is the internal phase, and the dispersion medium is the external or continuous phase. Generally, to prepare a stable emulsion, a third phase, an emulsifying agent, is necessary. Chapter 14| Disperse Systems : Emulsions Chapter 14| Disperse Systems : Emulsions Chapter 14| Disperse Systems : Emulsions Emulsion Types 1. Oil-in-Water (o/w) Emulsions: In o/w emulsions, the internal phase consists of an oleaginous or oily component, dispersed within an aqueous external phase. Chapter 14| Disperse Systems : Emulsions 2. Water-in-Oil (w/o) Emulsions: In w/o emulsions, the internal phase consists of water or an aqueous component, dispersed within an oleaginous external phase. Because the external phase of an emulsion is continuous. An o/w emulsion may be diluted or extended with water or an aqueous preparation and a w/o emulsion, with an oleaginous or oil-miscible liquid. Chapter 14| Disperse Systems : Emulsions 3. Multiple emulsions: Multiple emulsions have multiple layers of dispersed and continuous phases, including both oil-in-waterin-oil (o/w/o) and water-inoil-in-water (w/o/w) structures. Chapter 14| Disperse Systems : Emulsions Chapter 14| Disperse Systems : Emulsions Macroemulsions vs. Microemulsions : Microemulsions can be formed spontaneously by agitating oil and water phases with carefully selected surfactants. The type of microemulsion produced depends on the properties of the oil and surfactants used. Microemulsions have significantly smaller droplets compared to macroemulsions, with diameters ranging from 100 Å to 1,000 Å. In contrast, macroemulsions have larger droplets, around 5,000 Å in diameter. Both o/w (oil-in-water) and w/o (water-in-oil) microemulsions can be formed based on the oil and surfactant properties. Chapter 14| Disperse Systems : Emulsions Microemulsions offer advantages in oral drug delivery, providing more rapid and efficient absorption compared to solid dosage forms. Microemulsions enhance transdermal drug delivery by facilitating increased diffusion into the skin. The small droplet size of microemulsions promotes efficient absorption through the skin barrier Chapter 14| Disperse Systems : Emulsions Chapter 14| Disperse Systems : Emulsions Macroemulsion Microemulsion Size: around 5,000 Å Size: 100 Å to 1,000 Å White opaque appearance Cloudy Translucent Thermodynamically unstable Thermodynamically stable Requires a substantial input energy for production Forms spontaneously or Transparent Chapter 14| Disperse Systems : Emulsions Determination tests of the emulsion type : 1. Miscibility test o/w emulsion remain stable upon dilution with water, but will not remain homogenous upon addition of oil and vice versa 2. Staining test Addition of oil soluble stain to the emulsion of unknown type on a glass slide under microscope Staining globules and colorless medium= o/w emulsion Staining background and colorless globules = w/o emulsion Chapter 14| Disperse Systems : Emulsions Chapter 14| Disperse Systems : Emulsions 3. Conductivity test Water conduct electricity, hence an emulsion in which water forms the continuous phase acts as a conductor. Oil is a non-conductor and emulsion in which forms the external phase act as non-conductor. Chapter 14| Disperse Systems : Emulsions Classification of emulsions according to the physical state Emulsions can be formulated as: Liquid Semisolids According to the route of administration Based on the constituents and the intended application. Liquid emulsions may be employed: Orally: o/w for example, castor oil emulsion Topically: for example lotion Parenterally: (I.V. o/w ) (I.M. and S.C. may be w/o) Chapter 14| Disperse Systems : Emulsions Semisolid emulsions Topically: for examples, lotions, creams and liniments The choice between o/w and w/o emulsions depends on many factors such as: 1. The nature of therapeutic agents, 2. Desired effects, 3. The intended route of administration Chapter 14| Disperse Systems : Emulsions Chapter 14| Disperse Systems : Emulsions Purpose and Benefits of Emulsions Improved Drug Administration: Emulsification allows the pharmacist to create stable mixtures of two immiscible liquids, enabling the administration of a liquid drug in the form of minute globules (introducing of many ingredients in different phases as liquid dosage form). Chapter 14| Disperse Systems : Emulsions Orally administered emulsions, are always in the form of o/w emulsions. They can improve the palatability of drug administration by dispersing it in a sweetened, flavored aqueous vehicle (taste masking). o/w emulsion act as carrier for lipophilic drugs, enabling the oil soluble drug to dissolved in the dispersed phase and potentially enhance oral bioavailability Chapter 14| Disperse Systems : Emulsions Sterile I.V. o/w emulsions are used for administration of nutritive oil and oil soluble vitamins to the patients unable to ingest food. Intravenous emulsions must be o/w. Intramuscular and subcutaneous injections can be formulated as w/o emulsions. In such oily emulsions, the drug's effects are prolonged, as the drug must diffuse from the aqueous dispersed phase through the external oil phase to reach the tissue fluids. Chapter 14| Disperse Systems : Emulsions Emulsions for topical use can be either o/w or w/o, depending on the nature of therapeutic agents, the desired effects, and skin conditions. An o/w emulsion is more easily removed from the skin with water, making it suitable when easy removal is required. Medicinal agents that irritate the skin generally are less irritating in the internal phase of an emulsified topical preparation than in the external phase. Chapter 14| Disperse Systems :Emulsions w/o emulsions are more softening to the skin, resisting drying and removal by contact with water. The diminished particle size of the internal phase in emulsions can enhance percutaneous absorption (absorption through the skin), making them a valuable choice for dermatological formulations. Chapter 14| Disperse Systems :Emulsions The acceptable emulsion is characterized by the following: 1. The globules of dispersed phase must be remain uniformly distributed throughout the continuous phase 2. The formulation should have a pleasing appearance and texture 3. For oral administration, the flavor must be appropriate 4. For external application, the formulation must be easily spread over the affected area 5. Physically stable (shows no signs of flocculation, creaming, sedimentation and coalescence) 6. Absence of deterioration by microorganisms Chapter 14| Disperse Systems : Emulsions Disadvantages of emulsions 1. 1. Pharmaceutical emulsions, being thermodynamically unstable, require careful formulation to prevent the separation of their two phases. 2. Before measuring a dose, it is essential to shake the emulsion thoroughly. Even with efficient shaking, the accuracy of the dose is likely to be lower compared to solutions. 3. Storage conditions may affect the disperse system, potentially causing creaming or cracking 4. There is a possibility of microbial contamination, which can further lead to cracking issues 5. In comparison to solid dosage forms, liquid dosage forms, such as emulsions, tend to be more bulky Chapter 14| Disperse Systems :Emulsions Gibbs free energy in an emulsion : ΔG = ΔA γ A is the total surface area of dispersed particles γ is the interfacial tension , Stable emulsions must have a large “A” and a small “G” concurrently for consistent and uniform dosing. This is done by decreasing “γ,” which will decrease “G,” which will decrease self-attraction of dispersed phase particles Theories of Emulsification Chapter 14| Disperse Systems : Emulsions Theories of Emulsification There are many theories of emulsification: 1. Surface Tension Theory: All liquids tend to minimize their surface area by forming spherical shapes, which is the shape with the least surface area. Surface tension measures this tendency and is a force that resists the formation of smaller droplets when two immiscible liquids come into contact. Chapter 14| Disperse Systems : Emulsions Emulsifying agents, often called surfactants or wetting agents, reduce interfacial tension and diminish the liquids' attraction to their own molecules (reducing the repellent force between the liquids and diminishing each liquid's attraction for its own molecules). This theory suggests that emulsifiers lower the interfacial tension between immiscible liquids, thus, the surfaceactive agents facilitate the breaking up of large globules into smaller ones, which then have a lesser tendency to reunite or coalesce Chapter 14| Disperse Systems : Emulsions 2. Oriented-Wedge Theory: This theory is based on the idea that emulsifying agents form monomolecular layers around the droplets of the internal phase. The theory is based on the assumption that certain emulsifying agents orient themselves about and within a liquid in a manner reflective of their solubility in that particular liquid. Chapter 14| Disperse Systems : Emulsions In a system containing two immiscible liquids, probably the emulsifying agent is preferentially soluble in one of the phases and is embedded more deeply in that phase than the other. Because many molecules of substances have a hydrophilic or water-loving portion and a hydrophobic or waterhating portion, the molecules position or orient themselves into each phase. Emulsifying agents with a greater hydrophilic character tend to promote o/w emulsions, while those with a more hydrophobic character favor w/o emulsions. The phase in which the emulsifier is more soluble becomes the continuous phase of the emulsion. Chapter 14| Disperse Systems :Emulsions 3. Plastic or Interfacial Film Theory: This theory places emulsifying agents at the interface between the immiscible liquids, forming a thin film adsorbed on the surface of internal phase droplets. The film acts as a barrier, preventing contact and coalescence of the dispersed phase. The stability of the emulsion depends on the toughness and flexibility of this film. The degree of solubility of the emulsifying agent in the two phases determines whether o/w or w/o emulsions are formed. Chapter 14| Disperse Systems : Emulsions Chapter 14| Disperse Systems : Emulsions Preparation of Emulsions Factors Affecting Emulsion Formation: The stability and characteristics of an emulsion are influenced by the following factors: Emulsifying agents pH The ratio of internal to external phases. The success of emulsions depends on the careful selection of emulsifying agents and understanding their properties. The initial step in preparation of an emulsion is selection of the emulsifier. Chapter 14| Disperse Systems : Emulsions Criteria for Selecting Emulsifying Agents: 1. Compatibility: Emulsifying agents must be compatible with other formulation ingredients and should not interfere with the stability or efficacy of the therapeutic agent. 2. Stability: Emulsifying agents should be stable and not deteriorate during the preparation or storage of the pharmaceutical product. Chapter 14| Disperse Systems : Emulsions 3. Safety : Emulsifiers should be nontoxic and safe for consumption by the patient, and they should possess minimal odor, taste, or color. 4. Promotion of Emulsification: A crucial role of emulsifying agents is to promote emulsification, ensuring that the two immiscible phases are dispersed effectively. Chapter 14| Disperse Systems : Emulsions Chapter 14| Disperse Systems : Emulsions Common Types of Emulsifying Agents 1. Carbohydrate Materials: Naturally occurring agents like acacia, tragacanth, agar, chondrus, and pectin are used. These materials form hydrophilic colloids. They typically form o/w emulsions. Acacia is often used in extemporaneous emulsions. Chapter 14| Disperse Systems : Emulsions Tragacanth and agar are commonly employed as thickening agents in acacia-emulsified products. Microcrystalline cellulose is employed in a number of commercial emulsions as a viscosity regulator. 2. Protein Substances: Gelatin, egg yolk, and casein are examples of protein-based emulsifiers that produce o/w emulsions. Gelatin, while effective, can lead to emulsions that become more fluid over time. Chapter 14| Disperse Systems : Emulsions 3. Molecular Weight Alcohols: Substances like stearyl alcohol, cetyl alcohol, and glyceryl monostearate are primarily used as thickening agents and stabilizers for o/w emulsions in external applications. Cholesterol and cholesterol derivatives may also be employed in externally used emulsions to promote w/o emulsions Chapter 14| Disperse Systems : Emulsions 4. Wetting Agents : These agents can be anionic, cationic, or nonionic and contain both hydrophilic and lipophilic groups. In anionic agents, the lipophilic portion is negatively charged, but in the cationic agent, it is positively charged. Anionic and cationic agents tend to neutralize each other and are considered incompatible, while nonionic emulsifiers show no inclination to ionize. Chapter 14| Disperse Systems :Emulsions Depending on their individual nature, certain members of these groups form o/w emulsions and others w/o emulsions. Anionic emulsifiers include various monovalent, polyvalent, Organic soaps, such as triethanolamine oleate, Sulfonates, such as sodium lauryl sulfate. Cationic emulsifier, such as Benzalkonium chloride (known primarily for its bactericidal properties) Nonionic emulsifiers, such as span and tween Chapter 14| Disperse Systems :Emulsions 5. Finely Divided Solids: Colloidal clays like bentonite, magnesium hydroxide, and aluminum hydroxide can form o/w emulsions when the insoluble material is added to the aqueous phase if there is a greater volume of the aqueous phase than of the oleaginous phase. If the powdered solid is added to the oil and the oleaginous phase volume predominates, a substance such as bentonite is capable of forming a w/o emulsion. The relative volume of internal and external phases is critical for their effectiveness. Chapter 14| Disperse Systems :Emulsions Auxiliary emulsifying agent Lipophilic High molecular Weight Alcohols Substances like stearyl alcohol, cetyl alcohol, and glyceryl monostearate are primarily used as thickening agents and stabilizers for o/w emulsions in external applications. Hydrophilic Tragacanth and agar are commonly used as thickening agents in acacia – emulsified products Chapter 14| Disperse Systems : Emulsions Type Mono-molecular Multi-molecular Example Potassium laureate Tween 80 Mechanism Coherent flexible film formed by SAA. (Lower interfacial tension) and stabilize the emulsion Acacia, Gelatin Strong rigid film formed mostly by hydrocolloids, which produce O/W emulsions. Stability due mainly to strength of interfacial film (forming a coherent multi-molecular film which is strong and prevent the coalescence) Chapter 14| Disperse Systems : Emulsions Type Solid particles Example Bentonite Magnesium hydroxide Mechanism Film formed by solid particles that are small in size compared to the droplets of the dispersed state Particles wetted by both phases to some extent in order to remain at the interface and form a stable film (form a particulate film that prevent the coalescence) HLB system Chapter 14| Disperse Systems :Emulsions Hydrophilic-Lipophilic Balance (HLB) System: Generally, each emulsifying agent has a hydrophilic portion and a lipophilic portion, with one or the other being more or less predominant and influencing in the manner already described the type of emulsion. A method has been devised whereby emulsifying or surface-active agents may be categorized on the basis of their chemical makeup as to their hydrophilic-lipophilic balance, or HLB. By this method, each agent is assigned an HLB value or number indicating the substance's polarity (the numbers have been assigned up to about 40). Chapter 14| Disperse Systems : Emulsions The usual range is between 1 and 20. Each surfactant have an HLB number representing the relative proportions of the lipophilic and hydrophilic parts of the molecule Materials that are highly polar or hydrophilic have been assigned higher numbers than materials that are less polar and more lipophilic. Materials with HLB values of 3 to 6 are highly lipophilic and favor waterinoil (w/o) emulsions. HLB values of about 8 to 18 correspond to emulsifying agents favoring oilin-water (o/w) emulsions. Chapter 14| Disperse Systems : Emulsions Chapter 14| Disperse Systems : Emulsions Activity Assigned HLB Anti foaming 1-3 Emulsifiers (W/O) 3-6 Wetting agents 7-9 Emulsifiers (O/W) 8-18 Solubilizers 15-20 detergents 13-16 Chapter 14| Disperse Systems : Emulsions Required HLB : To ensure emulsion stability, it is necessary to select emulsifying agents having the same or nearly the same HLB value as the oleaginous phase of the intended emulsion. Certain emulsifying agents of a given HLB value appear to work best with a particular oil phase and this has given rise to the concept required HLB value for any oil or combination of oils. All oils, waxes and other materials likely to be incorporated into emulsions have an individual "Required HLB." Chapter 14| Disperse Systems : Emulsions For example, mineral oil has an assigned HLB value of 4 if a w/o emulsion is desired and a value of 10.5 if an o/w emulsion is to be prepared. To prepare a stable emulsion, the emulsifying agent should have a required HLB value similar to the one for mineral oil, depending on the type of emulsion desired. Hydrophilic-lipophilic balance (HLB) method is used for calculating the relative quantities of SAA (emulgents) that necessary for producing a physically stable emulsion. Chapter 14| Disperse Systems : Emulsions Blending Emulsifying Agents and Calculations in the HLB System: Stability is achieved by selecting emulsifying agents with HLB values similar to the intended emulsion. Combining two or more emulsifiers may be necessary to achieve the required HLB value. HLB values are additive, allowing the blending of surfactants to achieve the desired total HLB value. Chapter 14| Disperse Systems : Emulsions The HLB of a mixture of surfactants, for example, a mixture consisting of A and B surfactants Total =1 If fraction A = x Then fraction B = 1-X Total HLB= fraction A ( x) + fraction B (1 - x) Chapter 14| Disperse Systems : Emulsions Calculation the HLB for a mixture of surfactants is assumed to be an algebraic summation of the two HLB numbers: 1. Multiply the HLB of each surfactant by its fraction. 2. Add the obtained values to get the total HLB Total HLB = HLBA ( X) + HLBB (1-X) Chapter 14| Disperse Systems : Emulsions Example: In the Blending two surfactants, what is the ratio of each surfactant? Surfactant A with an HLB value of 8.0, surfactant B with an HLB value of 12.0 to achieve a total HLB value of 9.0. If fraction A = x Then fraction B = 1-X Total HLB = HLBA ( X) + HLBB (1-X) 9 = 8( X) + 12(1-X) Fraction A = X= 0.75 Fraction B =1-X = 1- 0.75 =0.25 ( 3: 1) Chapter 14| Disperse Systems : Emulsions Example: A formulator is required to formulate an o/w emulsion of the basic formula : Liquid paraffin 50 g Emulsifying agents (required HLB 10.5) 5 g Water to 100 g Calculate the fraction of Tween 80 (HLB of 15) and Span 80 (HLB of 4.3) used to produce a physically stable liquid paraffin emulsion. Chapter 14| Disperse Systems : Emulsions If fraction of tween 80 =X Then fraction of span 80 =1-X HLB mixture = HLBA ( X) + HLBB (1-X) 10.5 =15 * (x) + 4.3 *(1-x) X=0.58 fraction of A ( tween 80) 1-0.58=0.42 fraction of B ( span 80) 0.58* 5 g = 2.9 g of tween 80 0.42 * 5 g = 2.1 g of span 80 Chapter 14| Disperse Systems : Emulsions Example: o/w Emulsion Liquid petrolatum (Required HLB 10.5) 50 g Emulsifying agents 5 g Sorbitan monooleate (HLB 4.3) Polyoxyethylene 20 sorbitan monoleate (HLB 15.0) Water, qs 100 g By simple algebra, it can be shown that 4.5 parts by weight of sorbitan monooleate blended with 6.2 parts by weight of polyoxyethylene 20 sorbitan monooleate will result in a mixed emulsifying agent having the required HLB of 10.5. Chapter 14| Disperse Systems : Emulsions Because the formula calls for 5 g, the required weights are 2.1 and 2.9 g, respectively. The oil-soluble sorbitan monooleate is dissolved in the oil and heated to 75°; the water-soluble polyoxyethylene 20 sorbitan monooleate is added to the aqueous phase that is heated to 70°. At this point, the oil phase is mixed with the aqueous phase and the whole is stirred continuously until cool. The formulator is not restricted to these two agents to produce a blend with an HLB of 10.5. There are various proportions required, using other pairs of emulsifying agents, Chapter 14| Disperse Systems : Emulsions Preparation Methods Chapter 14| Disperse Systems : Emulsions Preparation Methods Various methods are employed for emulsion preparation, ranging from smallscale laboratory techniques to large-scale industrial processes. Each method has its advantages and is chosen based on the nature of components and desired emulsion characteristics Chapter 14| Disperse Systems : Emulsions Small-Scale Emulsion Preparation Methods Laboratory Equipment: Small-scale emulsions can be prepared using equipment like: 1. Dry Wedgwood or porcelain mortar and pestle, 2. Mechanical blenders such as milkshake mixers, hand homogenizers, or 3. Simple prescription bottles. Chapter 14| Disperse Systems : Emulsions Chapter 14| Disperse Systems : Emulsions Laboratory Techniques: In the small-scale extemporaneous preparation of emulsions, three methods may be used. They are: 1. The continental or dry gum method 2. The English or wet gum method 3. The bottle or Forbes bottle method Chapter 14| Disperse Systems :Emulsions The continental or dry gum method: The continental or dry gum method involves triturating the emulsifying agent (e.g., acacia) with oil before adding water (addition of external phase to the internal phase). The continental method is also referred to as the 4:2:1 method because for every four parts by volume of oil, two parts of water and one part of gum are added in preparing the initial or primary emulsion. For instance, if 40 mL of oil is to be emulsified, 20 mL of water and 10 g of gum would be employed in the primary emulsion. Chapter 14| Disperse Systems :Emulsions In this method, the acacia or other o/w emulsifier is triturated with the oil in a perfectly dry Wedgwood or porcelain mortar until thoroughly mixed. After the oil and gum have been mixed, the two parts of water are added all at once, and the mixture is triturated immediately, rapidly, and continuously until the primary emulsion is formed. A mortar with a rough rather than smooth inner surface must be used to ensure proper grinding action and reduction of the globule size. Chapter 14| Disperse Systems :Emulsions A glass mortar is too smooth to produce the proper reduction of the internal phase. The emulsion is transferred to a graduate and made to volume with water previously swirled about in the mortar to remove the last portion of emulsion. Chapter 14| Disperse Systems :Emulsions English or Wet Gum Method: The English or wet gum method creates a mucilage of the emulsifying agent with water before slowly incorporating oil (addition of internal phase to the external phase). By this method, the same proportions of oil, water, and gum are used as in the continental or dry gum method, but the order of mixing is different. A mucilage of the gum is prepared by triturating in a mortar granular acacia with twice its weight of water. Chapter 14| Disperse Systems :Emulsions The oil is then added slowly in portions, and the mixture is triturated to emulsify the oil. After all of the oil has been added, the mixture is thoroughly mixed for several minutes to ensure uniformity. Then, the other formulative materials are added, and the emulsion is transferred to a graduate and brought to volume with water. Chapter 14| Disperse Systems :Emulsions Bottle or Forbes bottle method: The bottle or Forbes bottle method is suitable for volatile oils or oleaginous substances of low viscosities, involving shaking the mixture in a capped bottle. Powdered acacia is placed in a dry bottle, two parts of oil are added, and the mixture is thoroughly shaken in the capped container. Chapter 14| Disperse Systems :Emulsions A volume of water approximately equal to that of the oil is then added in portions and the mixture thoroughly shaken after each addition. When all of the water has been added, the primary emulsion thus formed may be diluted to the proper volume with water or an aqueous solution of other formulative agents Chapter 14| Disperse Systems : Emulsions Important considerations on emulsion preparation : Prior to mixing, all the water soluble ingredients are dissolved in the aqueous phase and all the oil-soluble components are dissolved in the oil Solid substances such as preservatives, stabilizers, colorants, and any flavoring material are usually dissolved in a suitable volume of water (assuming water is the external phase) and added as a solution to the primary emulsion. Chapter 14| Disperse Systems : Emulsions If fats waxes or SAA that are solids or semisolid at room temperature are needed, warm the two phases, the aqueous phase temperature is raised 2-3C° above that of oil phase, so that no local crystallization of waxes takes place upon mixing of the two phases Any substances that might interfere with the stability of the emulsion or the emulsifying agent are added as near last as is practical. Chapter 14| Disperse Systems : Emulsions Alcohol has a precipitating action on gums such as acacia, thus no alcohol or solution containing alcohol should be added directly to the primary emulsion, because the total alcoholic concentration of the mixture would be greater at that point than after other diluents were added. When all necessary agents have been added, the emulsion is transferred to a graduate and made to volume with water previously swirled about in the mortar to remove the last portion of emulsion. Chapter 14| Disperse Systems : Emulsions Forbes bottle method is not suited for viscous oils because they cannot be thoroughly agitated in the bottle when mixed with the emulsifying agent. When the intended dispersed phase is a mixture of fixed oil and volatile oil, the dry gum method is generally employed Chapter 14| Disperse Systems : Emulsions Auxiliary Methods: An emulsion prepared by either the wet gum or the dry gum method 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 orifice that reduces the globules of the internal phase to about 5 j.lm and sometimes less. The hand homogenizer is less efficient in reducing the particle size of very thick emulsions. Chapter 14| Disperse Systems : Emulsions In Situ Soap Method (Nascent soap method): The two types of soaps developed by this method are calcium soaps 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 simply by mixing equal volumes of the oil and limewater. Chapter 14| Disperse Systems : Emulsions The emulsifying agent in this instance is the calcium salt of the free fatty acid formed from the combination of the two entities. In the case of olive oil, the free fatty acid is oleic acid, and the resultant emulsifying agent is calcium oleate. Large-scale preparation : On a larger scale, mixing tanks equipped with high-speed impellers are used for emulsion formation. - Colloid mills or large homogenizers may be employed to refine the emulsion further. Industrial homogenizers have the capacity to handle as much as 100,000 L of product per hour. Chapter 14| Disperse Systems : Emulsions Stability of Emulsion Chapter 14| Disperse Systems : Emulsions Stability of Emulsions The instability of emulsions can be categorized as follows: 1. Flocculation 2. Creaming or sedimentation 3. Coalescence or aggregation 4. Cracking or breaking 5. Phase separation Chapter 14| Disperse Systems : Emulsions Flocculation This process refers to aggregation or joining droplets together (without any change in primary droplet size) to form a large units or clumps ( floccules) which rise or settle in the emulsion depending on their densities. Chapter 14| Disperse Systems : Emulsions Good emulsion - Flocculation Chapter 14| Disperse Systems : Emulsions Creaming Aggregates of globules of the internal phase have a greater tendency than do individual particles to rise to the top of the emulsion or fall to the bottom. Such a preparation of the globules is termed the creaming of the emulsion, it is a reversible process. Creamed emulsion can be restored to its original state by gentle agitation, if insufficient shaking is employed before each dose, improper dosage of the internal phase substance may result. Chapter 14| Disperse Systems : Emulsions According to the Stokes equation the rate of separation of the dispersed phase of an emulsion may be related to such factors: 1. The particle size of the dispersed phase, 2. The difference in density between the phases, 3. The viscosity of the external phase. Larger particle size, greater density difference, and lower viscosity increase the rate of creaming. Chapter 14| Disperse Systems : Emulsions Upward creaming takes place in unstable emulsions of the o/w or the w/o type in which the internal phase has a lesser density than the external phase. Downward creaming takes place in unstable emulsions in which the opposite is true Chapter 14| Disperse Systems : Emulsions Strategies for enhanced the stability: 1. The globule or particle size should be reduced as fine as is practically possible, 2. The density difference between the internal and external phases should be minimal, 3. The viscosity of the external phase should be reasonably high. Chapter 14| Disperse Systems : Emulsions Coalescence and Breaking (Cracking) : If the droplet contacts another droplet, coalescence will occur to produce a single droplet of greater diameter and, the surface area of the new droplet will be less than the surface areas of the two individual droplets. This process will continue until there is complete phase separation (i.e. two liquid layers occur). Chapter 14| Disperse Systems : Emulsions Separation of the internal phase from the emulsion is called breaking, and the emulsion is described as being cracked or broken. This is irreversible, because the protective sheath about the globules of the internal phase no longer exists. Coalescence If an emulsion has cracked it cannot be recovered or redispersed by shaking. Separation (Breaking ) Chapter 14| Disperse Systems : Emulsions Phase Inversion : It is the process of an exchange between the disperse phase and the medium. For example, an o/w emulsion may with time or change of conditions invert to a w/o emulsion (occurs when the dispersed phase exceed a theoretical maximum of 74% of the total volume). Chapter 14| Disperse Systems : Emulsions Inversion o/w emulsion w/o emulsiom Chapter 14| Disperse Systems : Emulsions Consideration for temperature, light, environmental factors and storage : Generally, care must be taken to protect emulsions against extremes of cold and heat. Freezing and thawing coarsen an emulsion and sometimes break it. Excessive heat has the same effect. The presence of light, air, and contaminating microorganisms can adversely affect the stability of an emulsion; appropriate formulative and packaging steps are usually taken to minimize such hazards to stability. Chapter 14| Disperse Systems : Emulsions For light-sensitive emulsions, light-resistant containers are used. For emulsions susceptible to oxidative decomposition, antioxidants may be included in the formulation and adequate label warning provided to ensure that the container is tightly closed to air after each use. Chapter 14| Disperse Systems : Emulsions Preservation of emulsion Many molds, yeasts, and bacteria can decompose the emulsifying agent, disrupting the system. Because fungi (molds and yeasts) are more likely to contaminate emulsions than are bacteria, fungistatic preservatives, commonly combinations of methylparaben and propylparaben, are generally included in the aqueous phase of an o/w emulsion. Alcohol in the amount of 12% to 15% based on the external phase volume is frequently added to oral o/w emulsions for preservation. Therapeutic examples Chapter 14| Disperse Systems : Emulsions Therapeutic examples of Oral and Topical Emulsions Oral Emulsions Mineral Oil Emulsion: Mineral oil emulsion, or liquid petrolatum emulsion, is an o/w emulsion prepared from the following materials: Mineral oil, acacia, syrup, vanillin, alcohol, and purified water. Preparation by the dry gum method (4:2:1). Used as a lubricating cathartic with enhanced palatability compared to plain mineral oil. Chapter 14| Disperse Systems : Emulsions Commercial variations may include additional cathartic agents. Castor Oil Emulsion: Indications: Laxative for constipation and colon preparation for diagnostic examinations. Simethicone Emulsion: Indications: Defoaming agent for relief of gastrointestinal gas symptoms. Chapter 14| Disperse Systems : Emulsions Topical Emulsions : Lotions Many hand and body lotions for dry skin are o/w emulsions. A number of topical emulsions, or lotions, are used therapeutically to deliver a drug systemically. An example is Estrasorb, which contains estradiol for menopausal symptom relief. Shampoos: Shampoos are solution, emulsion, or suspension dosage forms used for hair and scalp cleansing. Chapter 14| Disperse Systems : Emulsions Topical Emulsions : Liniments Liniments are alcoholic or oleaginous solutions or emulsions of various medicinal substances intended to be rubbed on the skin The vehicle for a liniment should therefore be selected for the type of action desired (rubefacient, counterirritant, or massage) and also on the solubility of the desired components in the various solvents. All liniments should bear a label indicating that they are suitable only for external use and must never be taken internally. Chapter 14| Disperse Systems : Emulsions Liniments that are emulsions or that contain insoluble matter must be shaken thoroughly before use to ensure even distribution of the dispersed phase, and these preparations should be labeled shake well. liniments are prepared in the same manner as solutions, emulsions, or suspensions